Clinical data of 15 primary central nervous system lymphoma (PCNSL) children aged ≤18 years admitted to our hospital between May 2013 to May 2023 were retrospectively analyzed. Our goal was to summarize the clinical features of children and investigate the therapeutic effect of a high-dose methotrexate (HD-MTX) based chemotherapy regimen on this disease. The male-to-female ratio was 2.7∶1, and the median age was 7.2 (2.3-16.4) years at diagnosis. The initial clinical symptoms were primarily cranial hypertension, with imaging findings revealing multiple lesions. Pediatric PCNSL with normal immune function has a favorable prognosis with HD-MTX-based chemotherapy. Patients with a stable disease can be treated with minimal or no maintenance. HD-MTX-based chemotherapy remains effective when the disease progresses or recurs after an initial course of non-HD-MTX-based chemotherapy.

Objective:To evaluate the efficacy and safety of CD30 antibody-drug conjugates (ADC) brentuximab vedotin (BV) combined with chemotherapy in children with refractory or relapsed classic Hodgkin′s lymphoma (R/R cHL).Methods:Clinical data (including age, gender, B symptoms, clinical stage, previous treatment, etc.) of the 10 R/R cHL children diagnosed and treated at Beijing Children′s Hospital Affiliated to Capital Medical University from October 2021 to August 2023 were analyzed retrospectively. According to the different intensity of chemotherapy drugs, the dose of BV applied in the same course of treatment was 1.8 mg/kg for BV applied once every 3 weeks, and 1.2 mg/kg for BV applied once every 2 weeks. All 10 patients received at least 2 cycles of BV combined with chemotherapy and were evaluated every 2 cycles. The patients were followed up until May 31, 2024. The infusion reactions and adverse reactions after treatment were recorded.Results:In all 10 patients, there were 7 males and 3 females, the age ranged from 5.3-16.9 years, and there were 6 cases of refractory and 4 cases of relapsed. There were 6 cases of nodular sclerosis type, 2 cases of mixed cell type, 1 case of lymphocyte-rich type, and 1 case of lymphodepletion type. There were 5 cases of stage Ⅳ and 5 cases of stage Ⅲ. Previous treatment was mainly chemotherapy, 4 cases received radiotherapy and 1 case received programmed cell death protein 1 (PD-1) antibody therapy. The follow-up time ranged from 9 to 27 months. A total of 43 courses with 49 doses of BV alone or combined with chemotherapy were recorded, and the number of courses was 2 to 10 times. All 10 children responded to the treatment, and 9 achieved complete remission. BV infusion was successfully completed in all cases. A total of 28 cases of grade 3 or above adverse events were recorded, mainly myelosuppression, all of which were related to chemotherapy and did not affect sequential treatment.Conclusion:Brentuximab vedotin has demonstrated efficacy and a tolerable safety profile in the treatment of refractory and relapsed CD30-positive Hodgkin′s lymphoma in children.

Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Objective:To evaluate the efficacy and safety of brentuximab vedotin (BV) combined with rituximab and attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma (cHL).Methods:A prospective, non-randomized, risk-assigned study. Clinical data (including age, gender, B symptoms, bulky disease, CD30 and Epstein-Barr virus-encoded RNA(EBER) expression, clinical stage, risk stratification, etc.) of 28 intermediate to high-risk cHL children diagnosed and treated at Beijing Children′s Hospital Affiliated to Capital Medical University from October 2022 to May 2024 were collected. Immuno-targeted combined with attenuated chemotherapy was administered based on risk stratification and early treatment response. The patients were followed up until May 1st, 2024. The infusion reactions and adverse reactions after treatment were recorded.Results:In all 28 patients, there were 22 males and 6 females, the age was 12 (5,16) years, 16 cases (57%) presented with bulky disease and 10 cases (36%) with B symptoms. The most common pathological type was nodular sclerosis (14 cases, 50%). There were 7 cases of stage Ⅱ, 14 cases of stage Ⅲ and 7 cases of stage Ⅳ according to the Ann Arbor staging system. There were 5 cases in the intermediate-risk group and 23 cases in the high-risk group. EBER was positive in 20 cases (71%) and negative in 6 cases (21%), and CD30 antigen was expressed in tumor cells of all enrolled children. Treatment duration: 5 cases (18%) received 4 courses of treatment, 21 cases (75%) received 6 courses of treatment, and 2 cases (7%) received 8 courses of treatment, 25 cases (89%) achieved complete metabolism response (CMR) through early assessment after 2 courses of chemotherapy. The CMR rates were 100% in intermediate-risk group and 87% (20/23) in high-risk group, respectively. Four patients (14%) finally received residual field radiotherapy. Toxicities included grade Ⅰ-Ⅱ myelosuppression, early infusion reaction and mild peripheral neuropathy, only one case of grade 3 adverse events was recorded and did not affect sequential treatment. At the end of treatment and 3 months of follow-up, the levels of IgA, IgG and IgM were all decreased compared with the baseline before chemotherapy, and the total B cell count began to be lower than the level before chemotherapy at the early stage of treatment (after 2 courses). The total B cell count monitored during treatment was 50 (0, 101)×10 6/L and was 12 (0, 25)×10 6/L at the end of treatment. The follow-up time was 6 (3, 13) months, all 28 children had event-free survival and all achieved complete remission. At 6 and 9 months of follow-up, IgA, IgG, IgM and total B cell counts returned to pre-chemotherapy baseline levels, respectively. Conclusion:BV combined with rituximab attenuated chemotherapy has demonstrated efficacy and a tolerable safety profile in the treatment of cHL in children, and significantly reduce radiation rate.

Objective:To analyze the clinicopathological features, treatment and prognosis of Epstein -Barr virus(EBV) positive diffuse large B cell lymphoma(DLBCL) in children, so as to improve the knowledge of pediatricians on this disease.Methods:The data of 6 cases of EBV positive DLBCL who were initially diagnosed and regularly treated in Beijing Children′s Hospital from January 2016 to December 2019 were collected, including basic information (gender, age, first symptom, and course of disease), pathological results [immunohistochemistry, EBV encoded RNA(EBER), latent membrane protein(LMP), and C- MYC gene], immune function, EBV index, treatment group, treatment plan and prognosis. Results:There were 4 males and 2 females, with the average age of 6.67 years.The uric acid was 266.2 μmol/L, lactic dehydrogenase(LDH) was 346.5 U/L at early stage, and 1 patient had immunodeficiency.The immune function test before chemotherapy indicated that the proportion of auxiliary T cells decreased in 4 cases, and the humoral immune function was normal in all patients.There was no evidence of recent infection in 6 patients, and EBV-DNA increased in 3 patients.There were 2 cases of stage Ⅲ, 4 cases of stage Ⅳ, 1 case of giant tumor, 2 cases of symptom B, 6 cases of extranodal invasion, 4 cases of central invasion and 1 case of bone marrow invasion.Three patients died and three survived.Immunohistochemistry showed that: (1) CD 19, CD 20, and CD 79a were expressed in all patients, and CD 30 was expressed in 5 patients.(2) C- MYC gene was detected by immunofluorescence in situ hybridization method in all patients, and no MYC break, Bcl-2 and Bcl-6 break and amplification were found.(3) EBV: EBER and LMP-1 were expressed in all patients. Conclusions:The pathological changes of EBV positive DLBCL are similar to those adults.The origin of non-germinal center and extranodal and central invasion are more common.The prognosis of the patients with central nervous system invasion is very poor, and the recurrence and progress of the disease often occur in the treatment or in the early stage of drug withdrawal.At present, there is no effective and feasible treatment plan.It is suggested that the patients in the late stage should receive allogeneic hematopoietic stem cell transplantation as soon as possible after intensive treatment, so as to improve the survival rate.

Objective:To investigate the effect of serum cystatin C level on the occurrence and its long-term prognosis of contrast agent-induced acute kidney injury(CI-AKI)after percutaneous coronary intervention(PCI)in elderly patients.Methods:A total of 848 elderly patients(≥60 years)undergoing PCI in our department between Mar 2015 and Dec 2017 were enrolled in a prospective cohort.The CI-AKI was defined as the increase of serum creatinine ≥44.2 μmol/L within 48-72 h after using iodine contrast agent or more than 25 % higher than base level within 48-72 h after PCI.A receiver operating characteristic curve was used to analyze the optimal cut-off value of Cystatin C for predicting CI-AKI after PCI.Patients were divided into 2 groups based on the optimal cut-off value of Cystatin C: the high Cystatin C group(Cystatin C ≥1.3 mg/L, n=178)and the control group(Cystatin C<1.3 mg/L, n=670). The differences in the incidence of CI-AKI after PCI and major adverse cardiac events(MACE)at 1 year follow-up were compared between the two groups.The Cox regression model was further used to analyze the predictors of the long-term prognosis after PCI.Results:Of 848 patients receiving PCI, the incidence of CI-AKI was 9.4%.The incidence of MACE at 1 year after PCI was higher in the high Cystatin C group than in the control group(15.7% vs.9.3%, χ2=6.524, P=0.011). Cox regression analysis confirmed that the high baseline level of Cystatin C was the most independent predictive factor for MACE at 1 year of follow-up( HR=16.244, P<0.001). Conclusions:The high baseline level of Cystatin C(≥1.3 mg/L)is an independent risk factor for CI-AKI and is also the most important predictor for the occurrence of long-term MACE in elderly patients undergoing PCI.

Mechanical ventilation is an important supportive treatment for acute respiratory distress syndrome (ARDS). However, improper mechanical ventilation can cause a "second hit" to the lung, that is, ventilator-induced lung injury (VILI), characterized by translocation of pulmonary inflammatory mediators into the bloodstream, aggravating systemic inflammatory response syndrome, and multiple organ failure. Although the current protective mechanical ventilation strategy plays an important role in supporting treatment, the mortality of ARDS with mechanical ventilation is still very high. Therefore, to explore the strategy of pulmonary protective ventilation has always been the key orientation of ARDS and has important clinical significance. This article reviews the application, advantages and disadvantages of assisted and non-assisted spontaneous respiration in ARDS patients undergoing mechanical ventilation, in order to provide a reference for research and development of new strategies for ARDS protective ventilation.

Objective:To investigate the feasibility, clinical efficacy and safety of endobronchial ultasound (EBUS) in children.Methods:The radiological features, EBUS images, pathological results and intraoperative and postoperative complications of 3 cases who underwent EBUS examination and 1 case who underwent EBUS guided transbronchial needle aspiration (EBUS-TBNA) were retrospectively analyzed.Results:Among the 4 cases, 2 were males and 2 were females, with the onset age of 7.4-9.2 years. The child who underwent successful EBUS-TBNA was presented with fever and diagnosed with mediastinal lymphadenopathy before the operation, and the postoperative pathology indicated histiocytic necrotic lymphadenitis (HNL). The other 3 children diagnosed with primary airway tumors, whose pre-operative CT imaging found no infiltration in extra-bronchial structures, had the masses resected through EBUS. According to postoperative pathological findings, two were diagnosed with mucoepidermoid carcinoma and one with bronchial leiomyoma. The lesions were located at the opening of the right main bronchus in 1 case and at the main airway in 2 cases. EBUS showed abnormal echogenicity of the tracheal wall in the 3 cases, including hyperechoic area in the water capsule and mucous layer, relatively hypoechoic area in the submucosal smooth muscle layer, hyperechoic area in the inner cartilage layer, hypoechoic in the cartilage layer and hyperechoic in the outer cartilage layer. In one case, structural disorder of the submucosal smooth muscle layer and partial disruption of the cartilage layer of the tracheal wall were found at the lesion site, while the other 2 cases had intact tracheal wall structure. There were no postoperative complications such as pneumothorax or hemoptysis in the 4 children.Conclusion:EBUS is a safe and feasible technique for evaluating mediastinal lymph node enlargement and the degree of airway wall infiltration in primary airway tumor.

Objective:To investigate the clinical characteristics, treatment and prognosis of congenital pulmonary airway malformation (CPAM) complicated with chronic pulmonary aspergillosis (CPA) in children.Methods:The clinical manifestation, laboratory test, radiological feature, treatment and prognosis of 4 pediatric patients diagnosis of CPAM with CPA ascertained between March 2016 and April 2020 at the Department of No.2 Respiratory Medicine and Thoracic Surgery of Beijing Children′s Hospital were retrospectively analyzed.Results:The 4 children included 2 males and 2 females, their age ranged from 9.9 to 13.6 years. Cough presented in 3 cases, hemoptysis in 2 cases, whereas in 1 case, pneumothorax was the first manifestation of the condition. Past history revealed multiple hospital admissions for pneumonia in 2 children and 1 with more than 2 episodes of wheezing. Aspergillus IgG was positive in 3 patients. Significantly elevated total IgE and fumigatus-specific IgE levels were noted in 2 children. CT demonstrated multiple cystic lesions, and fungal balls were seen in 2 children. They all underwent lobectomy and the lung tissue from the 4 children all demonstrated CPAM with Aspergillus infection. Aspergillus fumigatus was isolated from the abscess collected during operation in 1 patient. Postoperative, voriconazole was given in 3 children for 8 weeks, recurrence was observed in 2 children with characteristics of allergic bronchopulmonary aspergillosis. Voriconazole was given in one patient for 12 weeks with no recurrence.Conclusions:CPAM might be complicated with CPA,if there are hemoptysis, and fungal ball in chest CT, cautious preoperative examinations for microorganism are necessary. The necessity and duration of postoperative antifungal therapy need to be determined on individual basis.

Objective: To summarize the clinical data of diffuse large B-cell lymphoma (DLBCL) in children and to evaluate the efficacy of Beijing Children′s Hospital B cell lymphoma protocol in the treatment of pediatric DLBCL. Methods: The data (clinical, pathology, lab and image data) of 46 pediatric DLBCL admitted to the treatment group of Beijing Children′s Hospital from January 2005 to June 2017 were collected and analyzed retrospectively. According to the risk factors of staging, existence of poor prognosis genes and giant tumors, stratified treatment was carried out according to the international standard modified LMB89 regimen with high dose and short course. The Kaplan-Meier method was used to calculate the event free survival (EFS) and the overall survival (OS). Results: (1) Among the 46 cases, there were 33 males and 13 females. The median age was 8.0 years. The time from the initial symptom onset to the diagnosis was more than 15 days in 45 children. Fourteen cases had B group symptoms (fever, night sweat, and weight lost), 25 cases had extranodal disease, 39 cases were stage Ⅲ and Ⅳ, 12 cases had bone marrow involvement, 3 cases had jawbone involvement. Thirty cases were group B and 16 cases were group C in the treatment group. (2) Initial symptoms: 6 cases had cervical mass, 20 cases had abdominal mass, 10 had abdominal pain with acute abdomen, 8 cases had fever, 2 cases had snore or upper respiratory tract obstruction. (3) Pathology result: 40 cases were germinal center B cell DLBCL, 6 cases were non germinal center B cell DLBCL, no case had the MYC gene rupture, double hit lymphoma and triple hit lymphoma. (4) Complication and evaluation: the tumor lysis syndrome was seen in 3 cases initially, severe infection and delayed treatment was seen in 1 case, no treatment related death. The first evaluation showed all cases were sensitive to chemotherapy (shrink>25%), the second evaluation showed 1 case had residual disease, the others were complete remission. (5) Treatment and outcome: the 5 year-EFS was the same with 5 year-OS, both were (97.8±2.2) %. Two cases relapsed after treatment off, early relapse was seen in 1 case, and died because of abandoning treatment. Late relapse was seen in 1 case and got a complete remission after Rituximab+group C protocol treatment. Conclusions Pediatric DLBCL was common in school aged boys, most cases were at middle and late stage at the time of diagnosis. DLBCL had a good prognosis after the treatment with Beijing Children′s Hospital′s B cell lymphoma protocol, but late relapse could be seen.