Therapeutic efficacy and infectious complications of CD19-targeted chimeric antigen receptor-modified T cell immunotherapy.

Lymphocyte depletion chemotherapy CD19-targeted chimeric antigen receptor-modified T (CAR-T) cell immunotherapy is an innovative approach for the treatment of refractory or relapsed B-cell malignancies. This method also has the occurrence of infection, and there has been no systematic analysis of infectious complications. In our study, we intend to analyze the infection in patients between day 0 and day 90 by analyzing the data of 40 patients who received CD19 CAR-T cell therapy collected in our hospital. We assessed risk factors for infection before and after treatment using Poisson and Cox regression, respectively. A cohort study was used, including patients with acute lymphocytic leukemia, chronic lymphocytic leukemia and non-Hodgkin's lymphoma. 40 patients were infected for the first time occurred at a median of 6 days after CAR-T cell infusion, and 8 (20%) had 10 infections within 28 days after CAR-T cell infusion, on days 29 and 29. The infection density between 90 days was lower at 0.67. This resulted in an infection density of 1.19 infections per 100 days. Two patients (5%) developed invasive fungal infections and two patients (5%) developed life-threatening or fatal infections. In an adjusted model for baseline characteristics, patients with ALL, ≥4 prior antitumor regimens, and receiving the highest CAR-T cell dose had higher infection densities at 28 days. The incidence of infection was comparable to that observed in clinical trials of salvage associated with infection after CAR-T cell infusion.

[Applications and challenges of wearable electroencephalogram signals in depression recognition and personalized music intervention].

Rapid and accurate identification and effective non-drug intervention are the worldwide challenges in the field of depression. Electroencephalogram (EEG) signals contain rich quantitative markers of depression, but whole-brain EEG signals acquisition process is too complicated to be applied on a large-scale population. Based on the wearable frontal lobe EEG monitoring device developed by the authors' laboratory, this study discussed the application of wearable EEG signal in depression recognition and intervention. The technical principle of wearable EEG signals monitoring device and the commonly used wearable EEG devices were introduced. Key technologies for wearable EEG signals-based depression recognition and the existing technical limitations were reviewed and discussed. Finally, a closed-loop brain-computer music interface system for personalized depression intervention was proposed, and the technical challenges were further discussed. This review paper may contribute to the transformation of relevant theories and technologies from basic research to application, and further advance the process of depression screening and personalized intervention.

Signal Quality Investigation of a New Wearable Frontal Lobe EEG Device.

The demand for non-laboratory and long-term EEG acquisition in scientific and clinical applications has put forward new requirements for wearable EEG devices. In this paper, a new wearable frontal EEG device called Mindeep was proposed. A signal quality study was then conducted, which included simulated signal tests and signal quality comparison experiments. Simulated signals with different frequencies and amplitudes were used to test the stability of Mindeep's circuit, and the high correlation coefficients (>0.9) proved that Mindeep has a stable and reliable hardware circuit. The signal quality comparison experiment, between Mindeep and the gold standard device, Neuroscan, included three tasks: (1) resting; (2) auditory oddball; and (3) attention. In the resting state, the average normalized cross-correlation coefficients between EEG signals recorded by the two devices was around 0.72 ± 0.02, Berger effect was observed (p < 0.01), and the comparison results in the time and frequency domain illustrated the ability of Mindeep to record high-quality EEG signals. The significant differences between high tone and low tone in auditory event-related potential collected by Mindeep was observed in N2 and P2. The attention recognition accuracy of Mindeep achieved 71.12% and 74.76% based on EEG features and the XGBoost model in the two attention tasks, respectively, which were higher than that of Neuroscan (70.19% and 72.80%). The results validated the performance of Mindeep as a prefrontal EEG recording device, which has a wide range of potential applications in audiology, cognitive neuroscience, and daily requirements.

Recognition of Emotional States Using Multiscale Information Analysis of High Frequency EEG Oscillations.

Exploring the manifestation of emotion in electroencephalogram (EEG) signals is helpful for improving the accuracy of emotion recognition. This paper introduced the novel features based on the multiscale information analysis (MIA) of EEG signals for distinguishing emotional states in four dimensions based on Russell's circumplex model. The algorithms were applied to extract features on the DEAP database, which included multiscale EEG complexity index in the time domain, and ensemble empirical mode decomposition enhanced energy and fuzzy entropy in the frequency domain. The support vector machine and cross validation method were applied to assess classification accuracy. The classification performance of MIA methods (accuracy = 62.01%, precision = 62.03%, recall/sensitivity = 60.51%, and specificity = 82.80%) was much higher than classical methods (accuracy = 43.98%, precision = 43.81%, recall/sensitivity = 41.86%, and specificity = 70.50%), which extracted features contain similar energy based on a discrete wavelet transform, fractal dimension, and sample entropy. In this study, we found that emotion recognition is more associated with high frequency oscillations (51-100Hz) of EEG signals rather than low frequency oscillations (0.3-49Hz), and the significance of the frontal and temporal regions are higher than other regions. Such information has predictive power and may provide more insights into analyzing the multiscale information of high frequency oscillations in EEG signals.

Analysis and clinical characteristics of acute myeloid leukemia developing with prior or concurrent tumors in non cyto- or radiotherapy exposure patients in a single center.

ABSTRACTAcute myeloid leukemia (AML) that develops along with prior or concurrent tumors without previous cyto- or radiotherapy (pc-AML) is an essential subset of AML but is often ignored and ambiguous. The biological and genetic characteristics of pc-AML remain largely unknown. Moreover, it is unclear whether pc-AML should be treated as de novo or secondary AML, whereas most clinical trials exclude it due to comorbidities. We performed a retrospective study of 50 patients with multiple neoplasms over five years. We focused on characteristics, treatment regimens, response rate, and prognosis of pc-AML, compared with therapy-related AML (tAML) and AHD-AML (AML discovered following prior hematologic disorders) as controls. We report the first detailed distribution of secondary tumors associated with hematological disorders. The incidence of pc-AML was 30% of all multiple neoplasms, and it was predominantly found in male and older participants. Nearly three-quarters of gene mutations affected epigenetic regulation and signaling pathways, and NPM1, ZRSR2, and GATA2 occurred exclusively in pc-AML. No significant differences were in CR, and pc-AML had an inferior OS similar to that of tAML and AHD-AML. More patients received hypomethylation agents (HMAs) in combination with venetoclax (HMAs + VEN) than intensive chemotherapy (IC) (65.7% vs 31.4%), and there was a trend toward improved OS in HMAs + VEN-based than in IC-based patients, whose 2-year estimated OS times were 53.6% and 35.0%, respectively. In conclusion, our results collectively support pc-AML as a biologically and genetically distinct entity with high-risk and dismal outcomes, and HMAs in combination with venetoclax-based regimens may benefit patients with pc-AML.

Peripheral Blood Smears Distinguish Infective Fever after CAR-T Therapy.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy carries the risk of inducing severe and life-threatening toxicities such as cytokine release syndrome (CRS), neurotoxicity, and infection. Although CRS and infections have similar symptoms, their treatment strategies differ, and early diagnosis is very important. For CRS and infections, the fastest detection time currently takes more than 24 h, so a quick and simple method to identify a fever after CAR T-cell infusion is urgently needed. METHODS: We enrolled 27 patients with recurrent fever treated with different types of CAR T-cells, including cluster of differentiation (CD) 7, CD19, CD22, and CD19-CD22 bicistronic CAR T-cells, and evaluated the infection events occurring in these patients. We detailed the morphology of CAR T-cells in peripheral blood smears (PBS) and reported the infection events, CAR transgene copy number, and inflammatory indicators within the first month after treatment. RESULTS: Similar morphological characteristics were observed in the PBS of different CAR T-cells, namely, enlarged cell bodies, deep outside and shallow inside basophilic blue cytoplasm, and natural killer (NK) cell-like purplish red granules. There were ten infections in nine of the twenty-seven patients (33%). The percentage of atypical lymphocytes in PBS was significantly associated with CAR transgene copy number and absolute lymphocyte count in all patients. The atypical lymphocyte percentage was significantly higher in the non-infection group. CONCLUSIONS: In conclusion, the unique morphology of CAR T-cells in PBS can be used to evaluate CAR T-cell kinetics and provide reliable evidence for the rapid early identification of fever after CAR T-cell infusion. CLINICAL TRIAL REGISTRATIONS: ChiCTR-OPN-16008526; ChiCTR-OPN-16009847; ChiCTR2000038641; NCT05618041; NCT05388695.

[Efficacy of Activated Autologous Hematopoietic Stem Cell Transplantation in the Treatment of Acute Myeloid Leukemia].

OBJECTIVE: To compare the efficacy of activated autologous bone marrow and peripheral blood hematopoietic stem cell transplantation (Auto-HSCT) and matched sibling donor allogeneic hematopoietic stem cell transplantation (MSD-HSCT) for the first complete remission of adult acute myeloid leukemia (AML-CR1). METHODS: For 86 adult patients with first complete remission of AML who underwent auto-HSCT (41 cases) and MSD-HSCT (45 cases) in our hospital from June 2012 to June 2020, the patients were treated with modified MAC ï¼»Malflane 160 mg/(m2·d), -3 days, Ara-C 2 g/(m2·2), -3 days 21∶00, -2 days 9∶00, CTX 60 mg/(kg·d),-3 d, -2 dï¼½, the stem cells were activated by IL-2 (1 000 U/ mL), IFN-α (100 U/ mL) and IFN-γ (100 U/ml). The overall survival (OS), leukemia free survival (LFS), cumulative incidence of recurrence (CIR) and non-recurrence mortality (NRM) of patients with different types of transplantation were compared. RESULTS: The 3-year OS rates of Auto-HSCT group and MSD-HSCT group were 75% and 69.5%, and the 3-year LFS rates were 70.6% and 82.4%, respectively. There was no statisticaly significant difference in the 3-year OS rates of low risk, medium risk and high risk patients in the Auto-HSCT and MSD-HSCT group (90.2% vs 87.5%, 68.4% vs 68.8%, 28.6% vs 53.3%), the LFS rates of low risk, medium risk and high risk patients in the auto-HSCT and MSD-HSCT group were 90.2% and 87.5%(P=0.838), 71.8% and 91.7%(P=0.184), 0 and 67.5%(P=0.027), respectively. The NRM of Auto-HSCT and MSD-HSCT group were 4.9% and 20% (P=0.036), and CIR were 24.4% and 13.3% (P=0.188). Univariate analysis showed that the survival time of patients was significantly correlated with the number of CR courses and disease risk stratification (P=0.005, P=0.000). Cox multivariate analysis showed that disease risk stratification was an independent risk factor affecting OS (P=0.001). CONCLUSION: For adult patients with primary AML-CR1, Auto-HSCT is safe and effective. In the absence of sibling donor, Auto-HSCT can be regarded as an effective post-remission treatment for patients with intermediate risk AML-CR1.

Multidisciplinary recommendations for the management of CAR-T recipients in the post-COVID-19 pandemic era.

The outbreak of coronavirus disease 2019 (COVID-19) posed an unprecedented challenge on public health systems. Despite the measures put in place to contain it, COVID-19 is likely to continue experiencing sporadic outbreaks for some time, and individuals will remain susceptible to recurrent infections. Chimeric antigen receptor (CAR)-T recipients are characterized by durable B-cell aplasia, hypogammaglobulinemia and loss of T-cell diversity, which lead to an increased proportion of severe/critical cases and a high mortality rate after COVID-19 infection. Thus, treatment decisions have become much more complex and require greater caution when considering CAR T-cell immunotherapy. Hence, we reviewed the current understanding of COVID-19 and reported clinical experience in the management of COVID-19 and CAR-T therapy. After a panel discussion, we proposed a rational procedure pertaining to CAR-T recipients with the aim of maximizing the benefit of CAR-T therapy in the post COVID-19 pandemic era.

Frontal EEG-Based Multi-Level Attention States Recognition Using Dynamical Complexity and Extreme Gradient Boosting.

Measuring and identifying the specific level of sustained attention during continuous tasks is essential in many applications, especially for avoiding the terrible consequences caused by reduced attention of people with special tasks. To this end, we recorded EEG signals from 42 subjects during the performance of a sustained attention task and obtained resting state and three levels of attentional states using the calibrated response time. EEG-based dynamical complexity features and Extreme Gradient Boosting (XGBoost) classifier were proposed as the classification model, Complexity-XGBoost, to distinguish multi-level attention states with improved accuracy. The maximum average accuracy of Complexity-XGBoost were 81.39 ± 1.47% for four attention levels, 80.42 ± 0.84% for three attention levels, and 95.36 ± 2.31% for two attention levels in 5-fold cross-validation. The proposed method is compared with other models of traditional EEG features and different classification algorithms, the results confirmed the effectiveness of the proposed method. We also found that the frontal EEG dynamical complexity measures were related to the changing process of response during sustained attention task. The proposed dynamical complexity approach could be helpful to recognize attention status during important tasks to improve safety and efficiency, and be useful for further brain-computer interaction research in clinical research or daily practice, such as the cognitive assessment or neural feedback treatment of individuals with attention deficit hyperactivity disorders, Alzheimer's disease, and other diseases which affect the sustained attention function.

ECSMP: A dataset on emotion, cognition, sleep, and multi-model physiological signals.

This paper described the collection of multi-modal physiological signals, which include electroencephalography, electrocardiograph (ECG), photoplethysmography, electrodermal activity, temperature, and accelerometer data, recorded from 89 healthy college students during resting state, the emotion induction and recovery, and a set of cognitive function assessment tasks. Emotion, sleep, cognition, depression, mood, and other factors were evaluated through different methods, and were included in this dataset. Six emotions (neutral, fear, sad, happy, anger, and disgust) were induced by movie clips. The cognitive functions such as sustained attention, response inhibition, working memory, and strategy use, were quantitatively measured by Cambridge neuropsychological test automatic battery. The sleep ECG was collected the night before the emotion-induction experiment, and the sleep quality was analysed based on the sleep ECG. After the experiment, the participants were required to fill in questionnaires to evaluate the emotion regulation strategies, depression score, recent mood, and sleep quality index. The database can not only be directly used for the research of emotion recognition on multi-modal physiological signals, but also can further explore the interactions between emotion, cognition, and sleep.

[The Prognostic Value of Early Relapse after Autologous Hematopoietic Stem Cell Transplantation in Newly Diagnosed Multiple Myeloma].

OBJECTIVE: To assess the impact of early relapse (ER) after autologous hematopoietic stem cell transplan-tation (AHSCT) on overall survival (OS) for multiple myeloma (MM) patients. METHODS: Clinical data of 37 patients with MM undergoing AHSCT in department of hematology of Shanxi Bethune Hospital from January 2012 to December 2017 were retrospectively analyzed. The effect of ER on OS of patients was analyzed. The effects of international staging system (ISS) staging, cytogenetics, pre-transplant efficacy, minimal residual disease, and age on OS of the patients were also analyzed respectively. RESULTS: Among the 37 patients, 13 cases (35.1%) had ER, and 24 cases (64.9%) had non-ER. 3 patients with ER had extramedullary disease, but none with non-ER showed extramedullary disease. More than or equal to very good partial rate (VGPR) in patients with ER and without ER were 3 cases (23.1%) and 15 cases (62.5%), respectively, and the curative effect of the former was significantly lower than that of the latter (P<0.05). The median follow-up time was 31 (12-96) months, and median OS time was 93 months in all the patients. The median survival time of patients with ER was 17 months, and the median progression free survival was 7 months, both were significantly shorter than 93 months and 38 months of patients with non-ER (P<0.05). Univariate analysis showed that the OS was affected by ER, cytogenetic abnormalities (FISH), and ≥VGPR before transplantation. Multivariate analysis showed that ER was an independent prognostic factor. CONCLUSION: The prognosis of patients with ER after AHSCT in newly diagnosed MM is poor. ER is an independent prognostic factor of survival.

[The comparative study of the effects between modified FLAG and CAG on relapsed or refractory acute myeloid leukemia].

OBJECTIVE: To investigate the efficacy and toxicity of modified FLAG and CAG on relapsed or refractory acute myeloid leukemia (AML). METHODS: Sixty-one patients with relapsed or refractory AML were divided into modified FLAG or CAG group. In modified FLAG group: G-CSF 200 µg·m⁻²·d⁻¹ on days 0-5; fludarabine 30 mg·m⁻²·d⁻¹ on days 1-5; Ara-C 1.0 g·m⁻²·d⁻¹ on days 1-5. In CAG group: Ara-C 10 mg·m⁻²·12 h⁻¹ on days 1-14, aclarubicin 20 mg/d on days 1-4, G-CSF 200 µg·m⁻²·d⁻¹ on days 0 1-14. RESULTS: The complete response (CR) rate was 43% (12/28) and the partial response (PR) rate 18% (5/28) with the overall response (OR) rate of 61% in modified FLAG group. CR rate was 21% (7/33) and PR rate 15% (5/33) with OR rate of 36% in CAG group. There was significant statistical difference between two groups (P<0.05). The main toxicities of these groups were myelosupression and infection. The infection rate was 68% (19/28) in modified FLAG group (twenty-two patients were treated in the sterile laminar flow ward duing neutropenic period), treatment related mortality (TRM) in modified FLAG group was 7%; The infection rate was 55% (18/33) in CAG group (no patient was treated in the sterile laminar flow ward), TRM in CAG group was 3%. There was no significant statistical difference in two groups (P>0.05). CONCLUSION: Modified FLAG was effective for relapsed or refractory AML. The supportive cares to strengthen infection-controlled measures and shorten the period of bone marrow suppression produced the additional effect. CAG regimen has low adverse reactions and could be individualized to elder or weak patients.