[Clinical characteristics and prognosis of seizures in 75 children with acute lymphoblastic leukemia].

OBJECTIVE: To investigate the clinical characteristics, treatment, and prognosis of seizures in children with acute lymphoblastic leukemia (ALL) during chemotherapy. METHODS: Children with ALL with seizures during chemotherapy admitted to the Department of Pediatrics, Peking University People's Hospital from January 2010 to March 2022 were retrospectively analyzed. Clinical data including the incidence of seizure, time at seizure onset, causes, management, and prognosis were collected retrospectively. RESULTS: A total of 932 children with ALL were admitted during the study period, of whom, 75 (8%) were complicated with seizures during the period of chemotherapy. There were 40 males and 35 females, with a median age of 7.5 (1-17) years, and 43 cases (57.3%) occurred within the first 2 months of chemotherapy. The underlying diseases were reversible posterior encephalopathy syndrome (n=15), cerebral hemorrhage (n=10, one of whom was complicated with venous sinus thrombosis), intrathecal or systemic methotrexate administration (n=11), brain abscess (n=7, fungal infection in 3 cases, and bacterial in 4), viral encephalitis (n=2), febrile seizure (n=7), hyponatremia (n=7), hypocalcemia (n=2), and unknown cause (n=14). Sixty-four children underwent neuroimaging examination after seizure occurrence, of whom 37 (57.8%) were abnormal. The electroencephalograhpy (EEG) was performed in 44 cases and was abnormal in 24 (54.4%). Fifty-five patients remained in long-term remission with regular chemotherapy, 8 patients received hematopoietic stem cell transplantation, 9 died and 3 lost to follow-up. Symptomatic epilepsy was diagnosed in 18 cases (24%), and was well controlled in 16 with over 1 year of seizure-free. Whereas 2 cases were refractory to anti-seizure medications. CONCLUSION: Seizures are relatively common in children with ALL, most commonly due to reversible posterior encephalopathy syndrome, methotrexate-related neurotoxicity, and cerebral hemorrhage. Seizures occurred within 2 months of chemotherapy in most cases. Neuroimaging and EEG should be performed as soon as possible after the first seizure onset to identify the etiology and to improve the treatment regimen. Some cases developed symptomatic epilepsy, with a satisfactory outcome of seizure remission mostly after concurrent antiseizure medication therapy.

Effects of ciprofol for the induction of general anesthesia in patients scheduled for elective surgery compared to propofol: a phase 3, multicenter, randomized, double-blind, comparative study.

OBJECTIVE: Ciprofol is a newly developed intravenous sedative-hypnotic drug. The objective of the study was to prove whether ciprofol was non-inferior to propofol for the successful induction of general anesthesia. The ideal post-induction sedation level was assessed by comparing patients' clinical symptoms and their hemodynamic effects in responding to noxious stimuli, mostly tracheal intubation and bispectral index (BIS) alterations following ciprofol/propofol administration. PATIENTS AND METHODS: In this multi-center, randomized, double-blind phase 3 trial, selective surgery patients were randomly assigned in a 1:1 ratio to either ciprofol 0.4 mg/kg (n = 88) or propofol 2.0 mg/kg (n = 88) groups. The primary endpoint was the percentage of patients with successful anesthesia inductions. Secondary endpoints included the times to successful induction of general anesthesia and loss of the eyelash reflex, changes in BIS, as well as safety indicators. RESULTS: The anesthesia induction success rates for both ciprofol 0.4 mg/kg and propofol 2 mg/kg groups were 100.0%, with a 95% CI lower success limit of -4.18% difference between the two groups, indicating that ciprofol was non-inferior to propofol. For secondary outcomes, the average time to successful anesthesia and loss of the eyelash reflex were 0.91 min and 0.80 min for ciprofol and 0.80 min and 0.71 min for propofol, respectively. The pattern of BIS changes with ciprofol was similar to propofol and stable during the anesthesia maintenance period. Safety was comparable with 88.6% TEAEs in the ciprofol group compared to 95.5% in the propofol group. The incidence of injection pain was significantly lower in the ciprofol group compared to the propofol group (6.8% vs. 20.5%, p < 0.05). In addition, the patients treated with ciprofol had a lesser increase in blood pressure and heart rate, and fewer cases with BIS > 60 within 15 min of intravenous administration, which indicated that ciprofol may provide a better ideal sedation level during the post-induction period under an equivalent dosing regimen to propofol. CONCLUSIONS: Ciprofol for patients undergoing selective surgery is a new option for the induction of general anesthesia.

[Chimeric antigen receptors T cells for treatment of 48 relapsed or refractory acute lymphoblastic leukemia children: long term follow-up outcomes].

Objective: To evaluate the safety and efficacy of chimeric antigen receptors T cells (CAR-T) in childhood acute B lymphoblastic leukemia (B-ALL) to probe the prognosis-related factors. Methods: Forty-eight children, 29 boys and 19 girls, aged 3-17years old (median age was 8 years old) , with recurrent or refractory CD19 positive B-ALL, were treated by the CD19 specific CAR-T cells. A total of 48 cases received 61 infusions. Flow cytometry or real-time quantitative polymerase chain reaction method were used to monitor micro residual disease (MRD) . The follow-up period was from 16 to 1 259 days with the median follow-up of 406 days. SPSS software was used to statistical analysis. Results: No adverse reaction was observed during 61 infusions. The most common adverse reaction after CAR-T cell infusions was cytokine-release syndrome (CRS) . Only 2 cases experienced level 3 CRS performance, including continuous high fever, convulsions, delirium, serous cavity effusion, and decreasing of blood pressure. Tocilizumab was given to release CRS performance. No treatment-related death occurred. Thirty-seven patients showed response during 7 to 28 days after infusions. The early response rate was 77.1%, with MRD before infusion less than 5% group higher than the MRD more than 5% group (87.1% vs 58.8%, χ2=4.968, P=0.036) . For the 37 patients who showed response to CAR-T cell infusions, univariate analysis identified that age, disease status at the time of treatment, MRD before infusion affected 2-year OS rate (P<0.05) . Multivariate prognostic analysis for EFS disclosed that the MRD before infusion more than 5% (RR=3.433, 95% CI 1.333-8.844, P=0.011) and not bridge to HSCT (RR=4.996, 95% CI 1.852-13.474, P=0.001) were the independent risk factors. Conclusion: The fourth generation CAR-T cells directed against CD19 could effectively and safely treat relapsed and refractory B-ALL, which implicated that CAR-T therapy as a novel therapeutic approach could be useful for patients with relapsed or refractory B-ALL who have failed all other treatment options. Reducing MRD as far as possible by effective pretreatment chemotherapy was in favor of increasing the response rate. Bridging HSCT after CAR-T cell treatment might be a better therapeutic strategy for the patient with refractory or molecular relapsed B-ALL.

[Study of clinical outcome and prognosis in pediatric core binding factor-acute myeloid leukemia].

Objective: To analyze the clinical outcome and the prognostic factor in pediatric patients with core binding factor-acute myeloid leukemia (CBF-AML). Methods: A total of 121 newly diagnosed pediatric CBF-AML patients enrolled from Aug. 2005 to Sep. 2017 were retrospectively reviewed. Cumulative incidence of relapse (CIR), event-free survival (EFS) and overall survival (OS) rates were estimated by Kaplan-Meier method and prognostic factors were evaluated by Cox regression with SPSS. Results: Of the 121 patients, 120 patients were assessed for bone marrow remission after induction chemotherapy. 100 cases (83.3%) achieved complete remission (CR) after the first course of chemotherapy. 119 cases (99.2%) achieved CR after the second course of chemotherapy. Of the 121 patients, 13 patients (10.7%) had recurrence with the median interval of recurrence as 13.8 months (3.7 to 58.8 months). 17 patients (14.0%) died. The CIR, EFS and OS at 3 years were 12.7%, 77.5% and 82.8%, respectively. The factors including age at diagnosis, sex, initial WBC count, presence of extramedullary leukemia, C-KIT expression, additional chromosomal abnormalities, and CR after the first course of chemotherapy were analyzed by multivariate regression analysis of Cox. Multivariate analysis identified that additional chromosomal abnormalities was the only independent risk factor affecting OS (HR=4.289, 95%CI 1.070-17.183, P=0.040). Conclusions: Pediatric CBF-AML was a unique setting of prognostic subtypes. Chemotherapy produced good responses. Additional chromosomal abnormalities was the only independent risk factor for OS in pediatric CBF-AML.

Amplitude of Low Frequency Fluctuation (ALFF) study of the spontaneous brain activities of patients with phantom limb pain.

OBJECTIVE: Our objective was to use Amplitude of Low-Frequency Fluctuation (ALFF) method to investigate the changes in spontaneous brain activity in HM patients and their relationships with clinical features. PATIENTS AND METHODS: This study was set out to observe, using Functional magnetic resonance imaging (fMRI), the changes in spontaneous brain activity in patients with phantom limb pain (PLP). Eleven amputees with PLP closely matched in age, sex, and education in a right side lower limb were scanned using fMRI to measure the amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) in the resting state of the brain (GPLP) before use of prosthetic. They were then scanned again after recovering from PLP (GPLPr) after use of artificial limbs. Eleven healthy volunteers (GC) were also scanned. RESULTS: When compared to GC, GPLP exhibited decreased ALFF in the left inferior parietal lobule, and GPLPr exhibited decreased ALFF in the left precuneus. When compared to GPLP, GC showed positive FC in the part regions of the limbic system structure. When compared to GC, the positive FC in GPLPr was significantly decreased in the midbrain. Finally, when compared to GPLPr, GPLP showed significantly decreased positive FC in the right precuneus and inferior parietal lobe. The central nervous system shows functional changes in the resting state of the brain in patients with PLP, which may indicate the presence of neurobiological changes. The recovery time of the changes may be longer than the pain symptoms of patients. CONCLUSIONS: The technique of fMRI of the resting network of the brain in patients with PLP may be able to be used to monitor clinical therapeutic effects.

[Prognostic factors of pediatric patients with Ph-positive acute lymphoblastic leukemia].

Objective: To explore the clinical features and prognostic factors of Ph-positive and/or BCR-ABL positive acute lymphoblastic leukemia (Ph+ ALL) in children. Methods: The clinical data of 68 Ph+ ALL children who were treated at Peking University People's Hospital from December 2006 to December 2016 was retrospectively reviewed. Survival analysis were estimated by Kaplan-Meier method. Univariate analysis was estimated by Log-rank test and Chi-square, and multivariate analysis was estimated by Cox proportional hazards regression model. Results: In the 68 cases, the proportion of male to female was 2.1∶1, with a median age of 8 (1-16) years, and the median overall survival (OS) and disease free survival (DFS) were 16.8 months and 13.5 months, respectively. The early response rate to treatment was 43.9%, with myeloid-antigens-expression group lower than the non-expression group (29.6% vs 61.3%, χ2=5.814, P=0.020); The complete remission (CR) rate after one-course induction therapy was 86.2% (56/65), with good-response group higher than the poor-response group (100.0% vs 74.2%, χ2=6.680, P=0.003);The CR rate after induction in patients receiving imatinib plus chemotherapy was higher than the patients receiving chemotherapy only (94.9% vs 73.1%, χ2=5.185, P=0.024). The 2-and 5-year OS were (61.4±7.0)% and (50.8±8.1)%, respectively. The 2-and 5-year DFS were (54.6±6.8)% and (48.6±7.3)%, respectively. Univariate analysis showed that the initial WBC, LDH, spleen size, liver size, with-myeloid-antigens-expression, early response to treatment, MRD (BCR-ABL) after one-course induction, application of imatinib and different treatment options affected 2-year OS rate (all P<0.05). LDH, spleen size, liver size, with-myeloid-antigens-expression, early response to treatment, MRD (BCR-ABL) after one-course induction, application of imatinib and different treatment options affected 2-year DFS rate (all P<0.05). Multivariate prognostic analysis for OS (RR=45.7, 95% CI 1.4-1 528.2, P=0.033) and DFS (RR=52.3, 95% CI 1.6-1 725.9, P=0.026) showed that the spleen ≥ 3 cm was the independent risk factor. Conclusions: Pediatric Ph+ ALL is a special condition with unique clinical and biological features. The early response to treatment was poor in patients with myeloid-antigens-expression, which resulted in a low CR rate after one-course induction and the administration of imatinib can remarkably improve the CR rate. Initial spleen ≥ 3 cm is an independent prognostic factor. The efficacy of chemotherapy alone is poor, and imatinib combined with chemotherapy is applauded in the aim of improving outcomes.

[Application of general anesthesia combined with epidural anesthesia/analgesia in rehabilitation after gastric cancer resection].

Objective: To investigate the efficacy of general anesthesia with epidural anesthesia and postoperative epidural analgesia in terms of pain relief and post-operative functional recovery. Methods: Ninety-six patients were randomly assigned to general anesthesia and intravenous analgesia group (GI) or general anesthesia combined with epidural anesthesia and epidural analgesia group (GE). Demographic and operative data, postoperative VAS pain scores, gastrointestinal function, postoperative hospital stays, general complications were assessed prospectively. Results: (1) The postoperative VAS scores of patients in the group GE at 2, 24, 48, and 72 hours were significantly lower than those in the group GI. (2) Compared with the group GI, the patients in group GE had earlier postoperative flatus and a shorter postoperative hospital stay (8.4 ± 2.5 vs 10.0 ± 3.2, P=0.012 8). Conclusion: General anesthesia combined with epidural anesthesia and postoperative epidural analgesia could provide better pain relief, enhance early rehabilitation and reduce the duration of hospital.

[Thoracic paravertebral block in the PACU for immediate postoperative pain relief after video-assisted thoracoscopic surgery].

Objective: To investigate the effectiveness and safety of the thoracic paravertebral block(TPVB) in the post postanesthesia care unit(PACU) for patients suffered moderate to severe pain after Video-Assisted Thoracoscopic Surgery(VATS). Methods: 78 atients who complained moderate to severe pain on arrival to PACU after VATS were randomly assigned into two groups: thoracic paravertebral block treatment group(P group) and sufentanil treatment group(S group). The VAS Pain score at rest and movement, heart rate, blood pressure, and pulse oximetry 1 hour after treatment and duration of patients staying in the PACU after treatment were recorded. VAS Pain score at rest and on coughing at 8, 24 and 48 hours after treatment were closely monitored. Sufentanil comsumption, patient satisfaction and related complications were also recorded. Results: A successful TPVB was achieved in all patients in P group without puncture related complications. The VAS pain scores at rest and on coughing 1 hour, 8 hours, 24 hours and 48 hours after treatment in P group were significantly lower than the patients in S group. Systolic blood pressure 1 hour after treatment in P group was also lower than the patients in S group(118mmHg±14mmHg vs 128 mmHg±14 mmHg, P=0.021). SPO2 1 hour after treatment in P group was much higher than the patients in S group(95%±3% vs 92%±4%, P=0.015). The duration of patients staying in the PACU after treatment in both groups were similar. Sufentanil comsumption, rate of vomiting and nausea was significantly less and satisfaction was better in P group than thoses in S group. Conclusion: In the postanesthesia care unit, TPVB could provide effective and safe analgesia therapy for patients suffered from moderate to severe pain after VATS.

Reversal of graft steatosis after liver transplantation: prospective study.

OBJECTIVE: To determine the risk factors for reversal of liver graft steatosis. PATIENTS AND METHODS: This prospective study included 70 patients (47 men and 23 women) who received steatotic liver grafts between July 2003 and February 2008. No grafts from prisoners were used in the study. Patients were divided into 3 groups according to degree of liver steatosis, as follows: mild (n = 29, group 1), moderate (n = 23, group 2), and severe (n = 18, group 3). RESULTS: The median (SD) degree of steatosis in liver grafts at transplantation was 15.7% (7.3%) in group 1, 26.3% (10.5%) in group 2, and 45.1% (8.3%) in group 3. Postoperative histologic analysis demonstrated dramatically decreased steatosis in all graft recipients. CONCLUSION: Graft steatosis can be decreased substantially after liver transplantation. Factors for reversibility of steatosis include donor age, degree of macrovesicular steatosis, and cold ischemia time.

Experimental Sarcocystis hominis infection in a water buffalo (Bubalus bubalis).

A water buffalo (Bubalus bubalis) was fed 5.0 x 10(5) Sarcocystis hominis sporocysts from a human volunteer who had ingested S. hominis cysts from naturally infected cattle. A necropsy was performed on the buffalo 119 days after inoculation, and a large number of microscopic sarcocysts (approximately 5,000/g) were found in skeletal muscles. Ultrastructurally, the sarcocyst wall from buffalo muscles has upright villar protrusions measuring about 5.6 x 0.8 microm with numerous microtubules that run from the base to the apex. Sarcocysts from this buffalo were infective to 2 human volunteers, confirming their identity as S. hominis. Therefore, we believe that buffaloes can act experimentally as the intermediate host for S. hominis.

Identification of Sarcocystis hominis-like (Protozoa: Sarcocystidae) cyst in water buffalo (Bubalus bubalis) based on 18S rRNA gene sequences.

DNA templates were extracted from isolates of Sarcocystis hominis-like cysts collected from cattle and water buffalo, as well as from Sarcocystis fusiformis cysts and Sarcocystis suihominis cysts. The 18S rRNA genes were amplified using DNA from a single cyst as the templates. Approximately 1,367-1,440 bp sequences were obtained. The sequence difference in isolates of Sarcocystis hominis-like cysts from water buffaloes, and isolates of S. hominis cysts from cattle were very low, only about 0.1%, much lower than the lowest value (1.7%) among different species. Combined with their morphological structure, these sequence data indicate that the 4 isolates from cattle and water buffalo might be the same species, i.e., S. hominis, suggesting that both cattle and water buffalo may serve as the intermediate hosts for this parasite. Apparently, this is the first report using a single cyst to do such work and is a useful way to distinguish the Sarcocystis cyst in an intermediate host that may be simultaneously infected by several different Sarcocystis species.