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Objective:To investigate the efficacy and safety of targeted therapy with Crizotinib for children with ALK gene mutation positive inflammatory myofibroblastic tumor (IMT). Methods:A retrospective analysis was performed on 4 children with ALK gene mutation positive IMT admitted to Shanghai Children′s Hospital from January 2019 to June 2021.Among them, 3 cases were given the targeted drug Crizotinib[280 mg/(m 2· time), q12h] orally, and 1 case was observed after complete tumor resection to analyze the efficacy and adverse drug reactions. Results:All 4 cases were male, aged from 2 years and 3 months to 11 years and 3 months.The tumors originated from the abdominal cavity in 2 cases, the right orbit in 1 case, and the right lung in 1 case.Pathological immunohistochemistry and fluorescence in situ hybridization were both positive for ALK gene mutation, and complete remission was achieved after comprehensive treatment.Among them, 3 patients were treated with oral Crizotinib, and 2 patients were tried to stop taking the drug for 1 year, relapsed 1 month later, and still achieved complete remission after the second treatment.The 4 cases were followed up for 8-30 months, and all survived.All the cases showed no abnormalities in blood image, liver and kidney function, myocardial enzyme profile, cardiac function, hearing and vision, and 2 cases showed prolonged Q-T interval in the course of Crizotinib treatment, which could be recovered by temporary withdrawal of drug, and no abnormality in electrocardiogram was found in continued drug use. Conclusions:Crizotinib was used to treat ALK mutation positive IMT, shrink tumor and consolidate postoperative treatment, which is a good choice for IMT in children with difficult surgical resection and refractory recurrence.
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The epidemic of coronavirus disease 2019 (COVID-19) puts higher demands on critical care medicine. Lots of studies have been conducted to solve COVID-19-related problems. Therefore, we reviewed the annual progress for COVID-19-related issues including antivirals threapies, respiratory support and immunomodulatory therapies and other critical issues, including the effect of antibiotic on mitochondrial damage and its relationship with sepsis, the goal and direction of antimicrobial de-escalation, drug prophylaxis of constipation, bleeding in gastrointestinal disorders and management of critical illness in the informalization era and so on. We hope to provide reference for clinical and scientific research work of the intensivists.
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The study was to investigate whether the application of checklist during ward rounds could improve the prognosis of critical ill patients.The results suggested that the checklist used during ward rounds could not improve the inhospital mortality of critically ill patients, but it increased the proportion of deep vein thrombosis prophylaxis, and shortened prophylaxis treatment of gastric stress ulcer.
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Objective Pancreatic enzymes may spread into the injured intestine, bloodstream,and cause the cascade of inflammatory reactions. Our objective was to explore trypsin expression in serum and vital organs in septic rats. Methods Trypsin levels in serum, heart, lung and jejunum were tested and compared between Escherichia coli endotoxin injected rats(SS), SS treated with a protease inhibitor (ulinastatin) and control group(SHAM). The correlations between serum trypsin, intestinal proteins and inflammation indices were assessed.Two components of mucosal barrier, i.e. mucin-2 and E-cadherin,were measured to evaluate the intestinal mucosal barrier function. The levels of tumor necrosis factor alpha (TNFα), interleukin-6(IL-6) and neutrophil elastase(NE) were measured to determine the inflammation indices.Results Compared to SHAM group, trypsin levels in serum[(73.71±9.14) ng/ml vs. (12.12±2.36) ng/ml],heart[(51.60±15.06) ng/ml vs. (6.39±3.53) ng/ml],lung [(54.73±5.57) ng/ml vs. (5.24±3.08) ng/ml] and jejunum(1.19 ± 0.48 vs. 0.40 ± 0.12) were significantly higher in SS group (all P<0.05). The level of serum trypsin had negative correlation with mucin-2 and E-cadherin, and positive correlation with TNFα, IL-6 and NE (all P<0.05). In rats treated with ulinastatin, trypsin levels were significantly decreased compared with those in SS group including in serum [(65.79±4.88)ng/ml]], heart [(26.33±12.03)ng/ml], lung [(28.73±14.46) ng/ml] and jejunum (0.80±0.20) (all P<0.05).Serum TNFα[ (247.34±16.97)ng/L vs. (178.78±40.81)ng/L] revealed similar changes in ulinastatin and SS group, whereas mucin-2(0.58 ± 0.14 vs. 0.89 ± 0.17)and E-cadherin(0.11 ± 0.04 vs. 0.23 ± 0.06)were both significantly elevated after administration of ulinastatin (both P<0.05). Conclusion Serum and tissue trypsin is elevated in septic rats. Protease inhibitor ulinastatin protects intestinal function by reducing inflammatory reaction.
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Autophagy is a dynamic process that allows recycling of long-lived proteins and damaged organelles into biosynthetic materials for maintaining the normal cellular homeostasis. Recently, accumulating evidence has indicated that autophagy played important roles in the pathogenesis of neuronal diseases. In this article, the research progress of autophagy in the pathogenesis and regulation mechanism of common nervous system diseases were reviewed to deepen the understanding of autophagy, and arouse researchers' attention on dynamic regulation of autophagy and alleviating autophagic flow injury.
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Objective To analyze the clinical data of children with Langerhans cell histiocytosis (LCH),to discuss the therapeutic effect,and to analyze the factors related to prognosis.Methods A total of 45 children diagnosed as LCH were divided into group A (18 cases with bone lesion only),group B(6 cases with soft tissue lesion),and group C (21 cases with viscera lesion) according to Shanghai Children's Hospital-LCH-2007 scheme [SCH-LCH-2007 (modified DAL-HX83/90) scheme].(1) Initial treatment:group A was treated with Prednisone (Pred) + Vincristine (VCR) for 28 weeks,and group B was treated with Pred + VCR + Etoposide (VP16) + Mercaptopurine (6MP) for 43 weeks,and group C was treated with Pred + VCR + VP16 + Methotrexate (MTX) +6MP for 52 weeks.(2) Re-treatment scheme after relapse included:①upgrading treatment,group A to group B,group B to group C.②Individual treatment for group C included VP16 modification,and maintained Thymosin and/or Ciclosporin etc.Results The total survival rate was 93.3％ (42/45 cases) and recurrence rate was 26.7％ (12/45 cases).Children in group A and B were all effective,while 2 patients in group C died,and 1 case missed follow-up.Multi-factor analysis showed that the factors like age,sex,group,skeleton,soft tissue,erythra,lymph gland,lung,mouth,ears,hypophysis pituitary had no statistical significance,but liver,spleen and blood involvement had statistical significance in disease relapse:liver (P=0.007 1),spleen (P=0.016 9),and blood (P=0.011 1).Conclusion LCH can affect several organs of children and relapse,and modified DAL-HX83/90 scheme is very effective.The liver,spleen and hematopoiesis system involvement is correlates with the relapse.
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Objective To explore whether albumin corrected anion gap (ACAG) is associated with long-term mortality of sepsis patients.Methods Adult patients with a diagnosis of sepsis within the first 24 hours (from December 2013 to December 2014) admitted to the intensive care unit (ICU) were included via the Sepsis database of West China Hospital Sichuan University. To record their long-term survival, patients were followed up by telephone interview one year after enrollment. ACAG was calculated according to the anion gap (AG) level within the first 24 hours admitted to ICU, and patients were divided into normal ACAG group (ACAG 12-20 mmol/L) and high ACAG group (ACAG > 20 mmol/L), and clinical characteristics and 1-year mortality were compared between groups. Patients were also divided into survivors and non-survivors according to the 1-year survival outcome, and multivariate logistic regression analysis was conducted to find independent risk factors for long-term mortality of sepsis patients.Results A total of 296 sepsis patients were enrolled in the study, with 191 (64.5%) in the high ACAG group and 105 (35.5%) in the normal ACAG group. There were no significant differences in age, gender, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), sequential organ failure assessment (SOFA), Charlson cormobidity index (CCI) and other background variables between groups. Compared with the normal ACAG group, patients who suffered from multiple organ dysfunction syndrome (MODS) in the high ACAG group were more prone to develop renal and gastrointestinal injury (43.5% vs. 25.7%, 52.9% vs. 33.3%, respectively), had significantly higher serum creatinine [SCr (μmol/L): 89.0 (61.0, 148.0) vs. 67.1 (48.0, 86.0)], greater need for continuous renal replacement therapy (CRRT, 16.8% vs. 6.7%), and significantly shorter length of ICU stay and hospital stay [days: 11 (5, 22) vs. 16 (18, 31), 21 (14, 39) vs. 28 (20, 47)], with statistically significant differences (allP < 0.05). It was shown by Kaplan-Meier survival analysis that 1-year cumulative survival for the high ACAG group was significantly lower than that of the normal ACAG group (55.0% vs. 67.7%,P = 0.046). It was shown by multivariate logistic regression that ACAG [odds ratio (OR) = 1.201, 95% confidence interval (95%CI) = 1.115-1.293,P = 0.000], APACHE Ⅱ (OR = 1.053, 95%CI = 1.011-1.098, P = 0.014), the incidence of septic shock (OR = 2.203, 95%CI = 1.245-3.898,P = 0.007), fungus infection (OR = 3.107, 95%CI = 1.702-5.674,P = 0.000), acute renal failure (OR = 2.729, 95%CI = 1.134-6.567,P = 0.025) and complicated with malignancy (OR = 2.929, 95%CI = 1.395-6.148,P = 0.005) were independent risk factors contributing to increased 1-year mortality among sepsis patients.Conclusion ACAG was an independent risk factor for 1-year mortality of sepsis patients.
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Objective To evaluate the efficacy of different treatment regimens for children with acute promye-locytic leukemia (APL)with positive PML -RARa fusion gene.Methods Thirty -two newly diagnosed APL patients were included in this study,treated either with all -trans -retinoic acid (ATRA)and chemotherapy (CT)(group A) or with ATRA and arsenic trioxide (ATO)(group B).Clinical situation and clinical efficacy were analyzed in patients in different groups.They were also separated into low risk group,intermediate risk group and high risk group according to different risk criteria.Clinical characteristics,complete remission,long -time survival and urine arsenic concentra-tion were analyzed and compared.Results (1 )Fourteen of 1 5 patients (93.3%)in group A achieved hematological complete remission (HCR)with a median time of 38 days (28 -63 days).Sixteen of 1 7 patients (94.1 %)in group B achieved HCR with a median time of 29 days (1 0 -42 days),which was significantly shorter than group A,and there was a significant difference between 2 groups(t =3.53,P =0.002).(2)The 5 -year event -free survival (EFS)of group A and group B was (60.0 ±1 2.6)% and (81 .9 ±9.5)%,respectively;the 5 -year EFS of group B was almost 20% higher than group A;while there was no significant difference between the 2 groups(χ2 =1 .1 5,P =0.28).The 5 -year overall survival (OS)of group A and group B was (72.2 ±1 1 .9)% and (94.1 ±5.7)%,respectively,the 5 -year OS of group B was almost 20% higher than group A;while there was no significant difference between the 2 groups(χ2 =2.88,P =0.1 6).(3)The 5 -year EFS of low plus intermediate group and high risk group patients was (74.0 ±1 0.1 )% and (64.8 ±1 4.3)%,the 5 -year EFS of low plus intermediate group was almost 1 0% higher than high risk group,but there was no significant difference between the 2 groups(χ2 =0.1 4,P =0.71 ).The 5 -year OS of low plus intermediate group and high risk group patients was (84.7 ±8.1 )% and (71 .3 ±1 4.1 )%,the 5 -year OS of low plus intermediate group was almost 1 0% higher than high risk group,while there was no significant difference be-tween the 2 groups(χ2 =0.36,P =0.55).(4)ATO related side effects were mild,including abnormal liver tests and e-lectrocardiogram,but were invertible after supportive therapy.At the end of each chemotherapy course,the urine arsenic concentration remained low and no chronic arsenic toxicity or second malignancies were found during the follow -up period.Conclusions The ATRA plus ATO regimen is a promising and better treatment for childhood APL with positive PML -RARa fusion gene compared with conventional chemotherapy.It was necessary to take risk stratification in APL patients.
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Objective To evaluate the practicability of using flow cytometry analysis for diagnosis of non-hodgkin′s lymphoma ( NHL) among children with serous effusion.Methods Twelve children who were diagnosed with malignant lymphoma from February 2011 to November 2013 at Shanghai Children′s hos-pital were recruited in this study.Pleural effusion and ascites samples were collected from those children who showed serous effusion as initial symptoms and analyzed by using flow cytometry based immunophenotyping. The antibodies used for immunophenotyping included CD45, CD10, CD33, CD7, CD1a, MPO, cCD3, CD79a, CD22, CD19, CD20, CD5, CD3,κ,λ,αβ,γδ,CD56 and other common markers for T, B and NK cells.Anti-CD30 antibody was used when necessary.Results All of the twelve cases with serous effusion were diagnosed with aggressive NHL.Six out of the twelve children including five cases with ascites and one case with pleural effusion showed high expression of CD20 and were classified as NHL-B type by flow cytom-etry.Three children with pleural effusion and one child with both pleural effusion and ascites were typed as NHL-T as characterized by monoclonal expression of αβorγδ.The other two children with pleural effusion were diagnosed with anaplastic large cell lymphoma with positive expression of CD30 and morphological het-erogeneity.Conclusion Flow cytometry analysis based immunophenotyping could be used as an auxiliary method for rapid and accurate diagnosis of lymphoma in children with serous effusions.
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Objective To analyzed the expression and clinical characteristics of CD 20 marker in children with B-lineage acute lymphoblastic leukemia ( B-ALL) and evaluated its medical significance in assessing the prognosis of disease.Methods From November 2008 to July 2012,125 cases of children with B-lineage acute lymphoblastic leukemia were collected from Shanghai Children ′s Hospital,including 79 males and 46 females, aged between 2 months to 14 years old.Flow cytometry based immunophenotyping and Minimal Residual Disease ( MRD) screening were applied to these children when newly diagnosed ,and MRD monitoring was again carried out after 35 days of induction remission therapy to those bears the MRD markers.These 125 patients were divided into CD20-positive group and CD20-negative group, and the corresponding clinical characteristics ,stage of immunophenotype ,MRD,risk stratification,and overall survival rates were recorded and compared.Data were statistically analyzed by using SPSS 16.0 software including χ2 test,t-test,standard deviation test and survival test.Results A total of 125 children with ALL-B,the group of CD20-positive were 48 while CD20-negative groups were 77,with a median age of 6 years old,and the median follow-up time of 30 months.Multivariate Cox regression Analysis showed that there was no clear correlation between CD20 expression level with age ,sex,white blood cell count at diagnosis ,fusion-gene,the stage of immunophenotype as well as risk stratification.The MRD-positive incidence at 35 days in the CD20 positive group was 35.4%,much higher than that of the CD20-negative group (16.9%),which is statistical significance (χ2 =5.236,P<0.05),while the overall survival rate (OS) for the CD20 positive group is 75.0%,much lower than that of the CD20 negative group (84.4%,χ2 =4.160,P<0.05).Conclusions CD20 positive expression level in children with B-lineage acute lymphoblastic leukemia at diagnosis demonstrates negative correlation with the overall survival rate of the patient ,indicating its usefulness as an additional joint marker for the current regimens to incorporate CD 20-targeted monoclonal therapy.
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Objective To investigate CD38 expression characteristic and the relation of clinic prognosis in children with acute lymphoblastic leukemia,in order to improve individual treatment.Methods Seventy-nine patients with childhood acute lymphoblastic leukemia(B-lineage) were enrolled into this study.Four-color fluorochrome labeled monoclonal antibodies were applyed to analyze the cell immunophenotypes and minimal residual disease screening.When CD38 low-expression was considered to be the effective screening marker and be used to continue monitoring.All patients were divided into CD38 low-expression groups and CD38 high-expression groups,to compared the immunophenotyping characteristic,risk stratification and survive rate of the two groups.All datas were assessed by means of SPSS16.0 and a P value of 0.05or less was considered to indicate statistical significance.Results All of 79 newly diagnosed ALL-B,The group of CD38 low-expression were 50/79 (63.3％) while the other group were 29/79(36.7％).of all patients,11 chilldren showed only a screening indicator-CD38/CD10/CD34/CD19,while 46 belonged to more than one markers (Such as TdT/CD10/CD34/CD19,CD66c/CD10/CD34/CD19 and CD45/CD10/CD34/CD19) and 18 no markers.The stratification of CD38 low-expression and CD38 high-expression groups as follows:21/5 patients with low-risk,14/15 with medium risk and 15/9 with high-risk.In the CD38 low-expression group,Early Pre-B 33,Pre-B 12,Mature-B 5,while in the CD38 high-expression group,Early Pre-B 21,Pre-B 5,Mature-B 3.This study showed that the high-risk stratification in the CD38 high-expression group was obviously higher than the CD38 low-expression group(F=6.24,P=0.044),but the survival time was signicantly shorter than CD38 low-expression group (x2 ＝ 5.22,P =0.022) and the difference was statistically significant.Conclusion CD38 as a MRD monitoring indicator of most acute lymphoblastic leukemia when it low-expression,CD38 high-expression in newly diagnosis childhood acute lymphoblastic leukemia(B-lineage) may be an independent risk factor for predicting poor prognosis.
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Objective To evaluate the values of CD64 expression in diagnosis of infected patients referred to intensive care unit.Method Sixty febrile children referred to the hospital intensive care unit from 2009.11 to 2010.03 were enrolled for a retrospective study.Fever was defined as a body temperature reaching 38℃ or higher with specifically bacterial infection or highly suspected with bacterial infection or viral infection.There were 28 patients with bacterial infection and 32 with viral infection.The non-infectious diseases such as juvenile rheumatoid arthritis and Kawasaki disease were excluded.The controls were 50 healthy children asking for physical examination.On admission,CD64 were measured by using flow cytometry,and blood routine examination,ESR,PCT,blood cultures and sputum cultures were simultaneously detected in all febrile patients.Data were statistically analyzed by using SAS 16.0 software.Data are given as means±SE.Categorical variables were analyzed using X2 test and continuous variables were compared by applying paired 1-tailed t test,Significance level was set at less than 0.05.Results of them,57.1%bacterial infection patients and 71.9%viral infection patients contracted pneumonia.CD64 in bacterial infection patients、viral infection patients and the subjects of control group were(12.6±9.7),(5.4±2.42)and (2.9±0.77),respectively.The CD64 in the bacterial infection patients were significantly higher than those in the virus infection patients(F=11.002,P=0.004).Conclusions CD64 in infected children referred to a hospital intensive care unit can be clearly distinguished between bacterial infections and viral infections, providing an important guidance and a flexible strategy for clinical treatment and determine the timing of withdrawal.
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To investigate the characteristics of acute respiratory distress syndrome(ARDS)in the casualties of a great earthquake in Wenchuan China on May 12,2008.Records of the hospitalized patients in ICU injured in the earthquakes were examined retrospectively.Among the total of 153 critical patients injured in the earthquake,52(34.0%)had ARDS.Among these 52 patients with ARDS,24(46.2%)had multiple organ dysfunction syndrome(MODS).9(17.3%)patients with ARDS dead.Approximate 34.0% of the casualties of a great earthquake in ICU had ARDS,MODS is a common associated conditions in these patients,infection phy a great role in these patients.