Objective:To investigate the effect of pre-treatment plasma Epstein-Barr virus(EBV)DNA copy number on the clinical features and prognosis of patients with adult secondary hemophagocytic lymphohistiocytosis(sHLH).Methods:The clinical characteristics,survival rate,and prognostic factors of 171 patients with adult sHLH treated at Jiangsu Province Hospital from June 2017 to January 2022 were retrospectively analyzed in this study.Patients were divided into three groups,including the EBV DNA-negative group(＜5.0 × 102 copies/ml),lower EBV-DNA loads group(5.0 × 102-8.51 × 104 copies/ml),and higher EBV-DNA loads group(＞8.51 × 104 copies/ml),according to pre-treatment plasma EBV-DNA copy number.Cox regression model was established for screening prognostic factors.Adult sHLH survival prediction model was constructed and realized through the nomogram based on EBV-DNA load after adjusted the factors affecting survival of etiology and treatment strategy.Concordance index(C-index)and calibration curves were calculated to verify model predictive and discriminatory capacity.Results:Among 171 adult sHLH patients,84 patients were not infected with EBV(EBV DNA-negative group),and 87 with EBV(EBV DNA-positive group,48 lower EBV-DNA loads group and 39 higher EBV-DNA loads group).Consistent elevations in the levels of liver enzymes(ALT and AST),LDH,TG,β2-microglobulin and ferritin across the increasing of EBV-DNA load(all P＜0.05),while the levels of fibrinogen decrease(P＜0.001).The median follow-up time was 52 days(range 20-230 days),and 123 patients died.The overall survival(OS)rate of patients in EBV DNA-positive group was lower than that in EBV DNA-negative group(median OS:40 days vs 118 days,P＜0.001).Higher EBV-DNA loads had worse OS(median OS:24 days vs 45 days vs 118 days,P＜0.0001 for trend)compared to lower EBV-DNA loads and EBV DNA-negative group.Multivariate Cox analysis revealed that higher EBV-DNA loads(P=0.005),fibrinogen≤ 1.5 g/L(P=0.012),ferritin(P=0.041),associated lymphoma(P=0.002),and anti-tumor based strategy(P=0.001)were independent prognostic factors for OS.The C-indexes of 30 day,90 days,365 days survival rate were all greater than 0.8 of the nomogram model and calibration curves provided credibility to their predictive capability.Subgroup analysis showed that patients with higher EBV-DNA loads had a significantly worse prognosis in adult sHLH who were women,ferritin＞5 000 μg/L,β2-microglobulin＞7.4 mmol/L and regardless of age,etiologies,HScore points.Conclusion:The EBV-DNA load is a strong and independent predictor for survival in patients with sHLH.The prognostic nomogram based on EBV-DNA loads was dependable and provides a visual tool for evaluating the survival of adult sHLH.

OBJECTIVE: To investigate the expression and clinical significance of soluble Fas (sFas) and sFasL in patients with secondary hemophagocytic lymphohistiocytosis (sHLH). METHODS: From September 2015 to December 2020, 86 sHLH patients who met the HLH2004 diagnostic criteria were collected. They were divided into 55 cases in the MAHLH group and 31 cases in the NonMAHLH group according to the etiology. Thirty healthy persons were chosen as the normal control group, and 20 patients with systemic lupus erythematosus (SLE) were chosen as the disease control group. The expression levels of sFas and sFasL in the serum of patients with each group were detected by ELISA, and the clinical data were collected for statistical analysis. The significance of sFas and sFasL in sHLH was analyzed by ROC curve. RESULTS: Serum levels of sFas and sFasL in patients with newly diagnosed sHLH were significantly higher than those in disease control group and normal control group (P<0.01). The levels of sFas and sFasL in MAHLH group were significantly higher than those in nonMAHLH (infection related HLH and autoimmune disease related HLH) group (P<0.01). The serum levels of sFas and sFasL in 17 newly treated patients with sHLH (17/86) after treatment were significantly lower than those before treatment (P<0.01). The serum sFas level in newly diagnosed sHLH patients was positively correlated with SF(r=0.35), sCD25(r=0.79) and sFasL(r=0.73). The serum sFasL level was positively correlated with SF(r=0.39), sCD25(r=0.64) and sFas(r=0.73). Compared with the NonMAHLH group, the area under the ROC curve was 0.707 (95% CI: 0.593-0.821) (P=0.0015). The optimal critical value for diagnosing MAHLH by sFas level was 12 743 pg/ml, and the sensitivity and specificity were 70.9% and 71% respectively. Compared with the NonMAHLH group, the area under the ROC curve was 0.765(95% CI: 0.659-0.87)(P<0.01). The median OS time of sFas high expression group (≥16798.5 pg/ml) and sFasL high expression group (≥4 785 pg/ml) was significantly shorter than that of the low expression group (P<0.001). CONCLUSION Serum levels of sFas and sFasL can be used for the early diagnosis and differential diagnosis of sHLH disease, and are the factor related to the poor prognosis of sHLH.
Humans ; Lymphohistiocytosis, Hemophagocytic ; Clinical Relevance ; ROC Curve ; Sensitivity and Specificity ; Lupus Erythematosus, Systemic

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

BACKGROUND: With current chemotherapy treatment, >90% of survival has been obtained for Burkitt lymphoma (BL). In this study, the demographic characteristics and treatment outcomes are presented for 78 children in China with central nervous system-positive (CNS+) BL. METHODS: This retrospective study consecutively enrolled 78 CNS+ BL patients in Beijing Children's Hospital (BCH) from 2007 to 2019 who received the BCH B-cell non-Hodgkin's lymphoma regimen (modified by French-American-British mature lymphoma B-cell 96 [FAB/LMB96] C1 arm ± rituximab). Clinical characteristics, methods of disease detection in the CNS, and outcomes were evaluated. Univariate and multivariate analyses were used to assess prognostic factors. RESULTS: The median age of 65 boys and 13 girls at the time of diagnosis was 5.7 years (ranging from 1 to 14 years). Patients were followed up for a median time of 34 months (ranging from 1 to 72 months). Bone marrow invasion was found in 38 (48.7%) patients. There were 48 (61.5%), 44 (56.4%), and 25 (32%) patients with cranial nerve palsy, intracerebral mass (ICM), and para-meningeal extension, respectively. Abnormal cerebrospinal fluid (CSF) morphology and CSF immunophenotype appeared in 15 (19.2%) and 15 (19.2%) patients, respectively. There were 69 (88.5%) patients treated with chemotherapy combined with rituximab, and nine patients were treated solely with chemotherapy. Finally, five patients died of treatment-related infection, recurrence occurred for 13, and one developed a second tumor. The 3-year overall survival and event-free survival rates were 78.9% ± 4.7% and 71.4% ± 6.0%, respectively. Treatment with chemotherapy only, ICM positivity, and >4 organs involved at diagnosis were independent risk factors. CONCLUSIONS Rituximab combined with a modified LMB96 regimen has greatly increased the efficacy of treatment for Chinese children with CNS+ BL, and with the continuous collection of outcome data, treatment-related complications are decreasing. For further verification, a large sample multicentre randomized controlled study should be performed to explore a treatment scheme for Chinese children with even greater efficacy.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Central Nervous System ; Child ; Child, Preschool ; China ; Cyclophosphamide/therapeutic use* ; Disease-Free Survival ; Female ; Humans ; Infant ; Male ; Neoplasm Recurrence, Local ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

OBJECTIVE: To observe the expression of acidic mammalian chitinase(AMCase) in lung tissue of silicosis model rats, and bronchoalveolar lavage fluid(BALF) and serum of patients with occupational pneumoconiosis, and to evaluate the value of AMCase in the early diagnosis of pneumoconiosis. METHODS: i) The specific pathogen free adult male Wistar rats were randomly divided into control group and model group, with 15 rats in each group. The rats in the silicosis model group was exposed to free silica dust with a concentration of 2 000.0 mg/m~3 by dynamic inhalation for three hours a day, while the rats in control group were not exposed to dust. Five rats in the two groups were sacrificed at 4, 12 and 24 weeks after dust exposure. ii) By random number table method, a total of 191 patients with occupational pneumoconiosis who received large capacity lung lavage were selected as the pneumoconiosis group, 12 dust-exposed workers who received large capacity lung lavage were selected as the dust control group, and 200 healthy coal miners exposed to dust were selected as healthy control group. iii) Western blotting was used to detect the relative protein expression of AMCase, type Ⅰ collagen(COLⅠ), α-smooth muscle actin(α-SMA) in lung tissues of the rats and the relative protein expression of AMCase in human BALF. Enzyme linked immunosorbent assay was used to detect the level of AMCase protein in human serum. Receiver operating characteristic(ROC) curve was used to evaluate the value of AMCase protein level in human serum for early diagnosis of pneumoconiosis. RESULTS: The relative expression of AMCase, COLⅠand α-SMA protein in lung tissue of rats in the silicosis model group were higher than that of control group(all P<0.01). The relative expression of AMCase protein in BALF of pneumoconiosis group and pneumoconiosis stage Ⅰ, Ⅱ and Ⅲ subgroups were higher than that of dust control group(all P<0.05). The level of AMCase protein in serum of pneumoconiosis group and pneumoconiosis stage Ⅰ, Ⅱ and Ⅲ subgroups were higher than that of healthy control group(all P<0.05). The results of ROC curve analysis showed that the area under ROC curve was 0.78(95% confidence interval: 0.74-0.82).When the cut-off value of serum AMCase protein level was 466.0 ng/L, the sensitivity was 73.8%, and the specificity was 72.6%. CONCLUSION: AMCase protein in human serum has value for early diagnosis of pneumoconiosis and it could be a potential biomarker for early diagnosis of pneumoconiosis.

ObjectiveTo evaluate the effect of the integrated echinococcosis control program in Ningxia Hui Autonomous Region from 2011 to 2018. MethodsA package of integrated interventions were employed for echinococcosis control in 22 counties (districts) of Ningxia Hui Autonomous Region from 2011 to 2018, including screening of human echinococcosis, treatment of echinococcosis patients, deworming of domestic dogs and monitoring of infections, surveillance of echinococcosis in bovines and sheep, health education. The detection of human echinococcosis, seroprevalence of anti-Echinococcus antibody in children at ages of 6 to 12 years, the Echinococcus coproantigen-positive rate in domestic dogs, prevalence of echinococcosis in bovines and sheep, and the awareness of echinococcosis control knowledge were investigated and compared during the period between 2011 and 2018. Results The detection of human echinococcosis appeared a decline tendency in Ningxia Hui Autonomous Region over years during the period from 2011 to 2018 (χ²_trend = 82.22, P < 0.05), and the prevalence of human echinococcosis decreased from 0.31% in 2011 to 0.15% in 2018. The seroprevalence of anti-Echinococcus antibody appeared a decline tendency in children at ages of 6 to 12 years over years (χ²_trend = 439.64, P < 0.01), and the prevalence of anti-Echinococcus antibody decreased from 6.12% in 2011 to 0.67% in 2018. The Echinococcus coproantigen-positive rate appeared a decline tendency in domestic dogs over years (χ²_trend = 260.33, P < 0.05), and the prevalence of anti-Echinococcus antibody decreased from 7.11% in 2011 to 0.75% in 2018. The prevalence of bovine and sheep echinococcosis reduced from 3.26% and 5.08% in 2011 to 1.35% and 0.76% in 2018, and Echinococcus predominantly parasitized in bovine (92.00%) and sheep (93.94%) livers. A total of 63 stool samples were collected from red fox, wolf and badger in Xiji and Haiyuan counties of Ningxia Hui Autonomous Region in 2013 and 2014, with no Echinococcus coproantigen-positives detected, and 107 domestic cats and 3 domestic dogs were dissected in these two counties, with no Echinococcus found. A total of 6 046 wild mice were dissected in Xiji County, Yuanzhou District and Haiyuan County of Ningxia Hui Autonomous Region from 2016 to 2019, and the prevalence of E. multilocularis was 0.31%. The awareness of echinococcosis control knowledge appeared an increasing tendency in Ningxia Hui Autonomous Region over years from 2011 to 2018 (χ²_trend = 3 367.97, P < 0.01), and the awareness increased from 21.83% in 2011 to 72.24% in 2018. Conclusions The integrated echinococcosis control program achieves a remarkable effect in Ningxia Hui Autonomous Region, and the transmission of echinococcosis has been preliminarily controlled. However, the echinococcosis transmission risk remains in few regions, and the integrated echinococcosis control program remains to be reinforced.

Objective: To investigate the clinical characteristics of secondary hemophagocytic lymphohistiocytosis (sHLH) complicated with capillary leak syndrome (CLS) . Methods: The clinical and laboratory data of 87 sHLH patients, who were treated in our hospital between January 2015 and December 2017, were retrospectively analyzed. Depending on whether they were complicated with CLS, 21 sHLH patients were classified as the CLS-sHLH group, while 66 were classified as the non-CLS-sHLH group. The differences of clinical manifestations, laboratory tests, treatment and prognosis between the two groups were compared. Results: There was no significant difference in the etiology of sHLH between the CLS-sHLH group and the non-CLS-sHLH group (P>0.05) . The neutrophil, fibrinogen and albumin levels in the CLS-sHLH group were lower than those in the non-CLS-sHLH group, while the triacylglycerol levels were higher than those in the non-CLS-sHLH group (P<0.05) . Varying degrees of edema, weight gain, hypotension, hypoproteinemia, oliguria and multiple serous effusions were observed in the CLS-sHLH group. Among them, there were 15 patients that CLS get improved, and the medial time of improvement was 7 (5-14) days. The other 6 patients did not get remission, while they died within 6-30 days. The median overall survival of the CLS-sHLH group was lower than that of the non-CLS-sHLH group (75 days vs not reached, P=0.031) . Conclusions: There may be no correlation between the cause of sHLH and the occurrence of CLS. Severity of neutropenia, fibrinogen and albumin levels, and triglyceride levels may be accompanied for sHLH patients complicated with CLS. Patients with sHLH who complicated with CLS have a poor prognosis. Active treatment of HLH and its primary disease, reasonable fluid replacement and oxygen supply are crucial, which can effectively control disease progression.
Capillary Leak Syndrome ; Fibrinogen ; Humans ; Lymphohistiocytosis, Hemophagocytic ; Prognosis ; Retrospective Studies

Objective: To analyze the therapeutic effect of a modified LMB89 Group C regimen in the treatment of pediatric high-risk Burkitt lymphoma. Methods: The clinical data of 172 children with newly diagnosed high-risk Burkitt lymphoma from January 2007 to April 2017 were retrospectively analyzed. All the cases were treated with the modified LMB89 Group C regimen. Results: The median age of the patients was 6 (1-14) years. The sex ratio was 5.1∶1, 144 boys (83.7%) and 28 girls (16.3%) . According to St. Jude staging classification, 2 patients (1.2%) were in stage Ⅱ, 54 (31.4%) in stage Ⅲ and 116 (67.4%) in stage Ⅳ. Of them, 46 patients (26.7%) had mature B cell acute lymphoblastic leukemia (B-ALL) , and 52 patients had central nervous system (CNS) involvement. According to risk group, the patients can be divided into group C1 (CNS1, without testicles/ovaries involvement, n=65) , group C2 (CNS2, testicles/ovaries involvement, n=55) and group C3 (CNS3, n=52) . A total of 145 patients received rituximab combined with chemotherapy during the treatment, 10 patients suffered from progressive disease and died, and 5 patients relapsed. Treatment-related mortality was 2.9%. With a median follow-up of 36.0 (0.5-119.0) months, 3-year overall survival (OS) rate was (88.9±2.4) % and event free survival (EFS) rate was (87.9±2.6) % for all patients. 3-year EFS rates were (96.9±2.1) %, (90.9±3.9) % and (73.4±6.5) % for Group C1, C2 and C3 respectively, and that of Group C3 was significantly lower than that of Group C1 (χ(2)=12.939, P=0.001) and Group C2 (χ(2)=6.302, P=0.036) . The 3-year EFS rates were (79.3±6.8) % and (44.4±16.6) % for patients in group C3 treated with chemotherapy combined with rituximab and chemotherapy alone (χ(2)=5.972, P=0.015) . Multivariable Cox regression analysis showed that Stage Ⅳ (including B-ALL) , residual diseases in mid-term evaluation were independent unfavorable prognostic factors[HR=4.241 (95%CI 1.163-27.332) , P=0.026; HR=32.184 (95%CI 11.441-99.996) , P<0.001]. Conclusions: The modified LMB89 Group C regimen has ideal effect for the children with high-risk Burkitt lymphoma.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Humans ; Infant ; Male ; Prognosis ; Retrospective Studies

Humans ; Lymphohistiocytosis, Hemophagocytic ; Pleural Effusion

BACKGROUNDThe prevalence of sudden sensorineural hearing loss in children (CSSNHL) is consistently increasing. However, the pathology and prognosis of CSSNHL are still poorly understood. This retrospective study evaluated clinical characteristics and possible associated factors of CSSNHL.

METHODSOne hundred and thirty-six CSSNHL patients treated in Department of Otolaryngology-Head and Neck Surgery and Institute of Otolaryngology at Chinese PLA General Hospital between July 2008 and August 2015 were included in this study. These patients were analyzed for clinical characteristics, audiological characteristics, laboratory examinations, and prognostic factors.

RESULTSAmong the 136 patients (151 ears), 121 patients (121 ears, 80.1%) were diagnosed with unilaterally CSSNHL, and 15 patients (30 ears, 19.9%) with bilateral CSSNHL. The complete recovery rate of CSSNHL was 9.3%, and the overall recovery rate was 37.7%. We found that initial degree of hearing loss, onset of treatment, tinnitus, the ascending type audiogram, gender, side of hearing loss, the recorded auditory brainstem response (ABR), and distortion product otoacoustic emissions (DPOAEs) had prognostic significance. Age, ear fullness, and vertigo had no significant correlation with recovery. Furthermore, the relevant blood tests showed 30.8% of the children had abnormal white blood cell (WBC) counts, 22.1% had elevated homocysteine levels, 65.8% had high alkaline phosphatase (ALP), 33.8% had high IgE antibody levels, and 86.1% had positive cytomegalovirus (CMV) IgG antibodies.

CONCLUSIONSCSSNHL commonly occurs unilaterally and results in severe hearing loss. Initial severe hearing loss and bilateral hearing loss are negative prognostic factors for hearing recovery, while positive prognostic factors include tinnitus, gender, the ascending type audiogram, early treatment, identifiable ABR waves, and DPOAEs. Age, vertigo, and ear fullness are not correlated with the recovery. Some serologic indicators, including the level of WBC, platelet, homocysteine, ALP, positive CMV IgG antibody, fibrinogen, and some immunologic indicators, are closely related to CSSNHL.

Adolescent ; Child ; Child, Preschool ; Evoked Potentials, Auditory, Brain Stem ; Female ; Hearing Loss, Sensorineural ; blood ; etiology ; physiopathology ; Humans ; Male ; Otoacoustic Emissions, Spontaneous ; Retrospective Studies