Mining and Evaluation of Post-marketing Safe Alert Signals of Pegaspargase and L-asparaginase Based on BCPNN Method / 中国药房

OBJECTIVE： To mine and evaluate the post-marketing safety alert signals of pegaspargase （PEG-ASP） and L-asparaginase （L-ASP），and compare the safety differences between them ，so as to provide reference for clinical safe and rational drug use. METHODS ： The adverse drug event （ADE） reports of PEG-ASP and L-ASP issued by FDA adverse event reporting system from Jan. 1st，2004-Jun. 30th，2020 were retrieved. BCPNN method was used to mine the safety signals of these two drugs under the condition that the lower limit of information component （IC－2SD）＞0 and the number of events ≥3. The medium and strong signals of two drugs with IC －2SD≥1.5 were evaluated and compared in 8 system organ class，such as gastrointestinal system ，hepatobiliary system ，blood and lymphatic system ，blood vessels and lymphatic vessels ， nervous system ，immune system ，metabolism and nutrition ，various examinations. IC value of specific ADE signal and its 95％ confidence interval were analyzed by time scanning spectrum. RESULTS & CONCLUSIONS ：The reports of PEG-ASP and L-ASP as suspected drugs were 2 324 and 3 824；67 and 68 medium and strong signals were included ，respectively. In gastrointestinal system，the common strong signal of PEG-ASP and L-ASP was necrotic pancreatitis. In hepatobiliary system ，both of them showed strong signal in venoocclusive liver disease ，and this ADE was not included in the drug instruction. In blood and lymphatic system ， common strong signals of the two drugs were febrile neutropenia ，coagulation disorder ，neutropenia and febrile bone marrow regeneration disorder ；in blood vessels and lymphatic vessels ，in addition to haemodynamic instability ，IC values of other signals of L-ASP were higher than those of PEG-ASP. In nervous system ，IC values of other signals of L-ASP were higher than those of PEG-ASP except for intracranial haemorrhage. In immune system ，anaphylactic reaction was a medium signal for L-ASP but was a strong signal for PEG-ASP. In metabolism and nutritional diseases ，except for tumor lysis syndrome ，IC values of other signals of L-ASP were higher than those of PEG-ASP. The results of time scanning spectrum showed that the signals of necrotic pancreatitis and coagulation disorder of PEG-ASP were stable ，while the signals of veno occlusive liver disease and hypersensitivity were unstable and needed to be observed ；above four signals of L-ASP were stable signals. When using PEG-ASP or L-ASP clinically ， close attention should be paid to the safety problems such as hypersensitivity ，coagulation disorder ，thrombosis，necrotic pancreatitis，venoocclusive liver disease and hypoproteinemia.

Recovery time and risk factors of childhood coagulopathy caused by rodenticide poisoning / 中华实用儿科临床杂志

Objective@#To explore the recovery time and risk factors of coagulopathy caused by rodenticide poisoning through analyzing and following up the confirmed cases, and to provide more useful guidance information for the clinic practice.@*Methods@#A total of 96 cases with coagulation dysfunction caused by anticoagulant rodenticide poiso-ning in Children′s Hospital, Chongqing Medical University from January 2014 to December 2016, were analyzed retrospectively.The recovery time of coagulation function and the relationship between recovery time and drug involved way, dysfunction organs and poison concentration were studied respectively.@*Results@#(1) A total of 96 patients were hospitalized because of severe coagulopathy caused by the poisoning of second generation anticoagulant rodenticide.Brodifacoum was detected from 33 blood samples and the median concentration was 364 μg/L (55-4 654 μg/L). Bromadiolone was detected from 7 blood samples and the median concentration was 130 μg/L (18-652 μg/L). Brodifacoum and Bromadiolone were both detected from 8 cases and the median concentration was 741 μg/L (63-6 000 μg/L) and 11 μg/L (3-3 694 μg/L), respectively.(2) A total of 57 cases of the patients were successfully followed up.A total of 18 cases were confirmed with oral poisoning, 16 cases with dermal poisoning, while 23 cases denied any involved ways of poisoning, and 7 cases had organs dysfunction.The follow-up time was 12-54 months.All the hospitalized patients were given specific antidote Vitamin K treatment and recovered successfully without any sequelae.(3) The median recovery time of coagulopathy caused by rodenticide poisoning was 2.5 months.(4) The recovery time of coagulation function was positively correlated with the plasma concentration of Brodifacoum(r=0.619, P<0.01). (5) There was no significant correlation between recovery time and organ dysfunction or drug involved ways of poisoning involvement (all P>0.05).@*Conclusions@#The recovery time of coagulation dysfunction caused by anticoagulant rodenticide in children is much longer.The higher the concentration of Brodifacoum poison is, the longer the recovery time.Enough supplementation course of Vitamin K should be given according to the follow-up of coagulation function.

Clinical features and prognosis of central nervous system involvement in patients with Epstein -Barr virus associated hemophagocytic lymphohistiocytosis / 中华实用儿科临床杂志

Objective To investigate the clinical features and prognosis of central nervous system(CNS)in-volvement in Epstein-Barr virus(EBV)associated hemophagocytic lymphohistiocytosis(HLH).Methods A total of 89 patients with EBV-HLH diagnosed in Children's Hospital of Chongqing Medical University from June 2006 to Octo-ber 2015 were divided into involved CNS group and non-involved group according to whether there was CNS involve-ment. The clinical manifestations,laboratory examinations and outcomes of these two groups were analyzed. Results Among these 89 patients with EBV-HLH,39 patients developed CNS disease,19 cases of them had neuro-logical symptoms or signs,including convulsions,unconsciousness,facial palsy,dysarthria,dysphagia,irritability,neck stiffness,Babinski sign positive,opisthotonus;9 cases of them had abnormal cerebrospinal fluid(CSF),with elevated white blood cell count and protein level;26 patients had abnormal brain images,including deepen or widening cortical sulci,atrophy,hemorrhage,high T2 signal in magnetic resonance imaging(MRI).The 3-year survival rate in involved CNS group was lower than those of non-involved group(66.7% vs.86.0%),and there was statistical significance (χ2=4.267,P=0.039).The involved CNS group had higher ferritin(χ2=5.092,3.921;P=0.024,0.048)and lower platelets(Z= -2.643,P=0.008)than those of non-involved group,and there were statistical significances.COX mul-tivariate analysis showed that neurological symptom and abnormal CSF were independent prognostic factors(RR=3.134, 3.339,all P<0.05).Conclusion CNS involvement is frequent in EBV-HLH.The prognosis of children with involved CNS group is worse than those of non-involved group.Neurological symptoms and abnormal CSF are related to poor prognosis.

Expression of EVI1 gene and its clinical significance in pediatric acute myeloid leukemia / 临床儿科杂志

Objective To investigate the relationship between EVI1 gene expression and clinical features and prognosis of children with acute myeloid leukemia (AML). Methods EVI1 gene was detected in AML children, correlation of clinical and lab features, prognosis of AML children with EVI1 gene were analyzed. Results EVI1 expression is positive in 38 of 145 children with AML. There were no significant differences in age, gender, hemoglobin concentration, leukocytes and platelet count, subtype of morphology, ratio of chromosomal anomaly and complex karyotypes between EVI1 positive and EVI1 negative group (P>0.05); coexist genes were detected in 9 cases (23.68%) of EVI1 positive group. Rate of complete remission (CR) was 91.67% in 24 cases of EVI1 positive patients received chemotherapy. Relapse rate was 64.29% and 14.29% in EVI1 positive patients who received chemotherapy and allo-hematopoietic stem cell transplantation (allo-HSCT), retrospectively and significant differences were found (P<0.05). There was no significant difference in CR but significant difference was found in event free survival (P<0.05) for EVI1 positive and EVI1 negative patients who received chemotherapy. EVI1 gene kept negative when bone marrow relapse occurred in two patients with EVI1 positive at diagnosis. Conclusion EVI1 gene may play adverse role in pediatric AML; prognosis of EVI1 positive AML patients can be improved by allo-HSCT; follow-up of EVI1 transcript levels is insufficient to monitoring of minimal residual disease.

Clinical analysis of 144 cases of infant leukaemia / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the clinical features, laboratory findings and treatment of infant leukemia.</p><p><b>METHODS</b>A retrospective analysis of the clinical data was performed of the cases with the diagnosis of infant acute leukemia from August 1993 to October 2014 in our hospital.</p><p><b>RESULTS</b>A total of 144 cases of infant leukemia were diagnosed in the defined period, including 83 cases of acute lymphoblastic leukemia, 55 myeloid leukemia, 1 hybrid acute leukaemia and 5 with incompatible cytological and immunophenotyping findings. The patients at the age of 9 to 12 months accounted for the largest proportion (38.2%), and 87.5% of the patients had hepatosplenomegaly; Six patients below 6 months old had skin infiltration. In about 1/3 of the patients, the white blood cells count was no greater than 100 × 10⁹ /L. Ninety-five patients had chromosome examinations, which identified chromosome abnormalities in 67 patients, including 18 positive for t(4;11)or t(9;11)or t(11;19), and younger patients were more likely to have chromosome abnormalities. Thirty-seven patients underwent MLL gene detection and 11 of them had positive results; the positive patients had higher rate of chromosome 11 abnormalities than the negative patients. Most of the patients gave up treatments after diagnosis and only 6 patients older than 6 months completed regular chemotherapeutic treatments and were now in complete remission.</p><p><b>CONCLUSION</b>Infant leukemia is a rare type of leukemia with different clinical features from other types of leukemia. The patients often present with hepatosplenomegaly, high white blood cell counts, MLL gene fusion, and chromosome 11 abnormalities. The prognosis of infant leukemia is not favorable, and the current treatment still relies on chemotherapy.</p>

Clinical analysis of 43 childhood APL with APL2008 / 重庆医学

Objective To evaluate the treatment of current status and prognosis in childhood APL with APL2008 ,which was administrated since 2008 in our center .Methods A total of 43 children with newly diagnosed APL between 2008 to 2014 were studied retrospectively .Treatment options and current status were summarized from 28 patients who received APL2008 therapy . Results Studied 43 patients were at median age of 8 years and 4 months ,with 28 boys and 15 girls .The main clinical manifestations were infection ,anemia ,bleeding ,fever ,hepatomegaly ,splenomegaly and lymphadenopathy .The proportions of low ,intermediate and high risk groups were 27 .9% ,48 .8% and 23 .3% ,respectively .Eleven cases could be diagnosed as DIC .Bone marrow morphology showed abnormal elevation of promyelocyte .37 patients had distinctive immunophenotype such as frequent expression of CD33 , CD117 and MPO .PML/RARαfusion gene positive rate was 100% in 43 children and cytogenetic analysis were positive in 37 cases , of which specific genetic lesion in APL cells with t (15 ;17)(q22 ;q12) was found in 28 cases ,and karyotypes was found in 9 cases as infrequent chromosomal abnormalities .In 43 patients ,4 cases were early dead from intracranial hemorrhage at early stage ,and 11 cases were given up early .There were only 2 cases dead ,2 cases relapsed and 1 case lost among 28 APL children ,which enabled ef‐ficacy analysis possible .96 .4% of these 28 cases achieved HCR .The 2 year Kaplan Meier estimates of OS and EFS were 85 .9% ± 7 .6% and 80 .4% ± 8 .8% .But OS and EFS would be 94 .7% ± 5 .1% and 88 .9% ± 7 .4% if 3 patients who had non standard treat‐ment were excluded .Conclusion Childhood APL were characterized by anemia ,bleeding ,fever and infiltration .APL′s coincidence rate between PML/RARa fusion gene and morphology ,immunology and cytogenetics were 95 .3% ,90 .2% and 86 .5% ,respective‐ly .APL2008 significantly improved the prognosis of APL .

Analysis of clinical and laboratory features of 217 pediatric hemophagocytic lymphohistiocytosis / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the incidence, clinical symptoms, signs and laboratory features of childhood hemophagocytic lymphohistiocytosis (HLH) in China.</p><p><b>METHODS</b>A retrospective study was performed on 217 pediatric patients with HLH who were admitted to Children's Hospital of Chongqing Medical University from January 2006 to April 2013. All patients'medical records were reviewed and analyzed.</p><p><b>RESULTS</b>The Male to female ratio was 1.11:1. The median onset age was 3 years and 5 months old (range of 6 months old to 16 years and 9 months old), and the age of onset peaked between 1-5 years old (61.3%). The most common causes of HLH was infection, especially Epstein-Barr virus-associated HLH (71.0%). Other causes included malignant hemophagocytic syndrome (MAHS), macrophage activation syndrome (MAS) and so on. The outstanding clinical manifestations including persistent fever (100.0%), hepatomegaly (92.6%), splenomegaly (88.4%), and more than half of cases with central nervous system involvement and pulmonary manifestations. Laboratory data indicated that the most prominent abnormality was elevated ferritin (98.0%), and the others were hemophagocytosis in bone marrow (90.7%) and coagulation abnormalities (76.5%). Abnormal lymphocytes classification is very common in HLH.</p><p><b>CONCLUSION</b>HLH is a heterogeneous disease, with a variety of the etiology and clinical manifestations. HLH-2004 diagnostic protocol had theoretical basis and clinical operability. The hepatitis damages related indicators, lymphocytes classification, central nervous system involvement and pulmonary performance can be used as reference value for HLH diagnosis.</p>

Prevalence and molecular analysis of α-thalassemia in preschool children in Chongqing city / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the incidence and the gene mutation frequencies and patterns of α-thalassemia in preschool children in Chongqing city.</p><p><b>METHODS</b>Cluster random sampling was used. A total of 1057 preschool children in three areas of Chongqing were screened by using routine blood test and hemoglobin electrophoresis analysis. Molecular analysis carried out for all the samples.</p><p><b>RESULTS</b>Of the 1057 samples, 55 cases were diagnosed as being carriers of α-thalassemia, which included 80 allele genes. Therefore, the frequency of α-thalassemia carriers in Chongqing was 5.20%. Of the 55 α-thalassemia carriers, five different deletions of α-thalassemia were identified, the three most common deletion types and proportions were 54.55% for the -α(3.7) deletion, 18.18% for --(SEA) deletion, and 9.08% for the -α(4.2) deletion, respectively; eight types of nondeletion defects were determined, containing one case of Hb Quong Sze and seven novel mutations of a-globin gene. Furthermore, 24 cases of α-Triplication were detected with the α-Triplication carrier rate of 2.55%. In addition, in this study we also found two cases of abnormal hemoglobin disorders occurred on α-globin gene, Hb J-Wenchang-Wuming and Hb Arya. Hb Arya was characterized in the Chinese population for the first time confirmed by literature retrieval.</p><p><b>CONCLUSION</b>In this study, we have clarified the carrier frequency and molecular spectrum of α-thalassemia in Chongqing, and we first reported the carrier incidence of α-Triplication in Chongqing. The materials obtained from this study would be of valuable reference for genetic counseling and the examination instruction of children in this area.</p>

Clinical study on cytomegalovirus infection after hematopoietic stem cell transplantation in 26 patients with primary immunodeficiency diseases / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the risk factors, and control measures of cytomegalovirus (CMV) infection after hematopoietic stem cell transplantion (HSCT) in children with primary immunodeficiency diseases(PID).</p><p><b>METHODS</b>We retrospectively analyzed results of 26 patients with PID-Wiskott-Aldrich syndrome (WAS, n=20), severe combined immunodeficiency (SCID, n=1) , X-linked chronic granulomatous disease (XCGD, n=2) and X-linked hyper-immunoglobulin M (IgM) syndrome (XHIM, n=3)-who underwent HSCT from June 2007 to December 2012 in our center. Serologic studies (ELISA) and weekly CMV infection surveillance (quantitative PCR, qPCR) were routinely performed before and after HSCT. Ganciclovir or forcarnet was used for pre-emptive and curative therapy.</p><p><b>RESULTS</b>All 26 patients were male with the median age at HSCT of 27 months (range 7-77 months). At a median follow up of 24 months (range 5-66 months), the 5-year overall survival rate was (75.0 ± 9.0) %. CMV infection occurred in 42.3% (11 of 26) of the patients, two of them developed CMV interstitial pneumonia (CMVIP). Univariate analysis revealed that the incidence of pre-transplant CMV infection between with and without CMV activation groups after HSCT was significantly different (62.5% vs 10.0%, P=0.010). Additional variables not associated with CMV infection were stem-cell sources, donor type, HLA disparity and acute GVHD (all P values>0.05).</p><p><b>CONCLUSION</b>CMV infection was a major complication of HSCT. Sensitive monitoring, early diagnosis, timely treatment may improve the survival rate for these PID undergoing HSCT.</p>

Clinical teaching for non-special medical practitioner in the department of pediatric hematology / 中华医学教育探索杂志

The common problems for non-special pediatric medical practitioners in the depart-ment of hematology include short-time of rotation, weak foundation of pediatric hematology and low enthusiasm of learning. The entrance education was highlighted in order to make refreshers familiar-ize with the severity of illness and eliminate the medical error. Basic theoretical study was strength-ened aiming at improving clinical skill and enhancing the learning interesting. Method of doctor-patient communication was reformed to reduce medical disputes.

Clinical analysis of 51 children with acute lymphoblastic leukemia suffered infection in hospital during induction remission / 重庆医科大学学报

Objective:To explore the correlation factors of children with acute lymphocytic leukemia (ALL) suffered infection in hospital during induction remission. Methods:The clinical data of 51 children with ALL suffered infection in hospital during induction remission were analyzed. Results:All the 51 patients got infected, the infection in patients who suffered neutropenia were hard to control. The infections commonly occurred in respiratory and digestive system,skin or mucous. Conclusion:Positive results of etiology were uncommon,and mortality of children is less than that of adult.