ABSTRACT
Objective:To investigate the clinical characteristics, treatment process and prognosis of children with severe side effects after chimeric antigen receptor T cell immunotherapy(CAR-T), so as to provide evidence for timely intervention after CAR-T treatment.Methods:From June 1, 2015 to May 31, 2020, children with cytokine release syndrome(CRS)or immune cell related neurotoxicity syndrome(ICANS)who were treated with CAR-T therapy in our hospital and revealed severe effects transferred to PICU were included in the study, and their clinical course and multiple laboratory examination data were systematically analyzed.Results:Seventeen children showed CRS reaction and entered PICU after CAR-T therapy.The most common clinical symptoms were respiratory distress(13 cases) and circulatory disorder(10 cases), of which 7 cases were complicated with severe ICANS.Serum interferon -γ(IFN-γ)and interleukin-6(IL-6)levels significantly increased after CAR-T cell infusion, reaching the peak at (5.1±1.6)days.The serum levels of IFN-γ and IL-6 in children with severe CRS were significantly higher than those in children with mild CRS(all P<0.05). The level of serum IL-6 in children with high tumor load was significantly higher than that in children with low tumor load( P<0.05). The mortality rate of children with elevated level of serum TNF-α was higher(5/5 vs.3/11, P<0.05). Children with severe CRS were more likely to develop grade 4 ICANS(4/4 vs.0/3, P<0.05). The mortality rate of children with oxygenation index(P/F value)<200 mmHg(1 mmHg=0.133 kPa) was higher(5/5 vs.2/12, P<0.05). The vasoactive inotropic score[ M( Min, Max)] in the death group was significantly higher than that in survival group[29.5(14.0, 50.0) vs.1.5(0, 25.0), Z=8.000, P=0.027]. Conclusion:Serum IL-6 and IFN-γ are crucial causes of CRS.High tumor load is one of the factors causing high level of serum inflammatory factors.Respiration and circulation systems are the most frequently involved systems.Therefore, the evaluation indexes of these two systems can help us judge the prognosis of children.
ABSTRACT
Objective:To analyze the clinical characteristics and risk factors for mortality of severe pneumocystis carinii pneumonia(PCP)in pediatric liver transplant(LT)recipients.Methods:The data of severe PCP in LT recipients diagnosed at Shanghai Children′s Medical Center from November 2019 to February 2021 were collected.The clinical characteristics and risk factors for 28-day mortality were analyzed.Results:Fifteen patients were enrolled in the study.Thirteen cases survived and 2 cases were non-survived.There was no routine anti-pneumocystis prophylaxis after LT.The median age of onset of PCP was 12(7, 26)months.The median time after LT was 3.00(0.33, 4.00)months.The onset clustered in November-December and June-August.All patients were mechanically ventilated, and some patients were given prone ventilation(11 cases), neuromuscular blocking agents(13 cases)and high concentration oxygen(more than 60%, nine cases). Fourteen cases were complicated with other infections.Two cases were complicated with pneumothorax and subcutaneous/mediastinal emphysema.There were 2 cases with septic shock-like manifestation, 1 case of right heart insufficiency, 1 case of right heart failure(death), and 1 case of multiple organ failure(death). Compared with the survived group, the non-survived group had higher pediatric risk of mortality Ⅲ score[3.5(0.0, 6.0)vs.8.5(5.0, 12.0), Z=1.993, P=0.046] and lactate dehydrogenase level[1 731.5(1 012.0, 3 270.0)U/L vs.4 387.5(3 606.0, 5 169.0)U/L, Z=2.148, P=0.032]. Conclusion:PCP in pediatric LT is critical and complicated.Pediatric risk of mortality Ⅲ scores and lactate dehydrogenase increase in 28-day hospitalized deaths.
ABSTRACT
Objective:To analyze the clinical characteristics and risk factors for mortality of severe pneumocystis carinii pneumonia(PCP)in pediatric liver transplant(LT)recipients.Methods:The data of severe PCP in LT recipients diagnosed at Shanghai Children′s Medical Center from November 2019 to February 2021 were collected.The clinical characteristics and risk factors for 28-day mortality were analyzed.Results:Fifteen patients were enrolled in the study.Thirteen cases survived and 2 cases were non-survived.There was no routine anti-pneumocystis prophylaxis after LT.The median age of onset of PCP was 12(7, 26)months.The median time after LT was 3.00(0.33, 4.00)months.The onset clustered in November-December and June-August.All patients were mechanically ventilated, and some patients were given prone ventilation(11 cases), neuromuscular blocking agents(13 cases)and high concentration oxygen(more than 60%, nine cases). Fourteen cases were complicated with other infections.Two cases were complicated with pneumothorax and subcutaneous/mediastinal emphysema.There were 2 cases with septic shock-like manifestation, 1 case of right heart insufficiency, 1 case of right heart failure(death), and 1 case of multiple organ failure(death). Compared with the survived group, the non-survived group had higher pediatric risk of mortality Ⅲ score[3.5(0.0, 6.0)vs.8.5(5.0, 12.0), Z=1.993, P=0.046] and lactate dehydrogenase level[1 731.5(1 012.0, 3 270.0)U/L vs.4 387.5(3 606.0, 5 169.0)U/L, Z=2.148, P=0.032]. Conclusion:PCP in pediatric LT is critical and complicated.Pediatric risk of mortality Ⅲ scores and lactate dehydrogenase increase in 28-day hospitalized deaths.
ABSTRACT
Objective:To explore the implementation of individualized lung protection ventilation strategy in pediatric acute respiratory distress syndrome(pARDS)guided by transthoracic electrical impedance tomography(EIT)and critical care ultrasound(CCU).Methods:We retrospectively analyzed the therapeutic process of protective ventilation strategy in one case of severe pARDS.EIT and CCU were used to guide the implementation of lung protective ventilation strategy.Results:EIT was used to guide lung recruitment and optimal positive end-expiratory pressure titration.CCU was used to assess hemodynamics and lung status of ARDS patient, and guide the implementation of right ventricular protective ventilation and circulatory protective ventilation.Finally, the patient eventually survived.Conclusion:The idea of ARDS protective ventilation has changed from traditional lung protective ventilation to right heart protective ventilation and circulatory protective ventilation, and finally achieved the protection of pulmonary vascular endothelium.EIT and CCU enrich the understanding of the pathophysiology and protective ventilation strategy in pARDS.
ABSTRACT
Objective@#To explore the clinical characteristics prevalence of respiratory adenovirus infections in children, and to provide reference for diagnosis, monitoring and timely treatment.@*Methods@#A total of 775 clinical specimens were collected from Shanghai Children′s Medical Center during November 2016 to November 2017, and 84 cases of adenovirus infections were detected by FilmArray.@*Results@#Among 775 samples, 84 samples(10.8%) were adenovirus positive.The epidemic peak of adenovirus infection was winter, spring and summer, especially in winter(20.8%), and the highest detection rate was in January(32.2%). The age ranged from 6 months to 2 years(47.7%). The common clinical manifestations are fever(91.7%), cough(96.4%), wheezing(48.8%), and shortness of breath(14.2%). A total of 15 cases(17.9%) had underlying diseases, the most of them were congenital heart diseases(9 cases, 10.7%). A total of 53 cases(63.1%) were mixed infection, and 21 cases(25.0%) were complicated with human rhinovirus/enterovirus.There were 5 cases of upper respiratory tract infection, 3 cases of bronchitis and 76 cases of pneumonia, including 55 cases of mild pneumonia and 21 cases of severe pneumonia.The average length of hospital stay was 8.3 days.The length of hospital stay, cases of wheezing and severe cases in the mixed infection group were significantly higher than those in the single infection group(P<0.05). Hospitalization days, wheezing symptoms, extrapulmonary symptoms, basic diseases and mixed infections in severe group were significantly higher than those in mild group(P<0.05).@*Conclusion@#Adenovirus infection occurs in children aged 6 months to 2 years, with a high incidence in winter, spring and summer.The peak month is January.The main clinical manifestations are high fever, cough and wheezing.Children with underlying diseases, wheezing symptoms, extrapulmonary symptoms and mixed infections are more likely to develop severe diseases.FilmArray detection system can quickly and accurately detect pathogens, provide a good basis for early diagnosis, monitoring and treatment of clinicians.
ABSTRACT
Objective@#To investigate the safety, feasibility and operation key points of whole lung lavage in infants with pulmonary alveolar proteinosis.@*Methods@#The clinical manifestations, genetic screening, therapeutic interventions and outcome of an infant with pulmonary alveolar proteinosis complicated with respiratory failure who received whole lung lavage in November 2018 in Shanghai Children′s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine were reported. Websites including PubMed, Springer Link, China National Knowledge Infrastructure (CNKI), Weipu Database, and Wanfang Database were searched using the key words of "whole lung lavage" "pediatric" and "pulmonary alveolar proteinosis" for articles published from their establishments to April 2019. Relevant literature was reviewed.@*Results@#A 3-month-old boy had experienced cough, shortness of breath and cyanosis for 1 week prior to admission to pediatric intensive care unit. Physical examination showed hepatosplenomegaly. Complete blood cell count showed mild anemia (hemoglobin 96 g/L) and normal white blood cells. The patient had normal C-reactive protein and normal blood platelet. Biochemical panel showed hypoalbuminemia (31 g/L), mildly elevated glutamic oxaloacetic transaminase (115 U/L) and blood ammonia (165 μmol/L), extremely elevated lactate dehydrogenase (>6 600 U/L) and hyperferritinemia (>4 500 μg/L). Chest computed tomography (CT) revealed decreased transmittance of both lungs, patchy high density shadow and ground glass opacity. Genetic testing revealed a mutation of c.625+1G>A in SLC7A7. Schiff reaction (PAS staining) in bronchoalveolar lavage fluid was positive. The patient was diagnosed with severe pneumonia, respiratory failure, lysinuria urinary protein intolerance, and pulmonary alveolar proteinosis. The patient received sequential unilateral whole lung lavage in 2 days and was successfully weaned from ventilator. He was discharged home breathing room air. Eleven articles (11 in English and non in Chinese) were reviewed. Twenty-one patients were included. After whole lung lavage, 76% (16/21) of the patients had improvement in respiratory function.@*Conclusions@#Whole lung lavage can effectively improve respiratory failure caused by pulmonary alveolar proteinosis in infant patients. The procedure is feasible and safe.
ABSTRACT
Objective:To explore the application value of FilmArray detection in children with acute lower respiratory tract infection and conduct economics analysis.Methods:From December 1, 2016 to November 30, 2017, 1 380 patients were enrolled in our study.Some children(FilmArray group) were tested for respiratory pathogens with FilmArray, while others (control group) were tested by 7-box antigen test of respiratory virus, gold colloid test of influenza and mycoplasma antibody.Those with underlying diseases were excluded.A total of 160 cases in the FilmArray group and 160 cases in the control group were obtained with tendency score matching method.The physical examination of pathogens, clinical indicators, usage of anti-infective drugs and hospitalization related costs were compared.Results:The positive rate of FilmArray test was significantly higher than that in control group (86.88% vs. 45.91%). The most common pathogens detected by FilmArray were adenovirus(39 cases), rhinovirus(34 cases), and parainfluenza virus(30 cases). In the FilmArray group, nine cases were positive for botulinum pertussis, accounting for 5.6% of the total.The hospitalization time of FilmArray group was shorter than that in control group [(8.89±6.23 days vs.(11.51±14.43)days]. In FilmArray group, the antibiotics were used for a shorter time, and 18 children did not use antibiotics during hospitalization.Compared with the control group, the hospitalization cost had no significant difference in the FilmArray group, but the antibiotic cost was less, as well as hospitalization time was shorter.The average hospitalization cost saved by using the FilmArray test was nearly 2 000 yuan per person. Conclusion:The application of FilmArray detection in children with acute lower respiratory tract infection can quickly and accurately identify a various infections of virus, bacteria and atypical pathogen, which guides using anti-infective drugs more reasonably.The application of FilmArray detection shortens the average hospitalization days of children, increases the utilization efficiency of medical resources, and reduces the medical cost and indirect economic loss of children’s families, which has certain economics significance.
ABSTRACT
Objective:To explore the clinical characteristics of influenza A virus infection in children, and provide evidence for early identification of severe patients.Methods:A total of 114 patients with influenza like symptoms admitted to Shanghai Children′s Medical Center from October 2017 to May 2019 were enrolled in our study.All the patients were confirmed influenza A infection by Xpert-Xpress influenza/respiratory syncytial virus detection platform.The patients were divided into mild influenza A group (47 cases) and severe influenza A group (67 cases with pneumonia). The clinical data of these patients were analyzed and compared.Results:The male to female ratio of 114 cases was 1.28∶1.The age of included patients ranged from 1 month 12 days to 12 years old, and the median age was 3.00 (4.27) years old.The most common clinical manifestations were fever, cough and wheezing, accounting for 79.82%, 68.42%, and 43.00%, respectively.The rate of mixed infection was 24.56%, and adenovirus(5.26%), respiratory syncytial virus(4.39%) as well as mycoplasma(3.51%) accounted for the top three, and the rate of mixed bacterial infection was 12.28%.The median age of the patients in the severe influenza A group was 1.00 (3.58) years, and that in the mild influenza A group was 4.00 (5.00) years, with statistical difference ( Z=-3.81, P<0.001). The mixed infection rate was 38.80% (26/67) in severe influenza A group and 4.26% (2/47) in mild influenza A group, with statistical difference ( χ2= 17.8, P<0.001). The neutrophil/lymphocyte ratio in peripheral blood was 2.64 (3.37) in severe influenza A group and 1.17 (2.02) in mild influenza A group, with statistical difference ( χ2=-2.46, P=0.01). Conclusion:Children with smaller age, mixed infection and higher neutrophil/lymphocyte ratio are easy to develop into severe cases.The detection system of Xpert-Xpress influenza / respiratory syncytial virus is a simple, rapid and accurate method for influenza detection, which provides a good basis for diagnosis and treatment.
ABSTRACT
Objective:To analyze the clinical characteristics, diagnosis and treatment strategies of cryptococcus neoformans infection in children, and to explore the application value of PCR and high-throughput gene analysis in the diagnosis and treatment of cryptococcus neoformans infection.Methods:The clinical data of children with cryptococcus neoformans infection were retrospectively analyzed, who were hospitalized in Shanghai Children′s Medical Center from July 1998 to December 2018, including epidemiological characteristics (age, gender, underlying disease, and contact history, etc.), clinical manifestations, laboratory tests, imaging studies, pathogen detection methods, and treatment and prognosis.Results:A total of ten children were enrolled in the survey, including five males and five females, and the median age was 6.28(4.08, 12.02) years; four cases had a history of poultry/soil/corrosion exposure; seven cases were diagnosed as cryptococcus neoformans meningitis, three cases were diagnosed as disseminated cryptococcal disease; five cases had underlying disease, including two cases of which were found to have primary immunodeficiency through high-throughput genetic analysis; headache with fever was the most common clinical symptom of cryptococcus neoformans meningitis.All three cases of disseminated cryptococcosis had primary or secondary immunodeficiency.All children were treated with 5-fluorocytosine + amphotericin B/amphotericin B liposome in induction therapy, and fluconazole in consolidation therapy.Notably, two cases showed hypokalemia during induction therapy, and one case showed mild renal dysfunction during consolidation treatment; five cases were cured, three cases were abandoned, one case was relapsed, and one case died.Conclusion:Children with cryptococcosis neoformans infection who are considered to have normal immune function may have primary immunodeficiency caused by gene mutation.PCR can improve the detection rate of cryptococcus neoformans and shorten the detection time.A significant increase in eosinophils may indicate the spread of infection.Hydration and regular potassium supplementation may reduce the toxicity of amphotericin B. Control of intracranial hypertension is the key to improve the success rate of treatment.
ABSTRACT
Objective:To explore the clinical characteristics prevalence of respiratory adenovirus infections in children, and to provide reference for diagnosis, monitoring and timely treatment.Methods:A total of 775 clinical specimens were collected from Shanghai Children′s Medical Center during November 2016 to November 2017, and 84 cases of adenovirus infections were detected by FilmArray.Results:Among 775 samples, 84 samples(10.8%) were adenovirus positive.The epidemic peak of adenovirus infection was winter, spring and summer, especially in winter(20.8%), and the highest detection rate was in January(32.2%). The age ranged from 6 months to 2 years(47.7%). The common clinical manifestations are fever(91.7%), cough(96.4%), wheezing(48.8%), and shortness of breath(14.2%). A total of 15 cases(17.9%) had underlying diseases, the most of them were congenital heart diseases(9 cases, 10.7%). A total of 53 cases(63.1%) were mixed infection, and 21 cases(25.0%) were complicated with human rhinovirus/enterovirus.There were 5 cases of upper respiratory tract infection, 3 cases of bronchitis and 76 cases of pneumonia, including 55 cases of mild pneumonia and 21 cases of severe pneumonia.The average length of hospital stay was 8.3 days.The length of hospital stay, cases of wheezing and severe cases in the mixed infection group were significantly higher than those in the single infection group( P<0.05). Hospitalization days, wheezing symptoms, extrapulmonary symptoms, basic diseases and mixed infections in severe group were significantly higher than those in mild group( P<0.05). Conclusion:Adenovirus infection occurs in children aged 6 months to 2 years, with a high incidence in winter, spring and summer.The peak month is January.The main clinical manifestations are high fever, cough and wheezing.Children with underlying diseases, wheezing symptoms, extrapulmonary symptoms and mixed infections are more likely to develop severe diseases.FilmArray detection system can quickly and accurately detect pathogens, provide a good basis for early diagnosis, monitoring and treatment of clinicians.
ABSTRACT
Objective@#To investigate the interaction between the gut microbiota and the sepsis in children by comparing the difference of gut microbiota between septic children and healthy children.@*Methods@#Genome was extracted from excrements of 18 cases of sepsis and 6 cases of healthy children.After genomic extraction, the hypervariable region of 16S rDNA gene were amplified and a small fragment library was constructed, and high-throughput sequencing was carried out, then the data of the lower machine was effectively sequenced by biological information processing.We could seek for the species that had changed significantly due to sepsis by comparing the diversity and the differences in the composition of intestinal flora between the two groups.@*Results@#The gut microbiome of the sepsis group was distinct from that of the health group.The operational taxonomic units in the sepsis group were significantly reduced compared with healthy group(P=0.001). The gut microbiome of children with sepsis had significantly lower diversity and richness compared with healthy group(P<0.05). A total of 7 species were shown to be differentially abundant between septic patients and healthy controls.The genus Pseudomonadales, Carnobacteriaceae and Granulicatella_elegans were significantly more abundant in the sepsis group; meanwhile the genus Pasteurellaceae, Ruminococcus, Lactobacillus_rogosae and Anaerostipes_butyratucus were less abundant in the sepsis group.In addition, the Granulicatella_elegans was characteristically present in the intestine of children with sepsis(P<0.001).@*Conclusion@#The microbial diversity and structure of the gut microbiome in children with sepsis are significantly different from those of healthy children.Our data suggest biomarkers identified in this study might participate in the pathogenesis or development process of sepsis.
ABSTRACT
Objective To investigate the interaction between the gut microbiota and the sepsis in children by comparing the difference of gut microbiota between septic children and healthy children. Methods Genome was extracted from excrements of 18 cases of sepsis and 6 cases of healthy children. After genom-ic extraction,the hypervariable region of 16S rDNA gene were amplified and a small fragment library was constructed,and high-throughput sequencing was carried out,then the data of the lower machine was effec-tively sequenced by biological information processing. We could seek for the species that had changed signifi-cantly due to sepsis by comparing the diversity and the differences in the composition of intestinal flora between the two groups. Results The gut microbiome of the sepsis group was distinct from that of the health group. The operational taxonomic units in the sepsis group were significantly reduced compared with healthy group(P＝0. 001). The gut microbiome of children with sepsis had significantly lower diversity and richness compared with healthy group(P<0. 05). A total of 7 species were shown to be differentially abundant be-tween septic patients and healthy controls. The genus Pseudomonadales,Carnobacteriaceae and Granulicatella elegans were significantly more abundant in the sepsis group; meanwhile the genus Pasteurellaceae, Ruminococcus,Lactobacillus rogosae and Anaerostipes butyratucus were less abundant in the sepsis group. In addition,the Granulicatella elegans was characteristically present in the intestine of children with sepsis(P<0. 001). Conclusion The microbial diversity and structure of the gut microbiome in children with sepsis are significantly different from those of healthy children. Our data suggest biomarkers identified in this study might participate in the pathogenesis or development process of sepsis.
ABSTRACT
Objective To explore the characteristics and value for predicting prognosis of cytokines in septic children with or without neutropenia.Methods Totally 138 septic children were divided into the neutropenia and non-neutropenia groups according to absolute neutropenic count.Septic children were divided into the shock and non-shock groups according to circulation function and organ perfusion.The levels of C-reactive protein,procalcitonin,cytokines,PRISM-Ⅲ and clinical outcomes were analyzed between the relative groups.Results (1) Totally 138 septic children were recruited,64 with neutropenia and 74 without neutropenia.The level of PRISM-Ⅲ of the neutropenia group was significantly higher than that of the non-neutropenia group (P=0.048).Mortality showed no significant difference between the two groups,but hospital stay in the neutropenia group was longer than that in the non-neutropenia group.The levels of C-reactive protein,IL-6,and IL-10 ihe neutropenia group were significantly higher than those of the non-neutropenia group (P=0.001;P=0.001;P=0.032).The level of TNF-α in the neutropenia group was significantly lower than that of the non-neutropenia group (P=0.032).(2)Among the 64 septic children with neutropenia,23 were combined with shock.The PRISM-Ⅲ level of the shock group was significantly higher than that of the non-shock group (P=0.001).The mortality of the shock group (43.5％,10/23) was significantly higher than the non-shock group (2.4％,1/41) (P=0.001).C-reactive protein,procalcitonin,IL-6,IL-10 and TNF-α in the shock group elevated obviously than those in the non-shock group (P=0.001;P=0.001;P=0.001;P=0.005;P=0.019).The area under receiver operating characteristic curve was 0.8 for IL-6 (cut-offvalue 315.38 pg/mL),0.8 for IL-10 (cutoff value 45.18 pg/mL),and 0.85 for TNF-α (cut-off value 1.95 pg/mL).(3) Among the 74 septic children without neutropenia,19 were combined with shock The PRISM-Ⅲ level of the shock group was significantly higher than that of the non-shock group (P=0.022).There was no significant difference of mortality between the two groups (P=0.3).IL-10 level in the shock group elevated obviously than that in the non-shock group (P=0.015).(4) Among the 42 children with sepsis shock,23 were combined with neutropenia.The PRISM-Ⅲ level of the neutropenia group was significantly higher than that of the non-neutropenia group (P=0.005).There was no significant difference of mortality between the two groups (P=0.29).The levels of C-reactive protein,procalcitonin,IL-6 and IL-10 in the neutropenia group were significantly higher than those in the non-neutropenia group (P=0.001;P=0.001;P=0.001;P=0.035).There was no difference of TNF-α level between the two groups.(5) Among the 96 children without sepsis shock,41 were combined with neutropenia.No difference of PRISM-Ⅲ level was observed between the neutropenia and nonneutropenia groups.The mortality of the neutropenia group was significantly lower than that in the non-neutropenia group (2.4％ vs 20％,P=0.02).The levels of C-reactive protein and IL-6 in the neutropenia group were significantly higher than those in the non-neutropenia group (P=0.005;P=0.033).The TNF-α level was significantly lower than that in the non-neutropenia group (P=0.007).Conclusions Compared to children without neutropenia,septic children combined with neutropenia have longer hospital stay,and septic shock children combined with neutropenia have higher mortality,and levels of IL-6,IL-10 and TNF-α were also significantly increased.The levels of IL-6,IL-10 and TNF-α can help to predict prognosis of children with sepsis.
ABSTRACT
Objective@#To analyze the clinical characteristics of children′s trematodiasis in order to enhance the level of clinical diagnosis and treatment.@*Methods@#The medical history, clinical manifestations, results of laboratory examination, conditions of diagnosis and treatment of 15 confirmed different types of children with trematodiasis from 2002 to 2017 in Shanghai Children′s Medical Center were retrospectively analyzed.@*Results@#Seven cases had eaten raw or undercooked freshwater crab, and 2 cases often drank raw stream or caught crabs.Five cases had polyserositis such as pleural effusion, ascites and pericardial effusion in different degrees.The eosinophil counts of 11 cases(73.3%) and IgE of 10 cases(76.9%) increased.Fifteen cases, trematodiasis serum antibody tests were positive, and 1 case′s fecal clonorchiasis was positive.Fifteen cases were improved by praziquantel.@*Conclusion@#The clinical characteristics of childhood trematodiasis are complex and atypical.Trematodiasis should be understood more deeply for clinician to avoid misdiagnosis.Praziquantel is a safe and effective drug for trematodiasis.
ABSTRACT
Objective To investigate the efficacy and safety of leukoreduction therapy in severe per-tussis in infants. Methods Therapeutic processes of 3 cases of severe pertussis in PICU of Shanghai Children′s Medical Center were retrospectively studied from October 2017 to May 2018. We reviewed the related literatures and summarized the time and effectiveness of leukoreduction therapy in severe pertussis. Results All 3 cases had leukocytosis,respiratory faliure,pulmonary hypertension and right heart failure. One case had multiple organ failure before undergoing exchange transfusion therapy and eventually died. Two cases that had pulmonary hypertension during the period of WBC′s rising accepted leukopheresis therapy before multiple organ failure,and eventually survived. We reviewed the foreign literatures which was almost case reports,leukoreduction therapy might improve the prognosis of severe pertussis in infants,but the time of using it had no conclusion. Conclusion This is the first report of leukoreduction therapy for the severe per-tussis in infants in China. It provides a new method for the treatment of severe pertussis in infants. It is worth looking forward to use this method combined with continuous renal replacement therapy and extracorporeal membrane oxygenation technology. In the future,multicenter clinical research should be done to explore the effectiveness and safety of leukoreduction therapy in the severe pertussis in infants.
ABSTRACT
Objective To explore the clinical manifestation,laboratory findings,treatment and prog-nosis of immune dysregulation,polyendocrinopathy,enteropathy,X-linked ( IPEX) syndrome,and to improve pediatricians'knowledge of this disease. Methods Clinical data of two cases of IPEX were retrospectively analyzed,and related literatures were reviewed. Results One of the two male children showed severe and early-onset enteropathy,another showed insulin-dependent diabetes onset. Both of them complicated with sep-sis. DNA sequencing of whole-genome exon group showed a mutation in FOXP3 gene. Finally,one of the two IPEX children accepted allogeneic hematopoietic stem cell transplantation( HSCT) . Another one was waiting for the treatment of HSCT. Conclusion IPEX should be considered also in infants with typical symptoms including early-onset refractory diarrhea, multiple endocrine disease and severe recurring infections. Gene sequencing mayl help diagnose the disease. Early HSCT can improve the patients'outcomes.
ABSTRACT
Objective To discuss the therapeutic significance of granulocyte colony stimulating factor (G-CSF) in the treatment of invasive Candida infections in congenital immunodeficiency,especially in cases with low level of interleukin 17(IL-17). Methods Therapeutic processes of 2 children suffering from invasive Candida infections secondary to congenital immunodeficiency were retrospectively studied,further-more,the related literatures were also reviewed. Results Whole-exome sequencing revealed CARD9 muta-tion in the first patient, who suffered from Candida albicans meningoencephalitis, while the other patient revealed STAT1 mutation suffering from recurrent lung abscess caused by Candida albicans,and both of them showed low level of blood IL-17. Routine antifungal drugs were insufficiency,even treatment period had pro-longed for several months. But after the G-CSF adjuvant therapy,their symptoms,signs and images recov-ered. With 5 to 10 months follow-up,no recurrent infections were found. Conclusion Antifungal drugs com-bined with G-CSF can effectively improve the treatment effect in invasive fungal infections secondary to immunodeficiency. Further more,genetic screening especially whole-exome sequencing can be suggested to find unusual immunodeficiency,which helps more individualized treatment.
ABSTRACT
Objective To explore the expression and clinical value of long non-coding RNA ( lncRNA) in sepsis children. Methods The peripheral blood samples were analyzed from 15 sepsis children ( sepsis group) ,7 septic shock children( septic shock group) and 21 healthy children( healthy control group) . The real time-polymerase chain reaction was used to explore the expression of 9 kinds of lncRNA (AK092960,LOC100192426,VHDJH,AC006230. 3,AC019097. 7,RP4-652L8. 2,RP11-108A15. 2,NKILA and AK023660) which are closely related to the nuclear factor-κB pathway of the sepsis. And further analysis of lncRNA expression between sepsis,septic shock and health children were carried out. The specificity and sensitivity of the lncRNAs compared with C-reactive protein, procalcitonin and WBC for identification of patients with sepsis or septic shock were also evaluated. Results The expression of VHDJH,AC019097. 7, RP4-652L8. 2,RP11-108A15. 2, NKILA and AK02366 in the sepsis group were significantly higher than those in the healthy control group(P < 0.01). Among them,the expression of VHDJH,AC019097.7, RP4-652L8. 2,NKILA and AK023660 in the septic shock group were higher than those in the sepsis group (P<0. 01). Although the specificity and sensitivity of VHDJH, AC019097. 7, RP4-652L8. 2, NKILA and AK023660 were higher than C-reactive protein,procalcitonin and WBC for sepsis and septic shock,respectively, there was no significant difference statistically(P >0.05). Conclusion VHDJH,AC019097.7,RP4-652L8.2, RP11-108A15. 2,NKILA and AK023660 could be the potential diagnostic biomarkers of sepsis and might reflect its severity.
ABSTRACT
Objective To study the clinical significance of thromboelastography (TEG) for determining the presence of coagulation disorders in septic children.Methods A total of 100 patients suffering from sepsis or severe sepsis in pediatric intensive care unit (PICU) of Shanghai Children's Medical Center from February 2014 to January 2015 were recruited.TEG tests and conventional coagulation laboratory tests (CCTs) including platelet count,fibrinogen,prothrombin time (PT),activated partial thromboplastin time,D-dimers,and international normalized ratio (INR) were carried out in all patients at the primary diagnosis of sepsis.Another 25 healthy children taking physical examination were enrolled as control group.Rank Sum Test was used to detect the differences in coagulation markers and TEG between the groups and there was statistical significance when P ＜ 0.05.Receiver operating characteristic (ROC) curves were used to evaluate the roles of TEG and CCTs tests in this study.Results Of them,there were 56 patients with sepsis and 44 with severe sepsis.The male to female ratio was 63∶ 37,the median age was 11.5 (3.3-48) months,and 71％ patients suffered from underlying disease.According to TEG,72 patients had coagulation disorders,including 28 with hypercoagulation and 44 with hypocoagulation.CCTs tests showed 50 patients had coagulation disorders,including 29 with non-overt DIC and 21 with overt DIC.The rate of hypercoagulability was significantly higher in non-DIC group than in non-overt DIC group (46％vs.17.2％,P =0.016).The rate of hypocoagulability was significantly higher in overt DIC group than in non-overt DIC group (100％ vs.44.8％,P ＜ 0.01).Patients with hypercoagulation disorders had significantly shorter R (coagulation reaction time) and K (coagulation formation time) and greater α (angle α),MA (maximal amplitude) and CI (comprehensive coagulation index) compared with control group (P ＜ 0.01).According to CCTs results,patients with hypercoagulation had significantly prolonged PT compared with control group (P =0.002).Compared with sepsis group,severe sepsis group had significantly prolonged R and K and lower α,MA and CI (P ＜ 0.01).ROC analysis demonstrated that area under the curve (AUC) of TEG and CCTs variables for diagnosis of severe sepsis were significantly greater than 0.5.Both variables of α (P =0.000 2) and K (P =0.004 1) had significantly greater AUCs compared with Fib.Conclusions There were 72％ septic patients with coagulation disorders.The hypercoagulability occurred earlier in patients with sepsis and the hypocoagulability occurred later in patients with severe sepsis.The TEG may provide important information for clinicians to deal with coagulation disorders in septic children.
ABSTRACT
Objective To investigate the change of extracellular histone level as well as the mecha-nism of the cytotoxicity of extracellular histones on vascular endothelial cell in sepsis. Methods Septic chil-dren admitted to PICU in Shanghai Children′s Medical Center between January 2010 and December 2014 were included in the present study. According to the diagnostic criteria of sepsis,the patients were divided into the sepsis group(51 cases) and the severe sepsis group(79 cases),with healthy children as the control group (108 cases). Patients in the severe sepsis group were further divided into the survival group(45 cases) and the non-survival group ( 34 cases ) based on 28-day mortality. The plasma concentration of extracellular histones in these children was determined and its correlation with the severity of sepsis was analyzed. Human umbilical vein endothelial cells(HUVECs) were incubated with calf thymus histone(CTH) at various con-centrations(0,50,100,200 and 300μg/ml) or different time periods(200μg/ml,0,5,15,30,45 and 60 mi-nutes) . The treated cells were subject to flow cytometer to measure the cell survival rate and scanning/trans-mission electron microscopy to observe their morphological changes. Western blot was used to detect the ex-pression of IκB and phosphor-p38/p38 in nuclear factor ( NF )-κB and mitogen-activated protein kinase ( MAPK) signaling pathways,while ELISA was used to determine the levels of tumor necrosis factor-α and interleukin-6. Results The levels of circulating histones in the septic children(2. 29 ± 1. 00) and severe sep-tic children ( 19. 17 ± 10. 20 ) were significantly higher than that of healthy controls ( 0. 23 ± 0. 26 ) ( P <0. 001),and the histone levels in the severe septic children were even higher(P<0. 001). Among the chil-dren diagnosed as severe sepsis,the level of circulating histones in the non-survivors was significantly higher than that in the survivors(29. 47 ± 5. 99 vs. 10. 94 ± 2. 68,P<0. 001). The survival rate of HUVEC gradually decreased along with the increase of CTH concentration or the treatment period in vitro. Data from electron microscopy showed that CTH treatment could directly disrupt the plasma membrane of HUVEC. Histones could also activate NF-κB and MAPK pathways,leading to the release of large amount of tumor necrosis fac-tor-α and interleukin-6. Conclusion The levels of extracellular histones in the septic children are correlated with the severity of sepsis. CTH can induce HUVEC death in a dose-and time-dependent manner. Extracellu-lar histone-induced endothelial dysfunction may mediate the progression of sepsis and such cytotoxicity might be due to the destruction of endothelial cell membranes and activation of the NF-κB and MAPK signaling pathways.