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BACKGROUND: The aim of this study was to analyze the clinical significance of cerebrospinal fluid (CSF) cytokines in hemophagocytic lymphohistiocytosis associated with central nervous system (CNS-HLH). METHODS: CSF cytokine levels, including interferon (IFN)-γ, soluble CD25 (sCD25), interleukin (IL)-6, IL-10, IL-18, and CXCL9 were measured at disease onset and during the treatment. Five newly diagnosed patients with demyelination disease were enrolled for comparison. RESULTS: Sixty-five samples from 36 patients (13 in the CNS group and 23 in the non-CNS group) were detected. Levels of CSF IFN-γ, sCD25, IL-10, IL-18, and CXCL9 in the CNS group were higher than those in the non-CNS group (P=0.038, <0.001, <0.001, 0.005, and <0.001), and levels of CSF sCD25, IL-10, IL-18, and CXCL9 in the CNS group were higher than those in the demyelination group (P=0.001, 0.008, 0.004, and 0.003). There was no significant difference in IL-6 levels among the 3 groups (P=0.339). CSF IFN-γ, sCD25, IL-10, IL-18, and CXCL9 could assist in diagnosing CNS-HLH. The diagnostic efficiency of CSF sCD25, IL-10, and CXCL9 was better, with a cutoff value of 154.64, 1.655, and 19.54 pg/mL, respectively. The area under the curve was >0.9, with sensitivity and specificity >80%. Correlation analysis suggested that in the CNS group, IFN-γ levels in CSF and serum correlated positively (R=0.459, P=0.007), while there was no correlation between CSF CXCL9 and serum IFN-γ (P=0.915). CONCLUSIONS: CSF IFN-γ, sCD25, IL-10, IL-18, and CXCL9 levels were significantly higher in HLH patients with CNS involvement than those without and could predict HLH patients with CNS involvement. CSF CXCL9 might be a more sensitive biomarker to CNS-HLH than IFN-γ, while CSF IL-6 does not seem to play a vital role.
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BACKGROUND: We aimed to analyze the clinical characteristics of peripheral Epstein-Barr virus (EBV)-infected lymphocyte subtypes in children with chronic active EBV infection (CAEBV). METHODS: The levels of peripheral EBV infection of CD4+ T cells, CD8+ T cells, and CD56+ natural killer (NK) cells were determined by flow cytometry and quantitative polymerase chain reaction (qPCR) in patients with CAEBV from July 2017 to July 2022. RESULTS: In total, 112 children with CAEBV were evaluated. Of these, CD4+ type, CD8+ type, and CD56+ type were defined in 44, 21, and 47 patients, respectively. Patients with CD8+ T-cell type had a significantly higher frequency of rash, while hepatomegaly was more common in patients with CD4+ T-cell type. Generally, patients with CD8+ T-cell type had the lowest overall survival rate (P = .017). Patients treated with chemotherapy and hematopoietic stem cell transplantation (HSCT) had a better prognosis (P = .001). In multivariate analysis, rash, hemophagocytic lymphohistiocytosis, CD8+ T-cell type, and no decrease of plasma EBV-DNA after treatment were independent indicators of poor prognosis (P = .002, .024, .022, and .012, respectively). CONCLUSIONS: In children with CAEBV, rash was more frequent in patients with CD8+ T-cell type, whereas patients with CD4+ T-cell type were more likely to develop hepatomegaly. Patients with CD8+ T-cell type had a poor prognosis despite receiving chemotherapy or further HSCT.
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Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Células Asesinas Naturales , Humanos , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Masculino , Femenino , Niño , Preescolar , Herpesvirus Humano 4/inmunología , Linfocitos T CD8-positivos/inmunología , Células Asesinas Naturales/inmunología , Linfocitos T CD4-Positivos/inmunología , Enfermedad Crónica , Adolescente , Subgrupos Linfocitarios/inmunología , Lactante , Pronóstico , Trasplante de Células Madre Hematopoyéticas , ADN Viral/sangre , Antígeno CD56RESUMEN
Cartilage, an important connective tissue, provides structural support to other body tissues, and serves as a cushion against impacts throughout the body. Found at the end of the bones, cartilage decreases friction and averts bone-on-bone contact during joint movement. Therefore, defects of cartilage can result from natural wear and tear, or from traumatic events, such as injuries or sudden changes in direction during sports activities. Overtime, these cartilage defects which do not always produce immediate symptoms, could lead to severe clinical pathologies. The emergence of induced pluripotent stem cells (iPSCs) has revolutionized the field of regenerative medicine, providing a promising platform for generating various cell types for therapeutic applications. Thus, chondrocytes differentiated from iPSCs become a promising avenue for non-invasive clinical interventions for cartilage injuries and diseases. In this review, we aim to highlight the current strategies used for in vitro chondrogenic differentiation of iPSCs and to explore their multifaceted applications in disease modeling, drug screening, and personalized regenerative medicine. Achieving abundant functional iPSC-derived chondrocytes requires optimization of culture conditions, incorporating specific growth factors, and precise temporal control. Continual improvements in differentiation methods and integration of emerging genome editing, organoids, and 3D bioprinting technologies will enhance the translational applications of iPSC-derived chondrocytes. Finally, to unlock the benefits for patients suffering from cartilage diseases through iPSCs-derived technologies in chondrogenesis, automatic cell therapy manufacturing systems will not only reduce human intervention and ensure sterile processes within isolator-like platforms to minimize contamination risks, but also provide customized production processes with enhanced scalability and efficiency.
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Diferenciación Celular , Condrogénesis , Células Madre Pluripotentes Inducidas , Medicina de Precisión , Medicina Regenerativa , Humanos , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , Medicina Regenerativa/métodos , Medicina de Precisión/métodos , Condrocitos/citología , Condrocitos/metabolismo , AnimalesRESUMEN
Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder in children, and liver involvement in LCH is rare. This retrospective study reported the clinical features and prognosis of patients with hepatic LCH. Liver involvement was defined by histopathological findings, liver dysfunction or abnormalities, or ultrasound imaging. A total of 130 patients (14.5%) with hepatic LCH out of 899 in the LCH population were enrolled. Patients with liver involvement had greater frequencies of skin, lung, hearing system, and haematologic system involvement, and hemophagocytic lymphohistiocytosis (P<0.001, 0.001, 0.002, 0.009, and <0.001, respectively). Overall survival and progression-free survival were lower in LCH patients with liver involvement than in those without liver involvement (P<0.001 and <0.001). In patients with liver involvement, the overall survival (OS) and progression-free survival (PFS) rates were lower in patients with cholangitis than in those without cholangitis (P<0.020 and 0.030). For the treatment response, the response rate of hepatic LCH patients to initial first-line therapy (n=89) was 22.5%. However, there was no significant difference in the response rate or recurrence rate between patients who shifted from first-line treatment to second-line treatment (n=29) or to targeted therapy (n=13) (P=0.453 and 1.000). The response rate of hepatic LCH patients who received initial second-line therapy (n=13) was 38.5%. Two of these patients subsequently experienced bone recurrence. The response rate of hepatic LCH patients who received initial targeted therapy (n=16) was 75.0%. Three patients subsequently experienced recurrence, including 2 in the bone and 1 in the liver and skin. A total of 39.3% of patients who received second-line treatment had severe myelosuppression (grade III-IV), and 50.8% had varying degrees of gastrointestinal events, whereas there was no severe toxicity in patients who received first-line treatment and targeted therapy. Four patients underwent liver transplantation because of liver cirrhosis. The patients' liver disease improved within a follow-up period of 18-79 months. This study demonstrated that LCH with liver involvement, especially cholangitis, indicates a poor prognosis. Targeted therapy provides a good treatment response and less toxicity. However, it may relapse after withdrawal. Liver transplantation is still a reliable salvage option for patients with end-stage liver disease.
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Histiocitosis de Células de Langerhans , Hepatopatías , Humanos , Histiocitosis de Células de Langerhans/complicaciones , Histiocitosis de Células de Langerhans/mortalidad , Masculino , Femenino , Estudios Retrospectivos , Preescolar , Lactante , Niño , Hepatopatías/etiología , Resultado del Tratamiento , Adolescente , PronósticoRESUMEN
OBJECTIVES: Anthracycline-induced cardiotoxicity is a debilitating cardiac dysfunction for which there are no effective treatments, making early prevention of anthracycline-induced subclinical cardiotoxicity (AISC) crucial. High-density lipoprotein cholesterol (HDL-C) plays a role in cardioprotection, but its impact on AISC remains unclear. Our study aims to elucidate the protective capacity of HDL-C in AISC in patients with diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP (cyclophosphamide, vincristine, doxorubicin, prednisone and rituximab). DESIGN: Prospective observational study. SETTING: Conducted in China from September 2020 to September 2022. PARTICIPANTS: 70 chemotherapy-naïve patients newly diagnosed with DLBCL who were scheduled to receive the standard dose of R-CHOP; 60 participants included in a case-control study (DOI: 10.1186/s12885-022-10085-6). PRIMARY OUTCOME MEASURES: Serum biomarkers, 2D speckle tracking echocardiography and conventional echocardiography were measured at baseline, at the end of the third and sixth cycles of R-CHOP and 6 and 12 months after chemotherapy. RESULTS: 24 patients experienced AISC, while 10 did not. 36 patients were lost to follow-up and death. Cox regression analysis showed that higher levels of HDL-C were associated with a significantly lower risk of AISC (unadjusted HR=0.24, 95% CI 0.09 to 0.67, p=0.006; adjusted HR=0.27, 95% CI 0.09 to 0.79, p=0.017). Patients without AISC had a more stable and higher HDL-C level during the follow-up period. HDL-C levels significantly decreased from the end of the third cycle of chemotherapy to the end of the sixth cycle of chemotherapy in all patients (p=0.034), and particularly in the AISC group (p=0.003). The highest level of HDL-C was significantly higher in patients without AISC than in those with AISC (1.52±0.49 vs 1.22±0.29, p=0.034). CONCLUSIONS: Our study suggests that higher HDL-C levels may associate with lower AISC risk in patients with DLBCL treated with R-CHOP. HDL-C could be a cardioprotective target, but further research is needed to confirm its benefits and limitations. STUDY REGISTRATION NUMBER: Study registration number: ChiCTR2100054721.
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Antraciclinas , Cardiotoxicidad , HDL-Colesterol , Linfoma de Células B Grandes Difuso , Humanos , Antraciclinas/toxicidad , Antibióticos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Azidas , Cardiotoxicidad/etiología , Cardiotoxicidad/prevención & control , Estudios de Casos y Controles , Ciclofosfamida/uso terapéutico , Cimarina/análogos & derivados , Doxorrubicina/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Prednisona/uso terapéutico , Rituximab/uso terapéutico , Vincristina/uso terapéuticoRESUMEN
SnTe-In2Te3 alloys ensure excellent electrical properties in the whole temperature region due to the resonant level. Nevertheless, temperature-sensitive resonance states and single phonon scattering restrict further improvement of thermoelectric performance. Consequently, it is anticipated that additional electrically independent scattering sources should be introduced to impede phonon transport. Here, the SnTe-In2Te3-GeMnTe2 alloy is prepared by further solidifying cubic GeMnTe2, which demonstrates multiple modulation effects. The highly redissolved Mn2+ promotes the valence band convergence, enhances the Seebeck coefficient at higher temperature, and balances the possible weakened resonance level effect at higher carrier concentrations, and a high average power factor (1.94 mW m-1 K-2) is realized over the entire temperature range. Additionally, compensatory vacancies, substitutions, and Ge/Mn precipitates are easily constructed with GeMnTe2 alloying, leading to a further reduction in lattice thermal conductivity, which reaches κl â¼ 0.6 W m-1 K-1 at 850 K. Ultimately, a high peak zT of â¼1.25 (850 K) and a zTave of 0.72 (300-850 K) are realized in (SnTe)2.91(In2Te3)0.03(Ge0.5Mn0.5Te)1.2, and the maximum thermoelectric conversion efficiency of â¼2.8% (ΔT â¼ 450 K) is achieved. The present results indicate multiple effects of GeMnTe2 in enhancing the thermoelectric performance of SnTe-In2Te3 alloys.
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PURPOSE: To analyze the clinical characteristics of peripheral Epstein-Barr virus(EBV)-infected lymphocyte subtypes in children with chronic active EBV infection(CAEBV). METHODS: The levels of peripheral EBV infection of CD4 + T cells, CD8 + T cells, and CD56 + NK cells were determined by flow cytometry and qPCR in patients with CAEBV from July 2017 to July 2022. RESULTS: A total of 112 children with CAEBV were evaluated in the study. Of them, CD4 + type, CD8 + type, and CD56 + type were defined in 44, 21, and 47 patients, respectively. Patients with CD8 + T-cell type had a significantly higher frequency of rash, while hepatomegaly was more common in patients with CD4 + T-cell type. Generally, patients with CD8 + T-cell type had the lowest overall survival(OS) rate(P = 0.017). As for treatment, patients treated with chemotherapy and hematopoietic stem cell transplantation had a better prognosis(P = 0.001). In multivariate analysis, rash, HLH, CD8 + T-cell type, and no decrease of plasma EBV-DNA after treatment were indicated as independent factors of poor prognosis(P = 0.002, 0.024, 0.022, and 0.012, respectively). CONCLUSION: In children with CAEBV, the rash was more frequent in patients with CD8 + T-cell type, whereas patients with CD4 + T-cell type were more likely to develop hepatomegaly. Patients with CD8 + T-cell type had a poor prognosis despite receiving chemotherapy or further HSCT.
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To review and summarize the clinical features, treatment strategies, and prognosis of subcutaneous panniculitis-like T-cell lymphoma complicated with hemophagocytic lymphohistiocytosis (SPTCL-HLH). We searched the Web of Science, Embase, Cochrane Library, and PubMed databases. The keywords were subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis or hemophagocytic syndrome. The patients were divided into a mutated group and a wild-type group based on the existence of HAVCR2 gene mutation. A total of 45 reports, including 63 patients with SPTCL-HLH, were included in the systematic review. Twelve patients detected gene mutations, including 11 with the HAVCR2 gene mutation and 1 with the STXBP2 gene mutation. Thirty-one patients were tested for autoantibodies. Compared with the wild-type group, patients in the mutated group were younger (p = 0.017), and the autoantibody-positive rate was higher (p = 0.006). The main treatment target of 17 patients was to control HLH, yielding an ORR of 88.2%. Two cases relapsed, and both were treated with corticosteroid monotherapy. The corticosteroid monotherapy experienced a higher recurrence rate than the corticosteroids plus other immunoregulatory agents therapy (66.7 vs. 0.0%, p = 0.029). Eighteen patients received initial anthracycline-based chemotherapy, and 50.0% reached remission. The ORR of initial chemotherapy aiming at controlling HLH was higher than those of anthracycline-based chemotherapy (p = 0.015). The ORR was higher in patients initially controlled for HLH versus chemotherapy without HLH control first (90.5 vs. 61.5%, p = 0.024). Interestingly, one patient with juvenile idiopathic arthritis developed SPTCL-HLH during tocilizumab therapy, discontinuing tocilizumab led to a remission of the disease spontaneously. Sixteen patients received stem cell transplantation (SCT). Fifteen patients, including 5 with relapsed/refractory SPTCL-HLH, responded well and survived after receiving SCT. One case who received a sibling-identical SCT relapsed. Further analysis revealed a homozygous HAVCR2 mutation with the donor. The 2-year overall survival (OS) was 91.0% ± 4.4%. There was a significant difference in the OS among patients of different age groups, and patients aged 40-60 had the lowest 2-year OS (66.7% ± 19.2%). Patients with HAVCR2 gene mutations are younger and more likely to be misdiagnosed with autoimmune diseases. Initial treatment of corticosteroids plus immunoregulatory agents attaches great significance to avoiding too aggressive therapies. Intensive anthracycline-based chemotherapy such as CHOP or CHOP-like regimens can also induce long-term remission for aggressive disease. SCT is still a reliable strategy currently. In addition, a watch and wait approach is recommended in patients with mild SPTCL-HLH caused by drugs. The occurrence of HLH does not necessarily mean a more rapidly progressive disease and worse prognosis in patients with SPTCL, but older patients with SPTCL-HLH may be associated with a lower survival rate.
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Linfohistiocitosis Hemofagocítica , Paniculitis , Humanos , Corticoesteroides , Antraciclinas , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Linfohistiocitosis Hemofagocítica/genética , Paniculitis/complicaciones , Paniculitis/diagnóstico , Paniculitis/tratamiento farmacológicoRESUMEN
BACKGROUND: Current treatment of acute leukemia is based on anthracycline chemotherapy. Anthracyclines, despite improving patient survival, have serious cardiotoxicity and therefore cardiac monitoring should be a priority. The purpose of this study is to explore the possible early predictors of anthracycline-induced subclinical cardiotoxicity(AISC)in acute leukemia patients. METHODS: We conducted a prospective observational study involving 51 patients with acute leukemia treated with anthracycline. Demographic data, clinical variables, echocardiography variables and biochemical variables were collected at baseline and after 3 cycles of chemotherapy. Patients were divided into the AISC and No-AISC groups according to changes of global longitudinal peak systolic strain. Regression models and receiver operating characteristic curve analysis were used to explore the relationship between the variables and AISC. RESULT: 17 of the patients suffered subclinical cardiotoxicity after 3 cycles of anthracycline treatment. Multiple logistic regression analysis showed a significant association of DBil (OR 0.612, 95% CI 0.409-0.916, p = 0.017), TBil (OR 0.841, 95% CI 0.717-0.986, p = 0.033), PLT (OR 1.012, 95% CI 1.002-1.021, p = 0.016) and Glu (OR 1.873, 95% CI 1.009-3.475, p = 0.047) with the development of AISC. After 3 cycles of chemotherapy, there was a significant difference in PLT between the AISC and NO-AISC groups. Moreover, the dynamic changes in PLT from baseline to after 3 cycles of chemotherapy were each statistically significant in the AISC and NO-AISC groups. The combination of PLT and N-terminal pro-B-type natriuretic peptide (NT-proBNP) had the highest area under curves (AUC) for the diagnosis of AISC than PLT and NT-proBNP alone (AUC = 0.713, 95%CI: 0.56-0.87, P = 0.017). CONCLUSION: Total bilirubin (TBil), direct bilirubin (DBil), platelets (PLT) and blood glucose (Glu) are independent influencing factors for AISC in acute leukemia patients receiving anthracycline therapy. Bilirubin may be a protective factor and PLT may be a contributing factor for AISC. The combination of baseline PLT and baseline NT-proBNP shows satisfactory predictive ability for AISC in acute leukemia cases treated with 3 cycles of chemotherapy.
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Antraciclinas , Leucemia Mieloide Aguda , Humanos , Enfermedad Aguda , Antraciclinas/efectos adversos , Antibióticos Antineoplásicos/efectos adversos , Bilirrubina , Biomarcadores , Cardiotoxicidad/etiología , Leucemia Mieloide Aguda/tratamiento farmacológico , Estudios ProspectivosRESUMEN
Background: Langerhans cell histiocytosis (LCH) is a rare myeloid precursor cell inflammatory neoplasia, which agonizes, maims, and even kills patients. Although clinical outcomes have steadily improved over the past decades, the progression/relapse rate of LCH remains high. The purpose of this study was to evaluate the prognostic value of the pre-treatment metabolism parameters of baseline 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG PET/CT) in children with LCH. Methods: This cross-sectional study retrospectively and consecutively included 37 children (24 males and 13 females; median age, 5.1 years; range, 2.4-7.8 years) with pre-treatment 18F-FDG PET/CT from September 2020 to September 2022 in Nuclear Medicine Department, Beijing friendship hospital, Capital Medical University, Beijing, China. These patients were then all admitted to the hospital and diagnosed with LCH by biopsy, in Hematology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China. Five metabolism parameters of 18F-FDG PET/CT were analyzed, including maximum standardized uptake, tumor-to-normal liver standard uptake value ratio, tumor-to-normal bone marrow standard uptake value ratio, sum of metabolic tumor volume (sMTV), and sum of total lesion glycolysis (sTLG) of all lesions. Patients were followed up for at least 1 year or until disease progression/relapse. Univariate and multivariate analyses of progression-free survival was performed. Results: During follow-up, 11 (29.7%) patients had disease progression/relapse. Univariate analysis revealed that the risk organ involvement, the treatment response at the 5th or 11th week, pre-treatment sMTV, and sTLG were significantly associated with progression-free survival (P=0.024, 0.018, 0.006, 0.006, and 0.042, respectively). Multivariate COX analysis revealed that non-response at the 11th week, pre-treatment sMTV >32.55 g/cm3, and sTLG >98.86 g (P=0.002, 0.020, 0.026, respectively) were risk factors for progression-free survival. Conclusions: The baseline metabolism parameters of 18F-FDG PET/CT could be promising imaging biomarkers for predicting prognosis in children with LCH.
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This study aimed to compare the serum levels of 34 cytokines of children with hemophagocytic lymphohistiocytosis (HLH) and explored the specific cytokine pattern of HLH subtypes and the relationship between cytokine levels and prognosis. This retrospective study assessed the clinical data and cytokine levels of newly diagnosed children with HLH in Beijing Children's Hospital, Capital Medical University, from January 2017 to December 2021. A total of 101 children were enrolled in the study. The levels of IFN-γ and IL-18 increased in more than 90% of patients, and MIP-1α, SDF-1α, IP-10, IL-6, IL-8, IL-10, IL-1 RA, and TNF-α increased at different levels in more than 50% of patients. The levels of IL-10 in EBV-HLH increased significantly, followed by IFN-γ and IL-18, while IL-10 and IFN-γ in CAEBV-HLH had a slight increase. Except for IL-10, the levels of IL-6, Eotaxin, IL-13, IL-18, IFN-γ, and MIP-1ß in Rh-HLH increased significantly. F-HLH had significantly high IL-10 levels and a slight increase in IL-13. We showed that various cytokines could assist in differentiating HLH subtypes with ROC curve analysis. When IL-10/IL-6 was 1.37, the sensitivity and specificity of diagnosing EBV-HLH were higher than 80% (AUC = 0.837, p < 0.001). The effect of cytokine ratio on classifying HLH subtypes (17/22, 77.3%) was more significant than the single cytokine (5/22, 22.7%). The 3-year overall survival (OS) rate of children with F-HLH was the lowest during the follow-up. The 3-year OS of patients with EBV-HLH and CAEBV-HLH was significantly higher than that with F-HLH (88.1% ± 5.0% vs. 94.1% ± 5.7% vs. 57.1% ± 14.6%, p = 0.017). Cox proportional hazards model revealed that elevated GM-CSF and MCP-1, as well as CNS involvement, were independent risk factors for poor outcomes for patients with HLH. Various cytokines play important roles in HLH. Different subtypes of HLH have their specific cytokines pattern, and the ratio of cytokines may be more significant in differentiating HLH subtypes than the single one. Elevated GM-CSF and MCP-1 could be useful biomarkers for a poor prognosis for patients with HLH.
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Citocinas , Linfohistiocitosis Hemofagocítica , Niño , Humanos , Interleucina-10 , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Interleucina-18 , Interleucina-6 , Estudios Retrospectivos , Interleucina-13RESUMEN
OBJECTIVE: To analyze the clinical features, treatment, and prognosis of chronic active Epstein-Barr virus infection (CAEBV) with central nervous system (CNS) involvement in children. METHODS: Patients with CAEBV admitted to Beijing Children's Hospital, Capital Medical University, were enrolled in this study from January 2017 to December 2020. They were divided into a CNS group and a non-CNS group based on the presence of CNS involvement. RESULTS: Twenty-two patients developed CNS disease, accounting for 23.9% (22/92) of CAEBV patients in the same period. Of these, only 2 of 22 patients presented initially with neurologic symptoms in the CNS group, and they all improved after treatment. Cerebrospinal fluid (CSF) examination demonstrated normal protein concentration and cell number in all patients with CNS involvement. Only 7 patients were positive for CSF EBV-DNA. Twenty-one patients had neuroimaging abnormalities, such as white matter signal abnormalities, encephalography or calcification. In the CNS group, 7 (31.8%) patients died, including 5 who died of active hemophagocytic lymphohistiocytosis, 1 died of unrelated causes, and 1 died of respiratory failure caused by pulmonary lymphoproliferative disease progression after transplantation. The 3-year overall survival was lower in the CNS group than in the non-CNS group (63.6% ± 11.9% versus 86.9% ± 4.1%, P = 0.027). Hemophagocytic lymphohistiocytosis (HLH) is an independent risk factor for CNS involvement in patients with CAEBV (OR = 2.946, 95% CI: 1.042-8.335, P = 0.042). Compared with the non-CNS group, blood EBV-DNA loads and CD4+/CD8+ ratio of T lymphocytes in the CNS group were higher (P < 0.001), while fibrinogen levels and natural killer (NK)-cell activity were lower (P = 0.047). Children with CAEBV were more likely to develop CNS diseases with low NK-cell activity (NK-cell activity < 14.00%, P = 0.023) or high alanine aminotransferase (ALT) levels (ALT levels > 40 U/L, P = 0.032). CONCLUSION: CAEBV with CNS involvement has nonspecific clinical manifestations, laboratory data, neuroimaging but has a worse prognosis. Blood fibrinogen levels and NK-cell activity in CAEBV children with CNS involvement are lower than in those without CNS involvement. In contrast, blood EBV-DNA loads and CD4+/CD8+ ratio of T lymphocytes are higher. Children with CAEBV who presented with HLH, NK-cell activity <14.00%, serum ALT >40 U/L and high-blood EBV-DNA loads are prone to develop CNS diseases.
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Enfermedades del Sistema Nervioso Central , Infecciones por Virus de Epstein-Barr , Niño , Humanos , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4 , Sistema Nervioso Central , FibrinógenoRESUMEN
Bendamustine plus rituximab (BR) and rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) have been shown to be effective in the treatment of indolent B-cell lymphomas (iBCL). The survival outcomes and adverse events of BR and R-CHOP are still controversial, thus we did a systematic review and meta-analysis to assess them. We searched articles in Pubmed, Cochrane, Embase and Web of Science comparing BR to R-CHOP in patients with iBCL. A total of 3141 patients were included. The results of our meta-analysis revealed that BR has the potential of improving PFS (HR = 0.67, p = 0.03). No apparent benefit of BR was noted in patients with iBCL for OS (HR = 1.18, p = 0.04). Compared with R-CHOP, we found that BR regimen had the potential of prolonging PFS, minor toxicity, a better quality of life, and better cost-effectiveness. These results supported BR as a preferred first-line treatment option for patients (especially for elders) with iBCL.
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Linfoma de Células B , Calidad de Vida , Humanos , Anciano , Rituximab/uso terapéutico , Clorhidrato de Bendamustina/uso terapéutico , Vincristina/efectos adversos , Ciclofosfamida/efectos adversos , Prednisona/uso terapéutico , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/inducido químicamente , Doxorrubicina/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
BACKGROUND: Anthracycline-induced cardiotoxicity is an irreversible cardiac cell injury. Therefore, it's very important to identify influencing factors of anthracycline-induced subclinical cardiotoxicity (AISC). This study was designed to analyze the influencing factors of AISC in patients with diffuse large B-cell lymphoma (DLBCL) treated with the (R)-CHOP chemotherapy regimen. METHODS: This is an ongoing observational prospective clinical trial. All patients underwent conventional echocardiography and speckle tracking echocardiography at the time of enrollment and during treatment. Changes of global longitudinal peak systolic strain were assessed after 3 cycles of (R)-CHOP chemotherapy, and patients were divided into the AISC and No-AISC groups. Demographic data, clinical variables, and biochemical variables were measured. Regression models, receiver operating characteristic curve analysis, and difference values were used to explore the relationships between variables and AISC. RESULTS: Among 70 patients who completed 3 cycles of (R)-CHOP chemotherapy, 26 developed AISC. In multiple logistic regression, HDL-C (P = 0.047), ApoA1 (P = 0.022), TG (P = 0.029) and e' (P = 0.008) were associated with AISC. The combination of HDL-C and NT-proBNP had the highest area under curves (AUC) for the diagnosis of AISC than HDL-C and NT-proBNP alone (AUC = 0.752, 95%CI: 0.63-0.87, P = 0.001). Between the No-AISC and AISC groups, there was no significant difference in HDL-C, ApoA1, and e' at baseline and after 3 cycles of chemotherapy, respectively. The dynamic changes of HDL-C, ApoA1, and e' from baseline to the end of the 3rd cycle of chemotherapy showed statistically significant differences. CONCLUSIONS: HDL-C, ApoA1, TG, and e' are independent predictive factors in DLBCL cases treated with the (R)-CHOP chemotherapy regimen. The combination of HDL-C and NT-proBNP may improve the predictive ability for AISC in patients with DLBCL administered 3 cycles of (R)-CHOP chemotherapy. Dynamic changes of HDL-C, ApoA1, and e' may be meaningful for predicting AISC. TRIAL REGISTRATION: Our study was registered in the Chinese Clinical Trial Registry (Approval ID. ChiCTR2100054721 http://www.chictr.org.cn/showproj.aspx?proj=145082 ).
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Antraciclinas , Linfoma de Células B Grandes Difuso , Antraciclinas/efectos adversos , Antibióticos Antineoplásicos/uso terapéutico , Cardiotoxicidad/tratamiento farmacológico , Cardiotoxicidad/etiología , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Estudios ProspectivosRESUMEN
OBJECTIVE: To analyze the clinical significance of soluble CD25 (sCD25) levels in cerebrospinal fluid (CSF) in pediatric hemophagocytic lymphohistiocytosis (HLH) with central nervous system (CNS) involvement. METHODS: All patients diagnosed with HLH admitted to Beijing Children's Hospital, Capital Medical University between January 1, 2017 and October 31, 2021 who received a measurement of their HLH-related parameters and CSF sCD25 levels at admission were enrolled in this study. RESULTS: CSF sCD25 levels in patients with primary HLH were higher than those in patients with Epstein-Barr virus infection-associated HLH, and the median level was 444 pg/ml. The difference in CSF sCD25 levels between the non-CNS group and the CNS group was statistically significant (591 [259-33,643] pg/ml vs. 123 (36-437) pg/ml, p < .001). The best cutoff value of CSF sCD25 was 273.5 pg/ml (AUC = 0.987, 95% CI: 0.972-1.000), with sensitivity, specificity, positive predictive values, and negative predictive values of 96.4%, 92.8%, 81.8%, and 98.7%, respectively. CSF sCD25 in the severe CNS involvement group was significantly higher than that in the nonsevere CNS involvement group (p = .014). The 3-year overall survival (OS) of patients with high CSF sCD25 levels was lower than that of patients with low CSF sCD25 levels(71.6% ± 8.1% vs. 93.3% ± 2.9%, hazard ratio [HR] = 3.637, p = .003). CONCLUSION: Increased CSF sCD25 levels in active disease can predict CNS-HLH. Primary HLH has a higher CSF sCD25 level than Epstein-Barr virus infection-associated HLH. Patients who are diagnosed with CNS-HLH with CSF sCD25 levels higher than 273.5 pg/ml are more likely to develop severe CNS involvement, suggesting a poor prognosis.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Linfohistiocitosis Hemofagocítica , Sistema Nervioso Central , Niño , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4 , Humanos , Linfohistiocitosis Hemofagocítica/complicaciones , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
BACKGROUND: A lack of demographic and clinical data hinders efforts of health care providers in China to support patients with type 1 diabetes mellitus (T1D). Therefore, the aim of the present retrospective study was to provide an overview of the demographic and clinical characteristics of Chinese patients with T1D. METHODS: Hospital medical records of patients with T1D (diagnosed between January 2000 and December 2011) in 105 secondary and tertiary hospitals across Guangdong province were reviewed. Data were collected on patient age at diagnosis, presentations at onset, physical examination, and diabetes management. RESULTS: In all, 3173 patients diagnosed with T1D between January 2000 and December 2011 were included in the study (46.2% female). The median age at diagnosis was 27.5 years (interquartile range [IQR] 18.0-38.0) years and the median body mass index (BMI) at onset was 19.6 kg/m2 (IQR 17.4-21.8 kg/m2 ). Among adult patients, 0.9% were obese, 6.6% were overweight, 62.3% were normal weight, and 30.3 % were underweight. The prevalence of diabetic ketoacidosis (DKA) at onset was 50.1%. The proportion of patients with retinopathy, nephropathy, and neuropathy was 8.1%, 20.7 %, and 11.1%, respectively. CONCLUSION: The adult-onset form of T1D is not rare in China. The registry participants were characterized by older age at onset, lower BMI, and a higher prevalence of DKA at onset compared with those in regions with a high incidence of T1D, such as northern Europe. These findings contribute to a better understanding of the heterogeneity of T1D in different populations and so will help healthcare providers to develop management models that are more suitable for these patients.
Asunto(s)
Demografía , Diabetes Mellitus Tipo 1/epidemiología , Sistema de Registros , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , China/epidemiología , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: To investigate the glycemic control and the related factors of type 1 diabetic patients in Guangdong Province. METHODS: Medical records and blood samples of type 1 diabetic patients were collected in 89 tertiary and secondary hospitals from all of the 21 cities in Guangdong Province. The clinical data were analyzed to explore the correlates of glycemic control. HbA1c levels, measured in Guangdong Diabetes Center, were used to assess glycemic control. RESULTS: 851 patients were enrolled from August 6, 2010 to May 25, 2011. There were 408 males and 443 females. The median (interquartile range) age was 29.6 years (20.3 - 41.3 years). The onset age of diabetes was 25.3 years (15.7 - 35.5 years). The disease duration was 3.3 years (1.0 - 7.3 years). The BMI was 19.9 kg/m(2) (17.9 - 21.8 kg/m(2)). HbA1c levels were 8.6% (6.9% - 11.0%) and only 234 (27.50%) patients reached the age-specific target levels. Correlates with poorer glycemic control were 13 - 19 years old (vs 7 - 12 and ≥ 20 years old), lower household income, not on dietary intervention, never accepting diabetic education and shorter diabetic duration. CONCLUSION: The majority of Guangdong type 1 diabetic patients did not achieve target values for glycemic control, indicating an urgent need for comprehensive management to improve glycemic control.