MS-20 enhances the gut microbiota-associated antitumor effects of anti-PD1 antibody.

Cancer immunotherapy has been regarded as a promising strategy for cancer therapy by blocking immune checkpoints and evoking immunity to fight cancer, but its efficacy seems to be heterogeneous among patients. Manipulating the gut microbiota is a potential strategy for enhancing the efficacy of immunotherapy. Here, we report that MS-20, also known as "Symbiota®", a postbiotic that comprises abundant microbial metabolites generated from a soybean-based medium fermented with multiple strains of probiotics and yeast, inhibited colon and lung cancer growth in combination with an anti-programmed cell death 1 (PD1) antibody in xenograft mouse models. Mechanistically, MS-20 remodeled the immunological tumor microenvironment by increasing effector CD8+ T cells and downregulating PD1 expression, which were mediated by the gut microbiota. Fecal microbiota transplantation (FMT) from mice receiving MS-20 treatment to recipient mice increased CD8+ T-cell infiltration into the tumor microenvironment and significantly improved antitumor activity when combined with anti-PD1 therapy. Notably, the abundance of Ruminococcus bromii, which increased following MS-20 treatment, was positively associated with a reduced tumor burden and CD8+ T-cell infiltration in vivo. Furthermore, an ex vivo study revealed that MS-20 could alter the composition of the microbiota in cancer patients, resulting in distinct metabolic pathways associated with favorable responses to immunotherapy. Overall, MS-20 could act as a promising adjuvant agent for enhancing the efficacy of immune checkpoint-mediated antitumor therapy.

Detecting Hydronephrosis Through Ultrasound Images Using State-of-the-Art Deep Learning Models.

The goal of this study was to assess the feasibility of three models for detecting hydronephrosis through ultrasound images using state-of-the-art deep learning algorithms. The diagnosis of hydronephrosis is challenging because of varying and non-specific presentations. With the characteristics of ready accessibility, no radiation exposure and repeated assessments, point-of-care ultrasound becomes a complementary diagnostic tool for hydronephrosis; however, inter-observer variability still exists after time-consuming training. Artificial intelligence has the potential to overcome the human limitations. A total of 3462 ultrasound frames for 97 patients with hydronephrosis confirmed by the expert nephrologists were included. One thousand six hundred twenty-eight ultrasound frames were also extracted from the 265 controls who had normal renal ultrasonography. We built three deep learning models based on U-Net, Res-UNet and UNet++ and compared their performance. We applied pre-processing techniques including wiping the background to lessen interference by YOLOv4 and standardizing image sizes. Also, post-processing techniques such as adding filter for filtering the small effusion areas were used. The Res-UNet algorithm had the best performance with an accuracy of 94.6% for moderate/severe hydronephrosis with substantial recall rate, specificity, precision, F1 measure and intersection over union. The Res-UNet algorithm has the best performance in detection of moderate/severe hydronephrosis. It would decrease variability among sonographers and improve efficiency under clinical conditions.

A siRNA targets and inhibits a broad range of SARS-CoV-2 infections including Delta variant.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has altered the trajectory of the COVID-19 pandemic and raised some uncertainty on the long-term efficiency of vaccine strategy. The development of new therapeutics against a wide range of SARS-CoV-2 variants is imperative. We, here, have designed an inhalable siRNA, C6G25S, which covers 99.8% of current SARS-CoV-2 variants and is capable of inhibiting dominant strains, including Alpha, Delta, Gamma, and Epsilon, at picomolar ranges of IC50 in vitro. Moreover, C6G25S could completely inhibit the production of infectious virions in lungs by prophylactic treatment, and decrease 96.2% of virions by cotreatment in K18-hACE2-transgenic mice, accompanied by a significant prevention of virus-associated extensive pulmonary alveolar damage, vascular thrombi, and immune cell infiltrations. Our data suggest that C6G25S provides an alternative and effective approach to combating the COVID-19 pandemic.

Increases in repolarization heterogeneity predict left ventricular systolic dysfunction and response to cardiac resynchronization therapy in patients with left bundle branch block.

INTRODUCTION: This study aimed to investigate the association between T-wave morphology and impaired left ventricular ejection fraction (LVEF) in patients with complete left bundle branch block (cLBBB), and the predictive value of T-wave morphology for response to cardiac resynchronization therapy (CRT). METHODS AND RESULTS: We enrolled 189 patients with cLBBB on electrocardiogram performed between January 2007 and December 2011 who underwent standard echocardiography. Repolarization parameters, including the QRS-to-T angle (TCRT), T-wave morphology dispersion (TMD), T-wave loop area (PL), and T-wave residuum (TWR), were reconstructed from digital standard 12-lead electrocardiograms by T-wave morphology analysis. CRT response was defined as ≥15% reduction in left ventricular end-systolic volume at 12 months after CRT implantation. The clinical outcome endpoint was a composite of heart failure hospitalization, heart transplantation, or death during follow up (mean, 5.8 years). On logistic regression, a higher heart rate, longer QRS duration, increased TMD, and larger TWR were all independently associated with LVEF < 40%. Among 40 patients who underwent CRT, those with a larger TMD (P = .007), larger PL (P = .025), and more negative TCRT (P = .015) had better response to CRT. A large TMD (P = .018) and large PL (P = .003) were also independent predictors of the clinical outcome endpoint. CONCLUSIONS: Increases in repolarization heterogeneity in patients with cLBBB are associated with impaired LVEF. A large TMD and large PL may be useful as additional predictors of response to CRT, improving patient selection for CRT.

Quality of audio-assisted versus video-assisted dispatcher-instructed bystander cardiopulmonary resuscitation: A systematic review and meta-analysis.

AIM: This study aimed to conduct a systematic review and meta-analysis comparing the effect of video-assistance and audio-assistance on quality of dispatcher-instructed cardiopulmonary resuscitation (DI-CPR) for bystanders. METHODS: Five databases were searched, including PubMed, Cochrane library, Embase, Scopus and NIH clinical trial, to find randomized control trials published before June 2017. Qualitative analysis and meta-analysis were undertaken to examine the difference between the quality of video-instructed and audio-instructed dispatcher-instructed bystander CPR. RESULTS: The database search yielded 929 records, resulting in the inclusion of 9 relevant articles in this study. Of these, 6 were included in the meta-analysis. Initiation of chest compressions was slower in the video-instructed group than in the audio-instructed group (median delay 31.5 s; 95% CI: 10.94-52.09). The difference in the number of chest compressions per minute between the groups was 19.9 (95% CI: 10.50-29.38) with significantly faster compressions in the video-instructed group than in the audio-instructed group (104.8 vs. 80.6). The odds ratio (OR) for correct hand positioning was 0.8 (95% CI: 0.53-1.30) when comparing the audio-instructed and video-instructed groups. The differences in chest compression depth (mm) and time to first ventilation (seconds) between the video-instructed group and audio-instructed group were 1.6 mm (95% CI: -8.75, 5.55) and 7.5 s (95% CI: -56.84, 71.80), respectively. CONCLUSIONS: Video-instructed DI-CPR significantly improved the chest compression rate compared to the audio-instructed method, and a trend for correctness of hand position was also observed. However, this method caused a delay in the commencement of bystander-initiated CPR in the simulation setting.

A CTLA-4 Antagonizing DNA Aptamer with Antitumor Effect.

The successful translation of cytotoxic T lymphocyte antigen-4 (CTLA-4) blockade has revolutionized the concept of cancer immunotherapy. Although monoclonal antibody therapeutics remain the mainstream in clinical practice, aptamers are synthetic oligonucleotides that encompass antibody-mimicking functions. Here, we report a novel high-affinity CTLA-4-antagonizing DNA aptamer (dissociation constant, 11.84 nM), aptCTLA-4, which was identified by cell-based SELEX and high-throughput sequencing. aptCTLA-4 is relatively stable in serum, promotes lymphocyte proliferation, and inhibits tumor growth in cell and animal models. Our study demonstrates the developmental pipeline of a functional CTLA-4-targeting aptamer and suggests a translational potential for aptCTLA-4.

A novel noninvasive surface ECG analysis using interlead QRS dispersion in arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: This study investigated the feasibility of using the precordial surface ECG lead interlead QRS dispersion (IQRSD) in the identification of abnormal ventricular substrate in arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS: Seventy-one consecutive patients were enrolled and reclassified into 4 groups: definite ARVC with epicardial ablation (Group 1), ARVC with ventricular tachycardia (VT, Group 2), idiopathic right ventricular outflow tract VT without ARVC (Group 3), and controls without VT (Group 4). IQRSD was quantified by the angular difference between the reconstruction vectors obtained from the QRS-loop decomposition, based on a principal component analysis (PCA). Electroanatomic mapping and simulated ECGs were used to investigate the relationship between QRS dispersion and abnormal substrate. RESULTS: The percentage of the QRS loop area in the Group 1-2 was smaller than the controls (P = 0.01). The IQRSD between V1-V2 could differentiate all VTs from control (P<0.01). Group 1-2 had a greater IQRSD than the Group 3-4 (V4-V5,P = 0.001), and Group 1 had a greater IQRSD than Group 3-4 (V6-Lead I, P<0.001). Both real and simulated data had a positive correlation between the maximal IQRSD (γ = 0.62) and the extent of corresponding abnormal substrate (γ = 0.71, both P<0.001). CONCLUSIONS: The IQRSD of the surface ECG precordial leads successfully differentiated ARVC from controls, and could be used as a noninvasive marker to identify the abnormal substrate and the status of ARVC patients who can benefit from epicardial ablation.

The use of a novel signal analysis to identify the origin of idiopathic right ventricular outflow tract ventricular tachycardia during sinus rhythm: Simultaneous amplitude frequency electrogram transformation mapping.

INTRODUCTION: The signal characteristics of intracardiac bipolar electrograms at the origin of idiopathic RVOT-VT during sinus rhythm remain unclear. OBJECTIVE: The study sought to develop a novel real-time/online technique, simultaneous amplitude frequency electrogram transformation (SAFE-T), to quantify and localize the diseased ventricular substrate in idiopathic RVOT-VT. METHODS: We retrospectively investigated the intracardiac bipolar recordings in 70 consecutive patients (26% male, mean age 42±12 years) who underwent successful radiofrequency catheter ablation of idiopathic RVOT-VT. We quantified the extent of the frequency fraction of ventricular potentials during sinus rhythm or ventricular pacing using a novel formula, the product of instantaneous amplitude and frequency, and showed that in a 3D geometry as an online SAFE-T map. RESULTS: The characteristics of the HHT spectra of electrograms derived from VT origins demonstrated high frequency components (>70 Hz), which were independent of the rhythm. The density of the abnormal potentials at the VT origins were higher (VT origins, 7.5±2.3 sites/cm2 vs. surrounding myocardium, 1.5±1.3 sites/cm2, p<0.001), and were significantly decreased after ablation (0.7±0.6 sites/cm2, p<0.001). A small region of abnormal potentials were observed in the VT origins (mean area of 1.5±0.8 cm2). The SAFE-T maps predicted the VT origins with 92% sensitivity, 78% specificity with optimal cut-off value of >3.0 Hz·mV. CONCLUSION: The online SAFE-T map was feasible for quantifying the diseased ventricular substrate, irrespective of the rhythm of activation, and can be used to identify the optimal ablation targets for idiopathic RVOT-VT. We found a limited region of abnormal potentials where the RVOT-VT origins were successfully ablated.

Probing the Fractal Pattern of Heartbeats in Drosophila Pupae by Visible Optical Recording System.

Judiciously tuning heart rates is critical for regular cardiovascular function. The fractal pattern of heartbeats - a multiscale regulation in instantaneous fluctuations - is well known for vertebrates. The most primitive heart system of the Drosophila provides a useful model to understand the evolutional origin of such a fractal pattern as well as the alterations of fractal pattern during diseased statuses. We developed a non-invasive visible optical heart rate recording system especially suitable for long-term recording by using principal component analysis (PCA) instead of fluorescence recording system to avoid the confounding effect from intense light irradiation. To deplete intracellular Ca(2+) levels, the expression of sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) was tissue-specifically knocked down. The SERCA group shows longer heart beat intervals (Mean ± SD: 1009.7 ± 151.6 ms) as compared to the control group (545.5 ± 45.4 ms, p < 0.001). The multiscale correlation of SERCA group (scaling exponent: 0.77 ± 0.07), on the other hand, is weaker than that of the control Drosophila (scaling exponent: 0.85 ± 0.03) (p = 0.016).

Significant treatment effect of adjunct music therapy to standard treatment on the positive, negative, and mood symptoms of schizophrenic patients: a meta-analysis.

BACKGROUND: Music therapy (MT) has been used as adjunct therapy for schizophrenia for decades. However, its role is still inconclusive. A recent meta-analysis demonstrated that MT for schizophrenic patients only significantly benefits negative symptoms and mood symptoms rather than positive symptoms. In addition, the association between specific characteristics of MT and the treatment effect remains unclear. The aim of this study was to update the published data and to explore the role of music therapy in adjunct treatment in schizophrenia with a thorough meta-analysis. METHODS: We compared the treatment effect in schizophrenic patients with standard treatment who did and did not receive adjunct MT through a meta-analysis, and investigated the clinical characteristics of MT through meta-regression. RESULTS: The main finding was that the treatment effect was significantly better in the patients who received adjunct MT than in those who did not, in negative symptoms, mood symptoms, and also positive symptoms (all p < 0.05). This significance did not change after dividing the patients into subgroups of different total duration of MT, amounts of sessions, or frequency of MT. Besides, the treatment effect on the general symptoms was significantly positively associated with the whole duration of illness, indicating that MT would be beneficial for schizophrenic patients with a chronic course. CONCLUSIONS: Our meta-analysis highlights a significantly better treatment effect in schizophrenic patients who received MT than in those who did not, especially in those with a chronic course, regardless of the duration, frequency, or amounts of sessions of MT. These findings provide evidence that clinicians should apply MT for schizophrenic patients to alleviate disease severity.

Benefits of Atrial Substrate Modification Guided by Electrogram Similarity and Phase Mapping Techniques to Eliminate Rotors and Focal Sources Versus Conventional Defragmentation in Persistent Atrial Fibrillation.

OBJECTIVES: This prospective study compared the efficacy of atrial substrate modification guided by a nonlinear phase mapping technique with that of conventional substrate ablation. BACKGROUND: The optimal ablation strategy for persistent atrial fibrillation (AF) was unknown. METHODS: In phase 1 study, we applied a cellular automation technique to simulate the electrical wave propagation to improve the phase mapping algorithm, involving analysis of high-similarity electrogram regions. In addition, we defined rotors and focal AF sources, using the physical parameters of the divergence and curvature forces. In phase 2 study, we enrolled 68 patients with persistent AF undergoing substrate modification into 2 groups, group-1 (n = 34) underwent similarity index (SI) and phase mapping techniques; group-2 (n = 34) received complex fractionated atrial electrogram ablation with commercially available software. Group-1 received real-time waveform similarity measurements in which a phase mapping algorithm was applied to localize the sources. We evaluated the single-procedure freedom from AF. RESULTS: In group-1, we identified an average of 2.6 ± 0.89 SI regions per chamber. These regions involved rotors and focal sources in 65% and 77% of patients in group-1, respectively. Group-1 patients had shorter ablation procedure times, higher termination rates, and significant reduction in AF recurrence compared to group-2 and a trend toward benefit for all atrial arrhythmias. Multivariate analysis showed that substrate mapping using nonlinear similarity and phase mapping was the independent predictor of freedom from AF recurrence (hazard ratio: 0.26; 95% confidence interval: 0.09 to 0.74; p = 0.01). CONCLUSIONS: Our study showed that for persistent AF ablation, a specified substrate modification guided by nonlinear phase mapping could eliminate localized re-entry and non-pulmonary focal sources after pulmonary vein isolation.

Novel application of a Wii remote to measure spasticity with the pendulum test: Proof of concept.

BACKGROUND: The pendulum test is a standard clinical test for quantifying the severity of spasticity. In the test, an electrogoniometer is typically used to measure the knee angular motion. The device is costly and difficult to set up such that the pendulum test is normally time consuming. OBJECTIVE: The goal of this study is to determine whether a Nintendo Wii remote can replace the electrogroniometer for reliable assessment of the angular motion of the knee in the pendulum test. METHODS: The pendulum test was performed in three control participants and 13 hemiplegic stroke patients using both a Wii remote and an electrogoniometer. The correlation coefficient and the Bland-Altman difference plot were used to compare the results obtained from the two devices. The Wilcoxon signed-rank test was used to compare the difference between hemiplegia-affected and nonaffected sides in the hemiplegic stroke patients. RESULTS: There was a fair to strong correlation between measurements from the Wii remote and the electrogoniometer (0.513

Static craniofacial measurements and dynamic airway collapse patterns associated with severe obstructive sleep apnoea: a sleep MRI study.

OBJECTIVES: Using sleep MRI, we aimed to identify static craniofacial measurements and dynamic upper airway collapse patterns associated with severe obstructive sleep apnoea (OSA) during natural sleep in age and BMI-matched patients. DESIGN: Nested case-control study. SETTING: Sleep MRI images (3.0 Tesla scanner) and synchronised acoustic recording were used to observe patterns of dynamic airway collapse in subjects with mild and severe OSA. Midsagittal images were also used for static craniofacial measurements. PARTICIPANTS: Fifteen male subjects with severe OSA (mean AHI 70.3 ± 23 events/h) were matched by age and BMI to 15 subjects with mild OSA (mean AHI 7.8 ± 1.4 events/h). Subjects were selected from a consecutive sleep MRI study cohort. MAIN OUTCOME MEASURES: Static craniofacial measurements selected a priori included measurements that represent maxillomandibular relationships and airway morphology. Axial, sagittal and coronal views of the airway were rated for dynamic collapse at retropalatal, retroglossal and lateral pharyngeal wall regions by blinded reviewers. Bivariate analysis was used to correlate measures associated with severity of OSA using AHI. Statistical significance was set at P < 0.01. RESULTS: Lateral pharyngeal wall collapse from dynamic sleep MRI (ß = 51.8, P < 0.001) and upper airway length from static MRI images (ß = 27.2, P < 0.001) positively correlated with severity of OSA. CONCLUSIONS: Lateral pharyngeal wall collapse and upper airway length are significantly associated with severe OSA based on sleep MRI. Assessment of these markers can be readily translated to routine clinical practice, and their identification may direct targeted surgical treatment.

Acoustic-integrated dynamic MR imaging for a patient with obstructive sleep apnea.

Obstructive sleep apnea syndrome (OSAS) is caused by multi-level upper airway obstruction. Anatomic changes at the sites of obstruction may modify the physical or acoustic properties of snores. The surgical success of OSA depends upon precise localization of obstructed levels. We present a case of OSAS who received simultaneous dynamic MRI and snore acoustic recordings. The synchronized image and acoustic information successfully characterize the sites of temporal obstruction during sleep-disordered breathing events.

Atypical neuroleptic malignant syndrome in patients treated with aripiprazole and clozapine: a case-series study and short review.

OBJECTIVES: Neuroleptic malignant syndrome (NMS) requires emergency treatment and can be fatal. Combined aripiprazole and clozapine therapy is rarely used in clinical settings, and NMS related this combination still lacks evaluation. Herein, we present two cases of atypical NMS treated with aripiprazole and clozapine. METHODS: Case 1 was a schizophrenic male with a history of NMS under treatment with aripiprazole 20 mg. He was hospitalized and maintained with aripiprazole 5 mg and clozapine 225 mg. On the 25th day, atypical NMS occurred with rigidity, elevated creatine kinase, and stupor, which subsided with supportive therapy. He was discharged under treatment with aripiprazole 15 mg and fluoxetine 60 mg. Case 2 was a female with schizoaffective disorder without a history of NMS. She was hospitalized and maintained with clozapine 50 mg and aripirazole 30 mg. On the 11th day, atypical NMS occurred with mild fever, delirium, and rigidity, which subsided under supportive therapy. RESULTS AND CONCLUSIONS: Our cases highlight the atypical features of NMS in patients being treated with combined ari-piprazole and clozapine. Consciousness change, modest elevation of creatine kinase, and leukocytosis were the most consistent findings; hyperthermia accounts for only some of the cases. This is a reminder of the importance of earlier detection of the soft signs and atypical features of NMS under this combined treatment.

Outlier-resilient complexity analysis of heartbeat dynamics.

Complexity in physiological outputs is believed to be a hallmark of healthy physiological control. How to accurately quantify the degree of complexity in physiological signals with outliers remains a major barrier for translating this novel concept of nonlinear dynamic theory to clinical practice. Here we propose a new approach to estimate the complexity in a signal by analyzing the irregularity of the sign time series of its coarse-grained time series at different time scales. Using surrogate data, we show that the method can reliably assess the complexity in noisy data while being highly resilient to outliers. We further apply this method to the analysis of human heartbeat recordings. Without removing any outliers due to ectopic beats, the method is able to detect a degradation of cardiac control in patients with congestive heart failure and a more degradation in critically ill patients whose life continuation relies on extracorporeal membrane oxygenator (ECMO). Moreover, the derived complexity measures can predict the mortality of ECMO patients. These results indicate that the proposed method may serve as a promising tool for monitoring cardiac function of patients in clinical settings.

A new method to derive fetal heart rate from maternal abdominal electrocardiogram: monitoring fetal heart rate during cesarean section.

BACKGROUND: Monitoring of fetal heart rate (FHR) is important during labor since it is a sensitive marker to obtain significant information about fetal condition. To take immediate response during cesarean section (CS), we noninvasively derive FHR from maternal abdominal ECG. METHODS: We recruited 17 pregnant women delivered by elective cesarean section, with abdominal ECG obtained before and during the entire CS. First, a QRS-template is created by averaging all the maternal ECG heart beats. Then, Hilbert transform was applied to QRS-template to generate the other basis which is orthogonal to the QRS-template. Second, maternal QRS, P and T waves were adaptively subtracted from the composited ECG. Third, Gabor transformation was applied to obtain time-frequency spectrogram of FHR. Heart rate variability (HRV) parameters including standard deviation of normal-to-normal intervals (SDNN), 0V, 1V, 2V derived from symbolic dynamics of HRV and SD1, SD2 derived from Poincareé plot. Three emphasized stages includes: (1) before anesthesia, (2) 5 minutes after anesthesia and (3) 5 minutes before CS delivery. RESULTS: FHRs were successfully derived from all maternal abdominal ECGs. FHR increased 5 minutes after anesthesia and 5 minutes before delivery. As for HRV parameters, SDNN increased both 5 minutes after anesthesia and 5 minutes before delivery (21.30±9.05 vs. 13.01±6.89, P < 0.001 and 22.88±12.01 vs. 13.01±6.89, P < 0.05). SD1 did not change during anesthesia, while SD2 increased significantly 5 minutes after anesthesia (27.92±12.28 vs. 16.18±10.01, P < 0.001) and both SD2 and 0V percentage increased significantly 5 minutes before delivery (30.54±15.88 vs. 16.18±10.01, P < 0.05; 0.39±0.14 vs. 0.30±0.13, P < 0.05). CONCLUSIONS: We developed a novel method to automatically derive FHR from maternal abdominal ECGs and proved that it is feasible during CS.

Synchronized imaging and acoustic analysis of the upper airway in patients with sleep-disordered breathing.

Progressive narrowing of the upper airway increases airflow resistance and can produce snoring sounds and apnea/hypopnea events associated with sleep-disordered breathing due to airway collapse. Recent studies have shown that acoustic properties during snoring can be altered with anatomic changes at the site of obstruction. To evaluate the instantaneous association between acoustic features of snoring and the anatomic sites of obstruction, a novel method was developed and applied in nine patients to extract the snoring sounds during sleep while performing dynamic magnetic resonance imaging (MRI). The degree of airway narrowing during the snoring events was then quantified by the collapse index (ratio of airway diameter preceding and during the events) and correlated with the synchronized acoustic features. A total of 201 snoring events (102 pure retropalatal and 99 combined retropalatal and retroglossal events) were recorded, and the collapse index as well as the soft tissue vibration time were significantly different between pure retropalatal (collapse index, 2 ± 11%; vibration time, 0.2 ± 0.3 s) and combined (retropalatal and retroglossal) snores (collapse index, 13 ± 7% [P ≤ 0.0001]; vibration time, 1.2 ± 0.7 s [P ≤ 0.0001]). The synchronized dynamic MRI and acoustic recordings successfully characterized the sites of obstruction and established the dynamic relationship between the anatomic site of obstruction and snoring acoustics.

Multi-scale symbolic entropy analysis provides prognostic prediction in patients receiving extracorporeal life support.

INTRODUCTION: Extracorporeal life support (ECLS) can temporarily support cardiopulmonary function, and is occasionally used in resuscitation. Multi-scale entropy (MSE) derived from heart rate variability (HRV) is a powerful tool in outcome prediction of patients with cardiovascular diseases. Multi-scale symbolic entropy analysis (MSsE), a new method derived from MSE, mitigates the effect of arrhythmia on analysis. The objective is to evaluate the prognostic value of MSsE in patients receiving ECLS. The primary outcome is death or urgent transplantation during the index admission. METHODS: Fifty-seven patients receiving ECLS less than 24 hours and 23 control subjects were enrolled. Digital 24-hour Holter electrocardiograms were recorded and three MSsE parameters (slope 5, Area 6-20, Area 6-40) associated with the multiscale correlation and complexity of heart beat fluctuation were calculated. RESULTS: Patients receiving ECLS had significantly lower value of slope 5, area 6 to 20, and area 6 to 40 than control subjects. During the follow-up period, 29 patients met primary outcome. Age, slope 5, Area 6 to 20, Area 6 to 40, acute physiology and chronic health evaluation II score, multiple organ dysfunction score (MODS), logistic organ dysfunction score (LODS), and myocardial infarction history were significantly associated with primary outcome. Slope 5 showed the greatest discriminatory power. In a net reclassification improvement model, slope 5 significantly improved the predictive power of LODS; Area 6 to 20 and Area 6 to 40 significantly improved the predictive power in MODS. In an integrated discrimination improvement model, slope 5 added significantly to the prediction power of each clinical parameter. Area 6 to 20 and Area 6 to 40 significantly improved the predictive power in sequential organ failure assessment. CONCLUSIONS: MSsE provides additional prognostic information in patients receiving ECLS.