[Advances in gene therapy for inborn errors of immunity]. / åŸºå› æ²»ç–—åœ¨å ç–«å‡ºç”Ÿé”™è¯¯ä¸­çš„ç ”ç©¶è¿›å±•.

Inborn errors of immunity (IEI) are a diverse group of disorders caused by defects in immune system structure or function, involving both innate and adaptive immunity. The 2022 update of the IEI classification includes 485 distinct disorders, categorized into ten major disease groups. With the rapid development of molecular biology, the specific pathogenesis of many IEI has been revealed, making gene therapy possible in preclinical and clinical research of this type of disease. This article reviews the advancements in gene therapy for IEI, aiming to increase awareness and understanding of these disorders.

LASSO-derived nomogram for early identification of pediatric monogenic lupus.

BACKGROUND: Monogenic lupus is defined as systemic lupus erythematosus (SLE)/SLE-like patients with either dominantly or recessively inherited pathogenic variants in a single gene with high penetrance. However, because the clinical phenotype of monogenic SLE is extensive and overlaps with that of classical SLE, it causes a delay in diagnosis and treatment. Currently, there is a lack of early identification models for clinical practitioners to provide early clues for recognition. Our goal was to create a clinical model for the early identification of pediatric monogenic lupus, thereby facilitating early and precise diagnosis and treatment for patients. METHODS: This retrospective cohort study consisted of 41 cases of monogenic lupus treated at the Department of Pediatrics at Peking Union Medical College Hospital from June 2012 to December 2022. The control group consisted of classical SLE patients recruited at a 1:2 ratio. Patients were randomly divided into a training group and a validation group at a 7:3 ratio. A logistic regression model was established based on the least absolute shrinkage and selection operator to generate the coefficient plot. The predictive ability of the model was evaluated using receiver operator characteristic curves and the area under the curve (AUC) index. RESULTS: A total of 41 cases of monogenic lupus patients and 82 cases of classical SLE patients were included. Among the monogenic lupus cases (with a male-to-female ratio of 1:1.05 and ages of onset ranging from birth to 15 years), a total of 18 gene mutations were identified. The variables included in the coefficient plot were age of onset, recurrent infections, intracranial calcifications, growth and developmental delay, abnormal muscle tone, lymphadenopathy/hepatosplenomegaly, and chilblain-like skin rash. Our model demonstrated satisfactory diagnostic performance through internal validation, with an AUC value of 0.97 (95% confidence interval = 0.92-0.97). CONCLUSIONS: We summarized and analyzed the clinical characteristics of pediatric monogenic lupus and developed a predictive model for early identification by clinicians. Clinicians should exercise high vigilance for monogenic lupus when the score exceeds - 9.032299.

[Effects of Long-term Fertilizations on the Organic Carbon Components of Soil Macroaggregates and the Yield of Wheat in Wheat Fields on the Loess Plateau].

Soil macro-aggregates are the main location for soil organic carbon （SOC） sequestration, which is of great significance to improve soil fertility. This study aimed to understand the mechanisms of the organic carbon （OC） sequestration in macroaggregates and improve crop yield in wheat fields on the loess plateau. With the aggregate-density fractionation method, an eight-year experiment was conducted to investigate the following three factors： ① the effects of long-term fertilization on OC fractions within macroaggregates； ② the variation characteristics of OC fractions within macroaggregates, including coarse particulate organic carbon （cPOC）, fine particulate organic carbon （fPOC）, intra-microaggregate particulate organic carbon （iPOC）, free silt and clay particulate carbon （s+c_f）, and intra-microaggregate silt and clay particulate carbon （s+c_m）； ③ and the relationships between them and SOC input and yield formation. The treatments included no fertilization （CK）, farmer pattern （NP）, optimized fertilizers pattern （NPK）, optimized fertilizers + organic fertilizers pattern （NPKM）, and optimized fertilizers + biological organic fertilizers pattern （NPKB）. The results showed that the application of organic and chemical fertilizer （NPKM and NPKB） improved significantly the SOC content in macroaggregates compared with that in the single fertilizer treatment （NP and NPK）, which had a greater increase in SOC content in macroaggregates than that of the soil. All fertilization treatments had a tendency to increase the content of fractions iPOC, fPOC, and iPOC in macroaggregates, but silt and clay carbon （s+c_f and s+c_m） contents were decreased. The application of manure combined with chemicals markedly increased the allocations of fractions cPOC, fPOC, and iPOC reserves, but it greatly decreased （s+c_f） reserves allocation. However, the application of chemical fertilizers only significantly increased the proportion of cPOC reserves in macroaggregates. Correlation analysis showed that there were significant positive correlations among wheat grain yield and OC fractions （cPOC and fPOC） contents, SOC content, the OC content of >0.25 mm macroaggregates, and SOC input, and the correlation coefficient was 0.645-0.883. In conclusion, long-term fertilization, especially combined with organic fertilizer, could promote the free silt and clay carbon fraction （s+c_f） to transfer into other forms of OC components through the increase in soil carbon input in the wheat field of the loess plateau. Furthermore, the OC content of macroaggregates was increased overall, providing a good soil environment for crop yield.

Type I interferon pathway in pediatric systemic lupus erythematosus.

BACKGROUND: The role of type I interferon (IFN-I) signaling in systemic lupus erythematosus (SLE) has been well established. However, unanswered questions remain regarding the applicability of these findings to pediatric-onset SLE. The aim of this review is to provide an overview of the novel discoveries on IFN-I signaling in pediatric-onset SLE. DATA SOURCES: A literature search was conducted in the PubMed database using the following keywords: "pediatric systemic lupus erythematosus" and "type I interferon". RESULTS: IFN-I signaling is increased in pediatric SLE, largely due to the presence of plasmacytoid dendritic cells and pathways such as cyclic GMP-AMP synthase-stimulator of interferon genes-TANK-binding kinase 1 and Toll-like receptor (TLR)4/TLR9. Neutrophil extracellular traps and oxidative DNA damage further stimulate IFN-I production. Genetic variants in IFN-I-related genes, such as IFN-regulatory factor 5 and tyrosine kinase 2, are linked to SLE susceptibility in pediatric patients. In addition, type I interferonopathies, characterized by sustained IFN-I activation, can mimic SLE symptoms and are thus important to distinguish. Studies on interferonopathies also contribute to exploring the pathogenesis of SLE. Measuring IFN-I activation is crucial for SLE diagnosis and stratification. Both IFN-stimulated gene expression and serum IFN-α2 levels are common indicators. Flow cytometry markers such as CD169 and galectin-9 are promising alternatives. Anti-IFN therapies, such as sifalimumab and anifrolumab, show promise in adult patients with SLE, but their efficacy in pediatric patients requires further investigation. Janus kinase inhibitors are another treatment option for severe pediatric SLE patients. CONCLUSIONS: This review presents an overview of the IFN-I pathway in pediatric SLE. Understanding the intricate relationship between IFN-I and pediatric SLE may help to identify potential diagnostic markers and targeted therapies, paving the way for improved patient care and outcomes.

Application of cementoplasty in patients with symptomatic benign osteopathy disease.

BACKGROUND: The optimal treatment for some symptomatic, benign osteopathy lesions is yet to be identified. PURPOSE: To investigate the clinical efficiency of cementoplasty in managing symptomatic, benign osteopathy. MATERIAL AND METHODS: Between June 2006 and January 2020, we retrospectively enrolled 31 patients (10 men, 21 women; mean age = 46.5 ± 16.6 years; age range = 20-85 years), accounting for 34 treatment sites, who underwent percutaneous osteoplasty (14 treatment sites) and percutaneous vertebroplasty (20 treatment sites) with digital subtraction angiography (DSA) or DSA combined with computed tomography (CT). All the participants experienced different degrees of clinical symptoms with benign osteopathy lesions. The technical success of the procedure and occurrence of complications were recorded. Follow-up examinations were conducted to assess the treatment outcome using the MacNab criteria. RESULTS: All the participants had a diagnosis of benign osteopathy lesions before or after the cementoplasty. Surgery was successfully completed in all patients. Cement distributions were diffuse and homogeneous, with the complication of cement leakage occurring in 17.6% (6 of 34) of the lesions. The leakage occurred in the intervertebral disc (n = 1), the intra-articular space (n = 1), and the surrounding soft tissue (n = 4). Analysis of the treatment outcome using the MacNab criteria revealed that all patients showed improvement in their clinical symptoms to some extent and in the quality of life. CONCLUSION: Cementoplasty is an effective treatment for symptomatic, benign osteopathy, with the advantage of favorable clinical outcomes, and low complication rate.

A Cohort Study on Deficiency of ADA2 from China.

PURPOSE: Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. METHODS: A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. RESULTS: Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. CONCLUSION: To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.

Unique mutation spectrum of progressive pseudorheumatoid dysplasia in the Chinese population: a retrospective genotype-phenotype analysis of 105 patients.

BACKGROUND: Progressive pseudorheumatoid dysplasia (PPRD) is a rare genetic disease with autosomal recessive inheritance. There was a lack of genotype-phenotype correlation data from the Chinese population. This study aimed to identify the genotype and phenotype characteristics of Chinese PPRD patients and to conduct a genotype-phenotype analysis of Chinese PPRD patients. METHODS: Genetic analysis was performed for suspected PPRD patients from Peking Union Medical College Hospital. Medical records were collected from the electronic medical record system and patient-held portable health records. Published Chinese PPRD cases were gathered from both international and Chinese local databases. We collected demographic information, genetic variants, clinical manifestations, and imaging characteristics for further analysis. RESULTS: We included 105 Chinese PPRD patients in the current study. Thirty-three variants, including nine novels and five hotspot variants, were identified, with 26/33 (79%) variants exclusively seen in the Chinese population. Chinese PPRD patients share a phenotype similar to that in international reports. Joint involvement may progress with age (R2 = 0.2541). Long bone shortening and severe deformities occur in three patients with biallelic null variants, of which at least one variant is located in exon 2. Among hotspot variants, c.624dupA (p.C209Mfs*21) were associated with later onset and more involved joints. Elbow joints were more likely to be affected in patients carrying c.624dupA (p.C209Mfs*21) and c.866dupA (p.S209Efs*13). Shoulder joints are more likely to be involved in patients with biallelic null variants (P = 0.027). CONCLUSIONS: Chinese PPRD patients share a unique mutation spectrum. Among the five hotspot variants, c.624dupA is associated with later onset of disease, more extensive joint involvement, and a tendency to affect elbow joints. Biallelic null variants with at least one variant in exon 2 could be a likely cause of long bone shortening and severe deformities.

Efficacy and Safety of the Safe Triangular Working Zone Approach in Percutaneous Vertebroplasty for Spinal Metastasis.

OBJECTIVE: This study aimed to assess the technical feasibility, efficacy, and safety of the safe triangular working zone (STWZ) approach applied in percutaneous vertebroplasty (PV) for spinal metastases involving the posterior part of the vertebral body. MATERIALS AND METHODS: We prospectively enrolled 87 patients who underwent PV for spinal metastasis involving the posterior part of the vertebral body, with or without the STWZ approach, from January 2019 to April 2022. Forty-nine patients (27 females and 22 males; mean age ± standard deviation [SD], 57.2 ± 11.6 years; age range, 31-76 years) were included in group A (with STWZ approach), accounting for 54 vertebrae. Thirty-eight patients (18 females and 20 males; 59.1 ± 10.9 years; 29-81 years) were included in group B (without STWZ approach), accounting for 57 vertebrae. Patient demographics, procedure-related variables, and pain relief as assessed using the visual analog scale (VAS) were collected at different time points. Tumor recurrence in the vertebrae after PV was analyzed using Kaplan-Meier curves. RESULTS: The STWZ approach was successful from T1 to L5 without severe complications. Cement filling was satisfactory in 47/54 (87.0%) and 25/57 (43.9%) vertebrae in groups A and B, respectively (p < 0.001). Cement leakage was not significantly different between groups A and B (p = 1.000). Mean VAS score ± SD before and 1 week and 1, 3, 6, 9, and 12 months after PV were 7.6 ± 1.8, 4.2 ± 2.0, 2.7 ± 1.9, 1.9 ± 1.5, 1.7 ± 1.4, 1.7 ± 1.1, and 1.6 ± 1.3, respectively, in group A and 7.2 ± 1.7, 4.0 ± 1.3, 3.4 ± 1.6, 2.4 ± 1.2, 1.8 ± 1.0, 1.4 ± 0.5, and 1.7 ± 0.9, respectively, in group B. Kaplan-Meier analysis showed a lower tumor recurrence rate in group A than in group B (p = 0.001). CONCLUSION: The STWZ approach may represent a new, safe, alternative/auxiliary approach to target the posterior part of the vertebral body in the PV for spinal metastases.

Analysis of clinical characteristics of children with Aicardi-Goutieres syndrome in China.

BACKGROUND: Aicardi-Goutieres syndrome (AGS) is an inflammatory disorder belonging to the type I interferonopathy group. The clinical diagnosis of AGS is difficult, which can lead to a high mortality rate. Overall, there is a lack of large-sample research data on AGS in China. We aim to summarize the clinical characteristics of Chinese patients with AGS and provide clues for clinical diagnostic. METHODS: The genetic and clinical features of Chinese patients with AGS were collected. Real-time polymerase chain reaction was used to detect expression of interferon-stimulated genes (ISGs). RESULTS: A total of 23 cases were included, consisting of 7 cases of AGS1 with three prime repair exonuclease 1 mutations, 3 of AGS2 with ribonuclease H2 subunit B (RNASEH2B) mutations, 3 of ASG3 with RNASEH2C, 1 of AGS4 with RNASEH2A mutations, 2 of AGS6 with adenosine deaminase acting on RNA 1 mutations, and 7 of AGS7 with interferon induced with helicase C domain 1 mutations. Onset before the age of 3 years occurred in 82.6%. Neurologic involvement was most common (100%), including signs of intracranial calcification which mainly distributed in the bilateral basal ganglia, leukodystrophy, dystonia, epilepsy, brain atrophy and dysphagia. Intellectual disability, language disability and motor skill impairment were also observed. Skin manifestations (60.87%) were dominated by a chilblain-like rash. Features such as microcephaly (47.62%), short stature (52.38%), liver dysfunction (42.11%), thyroid dysfunction (46.15%), positive autoimmune antibodies (66.67%), and elevated erythrocyte sedimentation rate (53.85%) were also found. The phenotypes of 2 cases fulfilled the diagnostic criteria for systemic lupus erythaematosus (SLE). One death was recorded. ISGs expression were elevated. CONCLUSIONS: AGS is a systemic disease that causes sequelae and mortality. A diagnosis of AGS should be considered for patients who have an early onset of chilblain-like rash, intracranial calcification, leukodystrophy, dystonia, developmental delay, positive autoimmune antibodies, and elevated ISGs, and for those diagnosed with SLE with atypical presentation who are nonresponsive to conventional treatments. Comprehensive assessment of vital organ function and symptomatic treatment are important.

Thalidomide may be an effective drug for Blau syndrome: a case report.

Blau syndrome (BS) is a monogenic autoinflammatory disease caused by mutations in nucleotide-binding oligomerization domain containing 2 (NOD2). BS is characterized by the clinical triad of granulomatous dermatitis, arthritis and recurrent uveitis. Due to the low incidence of BS and the lack of treatment studies with large samples, a specific treatment scheme has not been established. We report the case of a patient with BS that was uncontrollable with various immunosuppressive therapies but had a good response to thalidomide. She had the typical triad of rash, arthritis and uveitis. Gene sequencing indicated a NOD2 heterozygous missense variant (c.1759C > T, p.R587C), which has been reported as a pathogenic mutation. The BS diagnosis was confirmed. After treatment with methotrexate, an anti-tumour necrosis factor (TNF)-α inhibitor and corticosteroids, the patient's clinical symptoms and inflammatory indicators remained uncontrolled, and she experienced multiple side effects, such as hypertension and growth retardation attributed to prolonged corticosteroid use. After treatment with thalidomide, her condition was controlled without recurrence or side effects, and corticosteroids were stopped as soon as possible. This report suggests that thalidomide may be effective for BS treatment, but more research is needed to evaluate its long-term efficacy and side effects.

Toward a better understanding of type I interferonopathies: a brief summary, update and beyond.

BACKGROUNDS: Type I interferonopathy is a group of autoinflammatory disorders associated with prominent enhanced type I interferon signaling. The mechanisms are complex, and the clinical phenotypes are diverse. This review briefly summarized the recent progresses of type I interferonopathy focusing on the clinical and molecular features, pathogeneses, diagnoses and potential therapies. DATA SOURCES: Original research articles and literature reviews published in PubMed-indexed journals. RESULTS: Type I interferonopathies include Aicardi-Goutières syndrome, spondyloenchondro-dysplasia with immune dysregulation, stimulator of interferon genes-associated vasculopathy with onset in infancy, X-linked reticulate pigmentary disorder, ubiquitin-specific peptidase 18 deficiency, chronic atypical neutrophilic dermatitis with lipodystrophy, and Singleton-Merten syndrome originally. Other disorders including interferon-stimulated gene 15 deficiency and DNAse II deficiency are believed to be interferonopathies as well. Intracranial calcification, skin vasculopathy, interstitial lung disease, failure to thrive, skeletal development problems and autoimmune features are common. Abnormal responses to nucleic acid stimuli and defective regulation of protein degradation are main mechanisms in disease pathogenesis. First generation Janus kinase inhibitors including baricitinib, tofacitinib and ruxolitinib are useful for disease control. Reverse transcriptase inhibitors seem to be another option for Aicardi-Goutières syndrome. CONCLUSIONS: Tremendous progress has been made for the discovery of type I interferonopathies and responsible genes. Janus kinase inhibitors and other agents have potential therapeutic roles. Future basic, translational and clinical studies towards disease monitoring and powerful therapies are warranted.

The clinical phenotype and genotype of NLRP12-autoinflammatory disease: a Chinese case series with literature review.

BACKGROUND: The nucleotide-binding oligomerization domain-like receptor protein 12 (NLRP12)-autoinflammatory disorder (NLRP12-AD) is a rare autoinflammatory disease characterized by recurrent fever, rash as well as musculoskeletal symptoms, which is rarely reported in Asian populations. METHODS: Three cases of NLRP12-AD presented to our hospital were studied after parental consents were obtained. Clinical presentations were recorded on a standardized case report form. Mutations of NLRP12 were detected by primary immunodeficiency disease panels and further examined by Sanger sequencing. PubMed literature search for relevant studies of systemic autoinflammatory disorders, especially NLRP12-AD between January, 2000 and January, 2019 was carried and the clinical data were summarized. Comparisons were made between groups in terms of onset age and of ethnicity. RESULTS: All our patients presented with fever, rash and arthritis/arthralgia, and sensorineural as well as sensorineural deafness (1/3), uveitis (1/3), abdominal pain (1/3), and myalgia (1/3). Two novel mutation variations, p.W581X and p.L558R, are reported here. In addition, we also found that two patients inherited the mutated alleles from their healthy parents, and this may be evidence of haploinsufficiency. CONCLUSIONS: Although the genotypes are similar, the clinical manifestations between Chinese patients and Western patients vary thus highlighting the possible influence of ethnic and environmental factors. On the other hand, some genetic mutations may lead to specific phenotype, as we have found a high prevalence of sensorineural hearing loss among p.R284X patients.

Characterization of microbiota in systemic-onset juvenile idiopathic arthritis with different disease severities.

BACKGROUND: Systemic-onset juvenile idiopathic arthritis (SoJIA) is one of most serious subtypes of juvenile idiopathic arthritis. Although the pathogenesis of SoJIA remains unclear, several studies have suggested a correlation between gut dysbiosis and JIA. Further understanding of the intestinal microbiome may help to establish alternative ways to treat, or even prevent, the disease. AIM: To explore alterations in fecal microbiota profiles in SoJIA patients and to evaluate the correlations between microbiota and clinical parameters. METHODS: We conducted an observational single-center study at the Pediatric Department of Peking Union Medical College Hospital. Children who were diagnosed with SoJIA at our institution and followed for a minimum period of six months after diagnosis were recruited for the study. Healthy children were recruited as a control group (HS group) during the same period. Clinical data and stool samples were collected from SoJIA patients when they visited the hospital. RESULTS: The SoJIA group included 17 active and 15 inactive consecutively recruited children; the control group consisted of 32 children. Firmicutes and Bacteroidetes were the two most abundant phyla among the total sample of SoJIA children and controls. There was a significant difference among the three groups in observed species, which was the highest in the Active-SoJIA group, followed by the Inactive-SoJIA group and then HS group (Active-SoJIA vs HS: P = 0.000; and Inactive-SoJIA vs HS: P = 0.005). We observed a lower Firmicutes/Bacteroidetes ratio in SoJIA patients (3.28 ± 4.47 in Active-SoJIA, 5.36 ± 8.39 in Inactive-SoJIA, and 5.67 ± 3.92 in HS). We also observed decreased abundances of Ruminococcaceae (14.9% in Active-SoJIA, 17.3% in Inactive-SoJIA, and 22.8% in HS; Active-SoJIA vs HS: P = 0.005) and Faecalibacterium (5.1% in Active-SoJIA, 9.9% in Inactive-SoJIA, and 13.0% in HS; Active-SoJIA vs HS: P = 0.000) in SoJIA compared with HS. By contrast, the abundance of Bacteroidaceae was the highest in the Active-SoJIA group, followed by the Inactive-SoJIA and HS groups (16.5% in Active-SoJIA, 12.8% in Inactive-SoJIA, and 9.7% in HS; Active-SoJIA vs HS: P = 0.03). The Spearman correlation analysis revealed a negative correlation between Proteobacteria or Enterobacteriaceae and juvenile arthritis disease activity score on 27 joints (JADAS-27). CONCLUSION: The composition of the intestinal microbiota is different in SoJIA patients compared with healthy children. The dysbiosis presents partial restoration in inactive status patients.

[Clinical features and TTC21B genotype of a child with nephronophthisis type 12].

Nephronophthisis (NPHP) is a group of autosomal recessive tubulointerstitial cystic kidney disorders. This article reports a case of NPHP type 12 caused by TTC21B mutations. The girl had an insidious onset, with moderate proteinuria, renal dysfunction, stage 2 hypertension, situs inversus, and short phalanges when she visited the hospital for the first time at the age of 3 years and 6 months. The renal lesions progressed to end-stage renal disease (ESRD) before she was 4 years old. Urine protein electrophoresis showed glomerular proteinuria. There were significant increases in urinary ß2-microglobulin and α1-microglobulin. Gene detection revealed two compound heterozygous mutations, c.1552T>C (p.C518R) and c.752T>G (p.M251R), in the TTC21B gene, which came from her father and mother respectively. The c.752T>G mutation was a novel mutation. It is concluded that besides typical tubular changes of NPHP, marked glomerular damage is also observed in patients with TTC21B gene mutations.

Clinical features and prognosis of patients with thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus: a review of 25 cases.

OBJECTIVE: To report the clinical features of patients with systemic lupus erythematosus (SLE) associated with thrombotic thrombocytopenic purpura (TTP). Their diagnosis, treatment, and prognosis were also discussed. METHODS: A total of 25 TTP-SLE pediatric patients were included in this study. Their clinical symptoms, laboratory findings, disease activity, and renal biopsy were retrospectively reviewed. RESULTS: The median age of the patient cohort was 14 years old. Nine patients were first diagnosed with SLE, followed by the diagnosis of TTP-SLE, whereas 15 patients were diagnosed with TTP and SLE concurrently. All the 25 TTP-SLE patients had decreased platelet count and microangiopathic hemolytic anemia. Fever, rash, edema and neurological symptoms were the main clinical symptoms. Fragmentation of erythrocytes on blood smear and increased LDH were found in all patients. Nineteen patients (76%) had impaired renal function. Renal biopsy showed that most of the patients had lupus nephritis class IV (20%) and TMA (20%). 13 patients (52%) were treated with glucocorticoids in combination with immunosuppressive agent, and 10 patients (40%) were treated with plasma exchange combined with glucocorticoids plus immunosuppressive agent. One patient died due to lung infection; others had disease remission. Fifteen patients had follow-up regularly, and their conditions were stable. CONCLUSION: Patients with TTP-SLE often had moderate to severe lupus disease activity. Testing of LDH level and blood smear should be performed when kidney and neurological symptoms arise in children with SLE. The use of combination therapy, glucocorticoids plus immunosuppressive agent, provided satisfactory clinical outcome. Patients with refractory TTP-SLE will also need plasma exchange therapy.

Cyclophosphamide for the treatment of acute lymphoblastic leukemia: A protocol for systematic review.

BACKGROUND: Previous clinical trials have reported that cyclophosphamide can be used for the treatment of acute lymphoblastic leukemia (ALL). However, its efficacy is still unclear. In this systematic review study, we aim to evaluate its efficacy and safety for ALL. METHODS: The following 9 databases will be searched from their inception to the present: Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), and four Chinese databases. The randomized controlled trials or case control studies of cyclophosphamide that assess the clinical efficacy and safety in patients with ALL are included. The methodological quality of all eligible included studies will be assessed by the Cochrane risk of bias tool.The primary outcome measurement will be all-cause mortality at the period of treatment and follow-up. The secondary outcome measurements will include the health-related quality of life (HRQL), postinduction complete remission (CR) rate, event-free survival (EFS), relapse rate, and adverse events. Two authors will independently select eligible studies, exact data, and assess the methodological quality of included studies. RevMan 5.3 software will be used to synthesize the data. Reporting bias will be evaluated by the funnel plots, Begg, and Egger tests. RESULTS: This systematic review will evaluate the clinical efficacy and safety of cyclophosphamide for ALL. DISSEMINATION AND ETHICS: The findings of this review will summarize the present evidence of cyclophosphamide for ALL, and may provide guidance for clinical practice of cyclophosphamide for ALL. Its results will be published through peer-reviewed journals. This study does not need ethic approval, because it will not involve the individual data. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018119333.

Percutaneous vertebroplasty in the treatment of malignant vertebral compression fractures with epidural involvement.

Purpose: To evaluate the safety and the clinical efficacy of percutaneous vertebroplasty (PVP) in treating malignant spinal tumors and malignant vertebral compression fractures with epidural involvement. Materials and methods: 43 patients with spinal metastatic tumors and malignant vertebral compression fractures with epidural involvement were treated using PVP. American Spinal Injury Association (ASIA) impairment scale results at presentation were used to divide patients into 2 groups. Patients in group A had no symptoms of neurological compression (n = 25); and patients in group B had symptoms of neurological compression (n = 28). A 13G bone puncture needle was placed across the pedicle of the fractured vertebra, and polymethyl methacrylate (PMMA) was injected into the fractured vertebral body under fluoroscopic control. Patients were seen in follow-up at 1, 3, and 6 months after the procedure and every six months thereafter. Results: PVP was technically successful and well-tolerated in all patients. Clinical assessment at the final follow-up found complete pain relief (n = 19) or good pain relief (n = 14) in 33 patients (62.3%, 95% CI: 49%, 76%). ASIA impairment scale assessment at the final follow-up demonstrated symptoms of neurologic compression in 31 patients and no symptoms of neurologic compression in 22 patients. Symptoms of neurologic compression were found in five group A patients and eight group B patients. Conclusions: PVP was a safe and moderately effective procedure in the treatment of malignant vertebral compression fractures with epidural involvement.