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1.
Artigo em Inglês | MEDLINE | ID: mdl-34595543

RESUMO

PURPOSE: To analyze the genetic and clinical features of children with MAP2K1-mutated Langerhans cell histiocytosis (LCH). METHODS: We compared the clinical features of 37 children with MAP2K1-mutated LCH with those of the BRAFV600E mutation group (n = 133) and no known mutation group (n = 59) in the same period. RESULTS: We found 13 mutations of the MAP2K1 gene, which were mainly concentrated at p.53-62 and p.98-103. The most common mutation site was c.172_186del (12/37). Compared with the BRAFV600E mutation group, the patients with MAP2K1 mutations were mainly characterized by single-system multiple bone involvement (P = 0.022), with later disease onset (P = 0.029) as well as less involvement of risk organs, especially liver (P = 0.024). There was no significant difference in clinical features compared with the no known mutation group. The 2-year progression-free survival rate of first-line treatment (ChiCTR1900025783, 07/09/2019) in MAP2K1-mutated patients was 65.6% ± 9.5%. The prognosis of patients with lung involvement was poor [HR (95% CI) = 6.312 (1.769-22.526), P = 0.005]. More progression or relapses could be found in patients with bony thorax involvement (8/17 vs. 2/20, P = 0.023), yet involvements in other sites of bones, such as craniofacial bone involvement (8/26 vs. 2/11, P = 0.688) and limb bone involvement (5/12 vs. 5/25, P = 0.240), were not correlated to disease progression or relapse. CONCLUSION: The children with MAP2K1-mutated LCH have specific clinical features requiring clinical stratification and precise treatment. MAP2K1-mutated patients with lung involvement (especially with bony thorax involvement) had poor prognosis.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34654782

RESUMO

ABSTRACT: In the context of diabetes mellitus, various pathological changes cause tissue ischemia and hypoxia, which can lead to the compensatory formation of neovascularization. However, disorders of the internal environment and dysfunctions of various cells contribute to the dysfunction of neovascularization. Although the problems of tissue ischemia and hypoxia have been partially solved, neovascularization also causes many negative effects. In the process of small blood vessel renewal, pericytes are extremely important for maintaining the normal growth and maturation of neovascularization. Previously, our understanding of pericytes was very limited, and the function of pericytes was not yet clear. Recently, multiple new functions of pericytes have been identified, affecting various processes in angiogenesis and relating to various diseases. Therefore, the importance of pericytes has gradually become apparent. This article presents the latest research progress on the role of pericytes in diabetic angiogenesis, characterizes pericytes, summarizes various potential therapeutic targets, and highlights research directions for the future treatment of various diabetes-related diseases.

4.
Cytokine ; 149: 155729, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34673333

RESUMO

OBJECT: Goal of this research was to investigate values of serum cytokines in childhood HLH with different triggers, with the expectation to find secretion spectrum of 5 main types of underlying diseases. METHOD: 118 newly diagnosed HLH were included, and serum concentrations of 6 cytokines were tested before treatment began. Absolute cytokine levels and ratios between them were then studied in the HLH groups collectively and separately RESULTS: In general, IFN-γ, IL-10 and IL-6 showed differences among 5 HLH groups. Specifically, relative levels of these three cytokines to each other were meaningful in distinguishing 4 types of HLH. Level of IL-6 was higher than those of IFN-γ or IL-10 in HLH driven by Systemic auto-inflammatory disorders (SAIDs) or Langerhans Cell Histiocytosis (LCH), while primary HLH and EBV-HLH shared elevated ratio of IL-10 to IL-6. Although more than one distinctive ratios were found in 3 HLH groups, combination of these parameters didn't offer optimal balance between sensitivity and specificity. CONCLUSION: As a group of easily gained laboratory findings, cytokine levels were reliable in the procedure of roughly classifying HLH cases with the help of patients' clinical phenotype. However, adequate data is still needed to explore the significance of these indicators in identifying one particular underlying disease accurately.

5.
Small ; : e2102485, 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34605169

RESUMO

The therapeutic potential of nanomaterials toward oxidative damage relevant diseases has attracted great attentions by offering promising advantages compared with conventional antioxidants. Although different kinds of nanoantioxidants have been well developed, the facile fabrication of robust and efficient nanoscavengers is still met with challenges like the use of toxic and high-cost subunits, the involvement of multistep synthetic process, and redundant purification work. Herein, a direct fabrication strategy toward polyphenol nanoparticles with tunable size, excellent biocompatibility, and reactive oxygen species (ROS) scavenging capacities from grape seed via an enzymatic polymerization method is reported. The resulting nanoparticles can efficiently prevent cell damage from ROS and exert promising in vivo antioxidant therapeutic effects on several oxidative stress-related diseases, including accelerating wound healing, inhibiting ulcerative colitis, and regulating the oxidative stress in dry eye disease. This study can stimulate the development of more kinds of low-cost, safe, and efficient biomass-based antioxidative nanomaterials via similar fabrication methodologies.

6.
Pediatr Investig ; : e12282, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34540320

RESUMO

Importance: The Coronavirus disease 2019 (COVID-19) global pandemic poses a considerable challenge for pediatricians. Objective: This study aimed to identify the epidemiological characteristics and clinical features of pediatric patients with COVID-19 in China. Methods: This multicenter retrospective study included pediatric patients from 46 hospitals in China, covering 12 provinces and two municipalities. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were analyzed. Results: In total, 211 pediatric patients with COVID-19 were included in this study. The median age was 7.0 years (range: 22 days to 18 years). Approximately 16.3% of the patients exhibited asymptomatic infections, 23.0% had upper respiratory tract infections, and 60.7% had pneumonia, including two with severe pneumonia and one with critical illness. Approximately 78.7% of the pediatric patients occurred in familial clusters. The most three common symptoms or signs at onset in children with COVID-19 were fever (54.5%), cough (49.3%), and pharyngeal congestion (20.8%). Only 17.6% of the patients presented with decreased lymphocyte count, whereas 13.6% had increased lymphocyte count. Among the patients with pneumonia who exhibited abnormal chest computed tomography findings, 18.2% (23/127) of the patients had no other symptoms. Generally, the chest radiographs showed abnormalities that affected both lungs (49.6%); ground-glass opacity (47.2%) was the most common manifestation. The cure and improvement rates were 86.7% (183/211) and 13.3% (28/211), respectively. Only one patient with an underlying condition received invasive mechanical ventilation; none of the patients died. Interpretation: Similar to adults, children of all age groups are susceptible to COVID-19. Fortunately, most pediatric patients have mild symptoms or remain asymptomatic, despite the high incidence of pneumonia. Decreased proportions of white blood cells and lymphocytes are less frequent in children than in adults.

7.
ACS Appl Mater Interfaces ; 13(33): 39126-39134, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34383476

RESUMO

The usage of exogenous antioxidant materials to relieve oxidative stress offers an important strategy for the therapy of oxidative stress-induced injuries. However, the fabrication processes toward the antioxidant materials usually require the involvement of extra metal ions and organic agents, as well as sophisticated purification steps, which might cause tremendous environmental stress and induce unpredictable side effects in vivo. To address these issues, herein, we proposed a novel strategy to fabricate green nanoparticles for efficiently modulating oxidative stress, which was facilely prepared from tea polyphenol extracts (originated from green tea) via a green enzymatic polymerization-based chemistry method. The resulting nanoparticles possessed a uniform spherical morphology and good stability in water and biomedium and demonstrated excellent radical scavenging properties. These nanoparticle scavengers could effectively prevent intracellular oxidative damage, accelerate wound recovery, and protect the kidneys from reactive oxygen species damaging in the acute kidney injury model. We hope this work will inspire the further development of more types of green nanoparticles for antioxidant therapies via similar synthetic strategies using green biomass materials.


Assuntos
Injúria Renal Aguda/prevenção & controle , Antioxidantes/química , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/química , Chá/química , Células 3T3 , Células A549 , Animais , Antioxidantes/farmacologia , Catecóis/química , Sobrevivência Celular/efeitos dos fármacos , Feminino , Sequestradores de Radicais Livres/metabolismo , Química Verde , Peroxidase do Rábano Silvestre/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Peróxido de Hidrogênio/química , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina Teranóstica , Cicatrização/efeitos dos fármacos
8.
Front Cell Infect Microbiol ; 11: 663884, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277466

RESUMO

Background: The pandemic of Coronavirus Disease 2019 (COVID-19) brings new challenges for pediatricians, especially in the differentiation with non-COVID-19 pneumonia in the peak season of pneumonia. We aimed to compare the clinical characteristics of pediatric patients with COVID-19 and other respiratory pathogens infected pneumonias. Methods: We conducted a multi-center, cross-sectional study of pediatric inpatients in China. Based on pathogenic test results, pediatric patients were divided into three groups, including COVID-19 pneumonia group, Non-COVID-19 viral (NCV) pneumonia group and Non-viral (NV) pneumonia group. Their clinical characteristics were compared by Kruskal-Wallis H test or chi-square test. Results: A total of 636 pediatric pneumonia inpatients, among which 87 in COVID-19 group, 194 in NCV group, and 355 in NV group, were included in analysis. Compared with NCV and NV patients, COVID-19 patients were older (median age 6.33, IQR 2.00-12.00 years), and relatively fewer COVID-19 patients presented fever (63.2%), cough (60.9%), shortness of breath (1.1%), and abnormal pulmonary auscultation (18.4%). The results were verified by the comparison of COVID-19, respiratory syncytial virus (RSV) and influenza A (IFA) pneumonia patients. Approximately 42.5%, 44.8%, and 12.6% of the COVID-19 patients presented simply ground-glass opacity (GGO), simply consolidation, and the both changes on computed tomography (CT) scans, respectively; the proportions were similar as those in NCV and NV group (p>0.05). Only 47.1% of COVID-19 patients had both lungs pneumonia, which was significantly lower than that proportion of nearly 80% in the other two groups. COVID-19 patients presented lower proportions of increased white blood cell count (16.5%) and abnormal procalcitonin (PCT) (10.7%), and a higher proportion of decreased lymphocyte count (44.0%) compared with the other two groups. Conclusion: Majority clinical characteristics of pediatric COVID-19 pneumonia patients were milder than non-COVID-19 patients. However, lymphocytopenia remained a prominent feature of COVID-19 pediatric pneumonia.


Assuntos
COVID-19 , Pneumonia , Criança , China/epidemiologia , Estudos Transversais , Humanos , Pulmão/diagnóstico por imagem , Pneumonia/epidemiologia , Estudos Retrospectivos , SARS-CoV-2
9.
Orphanet J Rare Dis ; 16(1): 314, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34266467

RESUMO

OBJECTIVE: To evaluate the clinical efficacy of haploidentical haematopoietic stem cell transplantation (haplo-HSCT) for the treatment of malignant infantile osteopetrosis (MIOP) and intermediate osteopetrosis. METHODS: Children with MIOP and IOP who underwent haplo-HSCT in Beijing Children's Hospital, Capital Medical University, from January 2010 to May 2018 were retrospectively analysed. Data relating to the clinical manifestations, engraftment, and prognosis of the children were extracted from medical records. RESULTS: Twenty-seven patients, including 18 males and 9 females, with an onset age of 12 (0.04-72) months were enrolled in this study. The median time from diagnosis to transplantation was 4 (1-23) months. All patients received haplo-HSCT with a myeloablative conditioning regimen (including fludarabine, busulfan, and cyclophosphamide). Graft versus host disease (GVHD) prophylaxis was based on anti-human T lymphocyte porcine immunoglobulin/anti-human thymus globulin, methotrexate, and mycophenolate mofetil. The median observation time was 55.2 (0.3-126.2) months. By the end of follow-up, twenty patients survived and seven patients died. The 5 year overall survival rate was 73.9%. Stage I-II acute GVHD was observed in 20 patients, stage III GVHD in 1 patient and no patients had stage IV disease. Chronic GVHD was observed in 11 patients (40.7%) and was controlled by anti-GVHD therapy. CONCLUSIONS: Haplo-HSCT was an effective treatment for MIOP and IOP, with a high survival rate and significantly improved clinical symptoms. For patients with a vision impairment before HSCT, the improvement was slow after transplantation. The incidence of GVHD was high but mild and was effectively controlled by appropriate treatment. These data indicated that haplo-HSCT was a feasible treatment for MIOP and IOP.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Osteopetrose , Animais , Criança , Feminino , Humanos , Lactente , Masculino , Osteopetrose/terapia , Estudos Retrospectivos , Suínos , Condicionamento Pré-Transplante
10.
J Pediatr ; 2021 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-34260897

RESUMO

OBJECTIVE: To analyze the clinical characteristics, prognosis factors and risk factors of chronic active Epstein-Barr virus infection in children. STUDY DESIGN: Observational analysis of baseline data and follow-up evaluation data of children with chronic active Epstein-Barr virus infection in our center between January 1, 2016 and December 31, 2019; they were followed through June 30, 2020. RESULTS: There were 96 children with chronic active Epstein-Barr virus infection (50 male and 46 female children), with the median age of 6.7 years (range from 0.6 to 17.6 years) at diagnosis. The median follow-up time was 16.5 months. The 3 most common clinical manifestations were fever, lymph node enlargement, and hepatomegaly or splenomegaly. Thirty-three patients (36.3%) also had a diagnosis of hemophagocytic lymphohistiocytosis (HLH). Epstein-Barr virus infected only T lymphocytes, natural killer cells, or both T- and natural killer-cell types in 15 (33.3%), 17 (37.8%), and 13 (28.9%), respectively. At the end of follow-up, 26 children had died, 60 survived, and 10 were lost to follow-up. Generally, progression-free survival was 69.8% ± 2.4%. The level of interleukin (IL)-6 and IL-10 and the combination of younger age and lower pathologic grade at diagnosis were independent prognostic factors by Cox regression analysis (P = .009 and .018, respectively). CONCLUSIONS: Children with lower levels of IL-6 and IL-10, or with younger age and lower pathologic grades, generally had favorable outcomes at the terminal point of follow-up, indicating better prognostic signs.

11.
Pituitary ; 2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34302575

RESUMO

PURPOSE: Langerhans cell histiocytosis (LCH) can affect any organ. Central nervous system (CNS) involvement is rare, and its management is poorly understood. This study aimed to analyze the clinical response and prognosis of pediatric LCH with central diabetes insipidus (CDI) treated with second-line therapy with cytarabine (Ara-c), cladribine (2-cdA), dexamethasone, and vindesine. METHODS: This retrospective case series study included pediatric LCH with CDI treated at Beijing Children's Hospital affiliated with Capital Medical University (11/2012-01/2018). After the first-line 2009-LCH regimen, patients with active disease/worse response, relapse, or no significant improvement in risk organs, pituitary, or lung were given the second-line therapy. Baseline characteristics, clinical response and adverse reactions were observed. RESULTS: Twenty-six children with CDI and disappearance of hyperintensity in the posterior pituitary were included. They received "Regimen A" Ara-c + dexamethasone + vindesine (n = 7) or "Regimen B" Ara-c + dexamethasone + vindesine + 2-cdA (n = 19) as second-line therapy. There were 14 patients with CDI but without pituitary stalk thickening (PST) and 12 with CDI and PST. In patients with CDI alone, 4/4 patients receiving Regimen A and 3/10 receiving Regimen B improved. All patients with CDI and PST showed improvement for PST. The reappearance of hyperintensity at the posterior pituitary was observed in 10 patients with CDI. All 26 children were alive after a median follow-up of 40.5 months. There were no chemotherapy-related deaths. CONCLUSION: A combined therapy with Ara-c, 2-cdA, dexamethasone, and vindesine could partially alleviate pituitary disease conditions in pediatric LCH with CNS involvement, with good tolerance.

12.
J Clin Oncol ; 39(28): 3161-3170, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34077242

RESUMO

PURPOSE: Arsenic combined with all-trans retinoic acid (ATRA) is the standard of care for adult acute promyelocytic leukemia (APL). However, the safety and effectiveness of this treatment in pediatric patients with APL have not been reported on the basis of larger sample sizes. METHODS: We conducted a multicenter trial at 38 hospitals in China. Patients with newly diagnosed APL were stratified into two risk groups according to baseline WBC count and FLT3-ITD mutation. ATRA plus arsenic trioxide or oral arsenic without chemotherapy were administered to the standard-risk group, whereas ATRA, arsenic trioxide, or oral arsenic plus reduced-dose anthracycline were administered to the high-risk group. Primary end points were event-free survival and overall survival at 2 years. RESULTS: We enrolled 193 patients with APL. After a median follow-up of 28.9 months, the 2-year overall survival rate was 99% (95% CI, 97 to 100) in the standard-risk group and 95% (95% CI, 90 to 100) in the high-risk group (P = .088). The 2-year event-free survival was 97% (95% CI, 93 to 100) in the standard-risk group and 90% (95% CI, 83 to 96) in the high-risk group (P = .252). The plasma levels of arsenic were significantly elevated after treatment, with a stable effective level ranging from 42.9 to 63.2 ng/mL during treatment. In addition, plasma, urine, hair, and nail arsenic levels rapidly decreased to normal 6 months after the end of treatment. CONCLUSION: Arsenic combined with ATRA is effective and safe in pediatric patients with APL, although long-term follow-up is still needed.

13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(6): 585-588, 2021 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-34096032

RESUMO

OBJECTIVE: To explore the genetic basis for a fetus with renal abnormalities through whole exome sequencing and imaging examination. METHODS: Clinical data and result of medical imaging of the fetus was collected. Amniotic fluid sample was collected for the extraction of fetal DNA. Whole exome sequencing was carried out. Candidate variants were verified by Sanger sequencing. RESULTS: Prenatal ultrasonography showed that the fetus had bilateral enlargement of the kidneys with hyperechogenicity and diffuse renal cysts. Whole exome sequencing revealed that the fetus carried compound heterozygous variants of the PKHD1 gene, namely c.5137G>T and c.2335_2336delCA, which were derived from its mother and father, respectively. CONCLUSION: The fetus was diagnosed with autosomal recessive polycystic kidney disease through combined prenatal ultrasonography and whole exome sequencing. The compound heterozygous variants of the PKHD1 gene probably underlay the pathogenesis in the fetus. The results have enabled prenatal diagnosis and genetic counseling for its parents.


Assuntos
Rim Policístico Autossômico Recessivo , Feminino , Testes Genéticos , Humanos , Rim Policístico Autossômico Recessivo/diagnóstico por imagem , Rim Policístico Autossômico Recessivo/genética , Gravidez , Diagnóstico Pré-Natal , Receptores de Superfície Celular/genética , Sequenciamento Completo do Exoma
14.
Front Pediatr ; 9: 672547, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178890

RESUMO

Objective: To investigate the clinical characteristics, treatment, and prognosis of children with systemic juvenile xanthogranuloma (JXG). Methods: Clinical data of children with JXG who were hospitalized in Beijing Children's Hospital, Capital Medical University, from January 2012 to December 2019 were retrospectively analyzed, including clinical manifestations, laboratory determinations, treatment, and prognosis of the children. Patients were treated with vindesine + prednisone as the first-line treatment and cytarabine + vindesine + dexamethasone ± cladribine as the second-line treatment. Results: Ten patients, including 8 males and 2 females, with a median of onset age of 1.95 (0.80-7.30) years, exhibited multi-system dysfunction. The median age of diagnosis was 2.45 (1.30-12.10) years. The most common location of extracutaneous lesions was the central nervous system (6 cases), followed by the lung (5 cases) and bone (4 cases). Nine patients underwent first-line chemotherapy, and 6 patients underwent second-line chemotherapy, including 5 patients with poorly controlled disease after first-line treatment. The median observation time was 29 (3-115) months. Nine patients survived, whereas one patient died of respiratory failure caused by pulmonary infection. At the end of follow-up, 7 patients were in active disease (AD)/regression state (AD-better), and 2 patients were in an AD/stable state (AD-stable). Three patients had permanent sequelae, mainly central diabetes insipidus. The rates of response to the first-line treatment and the second-line treatment were 40.0 and 66.7% respectively. Conclusion: The chemotherapy protocol for Langerhans cell histiocytosis (LCH) may be effective for patients with systemic JXG. Central nervous system involvement may not impact overall survival, but serious permanent sequelae may occur.

15.
Orphanet J Rare Dis ; 16(1): 269, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112210

RESUMO

PURPOSE: We intended to investigate the clinical features of paediatric patients with chronic active Epstein-Barr virus infection (CAEBV) and to examine the effectiveness of the L-DEP regimen before haematopoietic stem cell transplantation (HSCT). METHODS: A retrospective analysis was performed on 35 patients with CAEBV at Beijing Children's Hospital from January 2016 to January 2020. The efficacy and adverse events of the L-DEP regimen were evaluated. RESULTS: The median age of the 35 patients was 7.0 years old (range 2.5-17.5 years). Twenty-eight patients achieved a clinical response (80.0%, 22 in clinical CR, 6 in clinical PR) after L-DEP. In terms of virological response, 7 patients (20%) were assessed as having virological CR, and 23 patients (65.7%) had virological PR. Finally, 29 patients underwent allo-HSCT. The median survival time was 18 months (2-50 months). The 3-year overall survival rates in patients treated with chemotherapy only (n = 6) and chemotherapy followed by HSCT (n = 25) were 33.3% and 75.4%, respectively. After L-DEP 1st treatment and L-DEP 2nd treatment, the EBV-DNA loads in blood and plasma were significantly reduced compared with those before chemotherapy (median: 4.29 × 105 copies/ml vs. 1.84 × 106 copies/ml, Mann-Whitney U: P = 0.0004; 5.00 × 102 copies/ml vs. 3.17 × 103 copies/ml, Mann-Whitney U; P = 0.003; 2.27 × 105 copies/ml vs. 1.84 × 106 copies/ml, P = 0.0001; 5.00 × 102 copies/ml vs. 3.17 × 103 copies/ml, P = 0.003). Compared with the liver and spleen size before chemotherapy, the size of the liver and spleen shrank significantly after L-DEP 2nd (median 3.8 cm vs. 1.9 cm, P = 0.003; 3.8 cm vs. 0 cm, P < 0.008). In addition, after L-DEP treatment, there was no difference in the clinical or virological response rate regardless of HLH status (clinical response: 77.3% vs. 84.6%, P = 0.689; virological response: 90.9% vs. 76.9%, P = 0.337). CONCLUSION: The L-DEP regimen is an effective therapy in CAEBV for bridging to allo-HSCT.


Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Adolescente , Criança , Pré-Escolar , Herpesvirus Humano 4 , Humanos , Estudos Retrospectivos , Taxa de Sobrevida
16.
Int J Immunopathol Pharmacol ; 35: 20587384211025934, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34187243

RESUMO

Autoimmune lymphoproliferative syndrome (ALPS) usually presents in childhood with fever, nonmalignant splenomegaly, and lymphadenopathy along with cytopenia, which is caused by mutations in the FAS apoptotic pathway. The TCRαß + CD4/CD8 double-negative T cells (DNT), one of required criteria of ALPS, will rise markedly in ALPS. Human Protein kinase C delta (PRKCD) deficiency (OMIM # 615559) was recently identified to be causative for an ALPS-type III with significant B-cell proliferation particularly of immature B cells. We report a pedigree homozygous variation of PRKCD gene (c.36T>G, p. Y12X) which presented with refractory cytopenia, splenomegaly, and polarization of DNT/regulatory T cells (Treg) axis. After repeated recurrence, the patient was treated with mTOR inhibitor sirolimus, which had a safety mechanism and specifically rebalance the DNT/Treg axis. The patient's hemoglobin and clinical condition improved gradually by the application of sirolimus (1.5 mg/m2, actual blood concentration 4.27-10.3 ng/l). Homozygous variation in PRKCD may lead to typical ALPS clinical manifestations. Targeting DNT/Treg axis, use of sirolimus in such patients may help to achieve good clinical control.

17.
Eur J Pediatr ; 180(11): 3411-3417, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34046719

RESUMO

Chronic immune thrombocytopenia (CITP) is an autoimmune disease with many immune dysfunctions, including T helper type 17 cell (Th17)/regulatory T cells (Tregs) imbalance. Low quality of life and side effects of drugs are severe, especially in pediatrics. This study aimed to determine Th17/Treg polarization in pediatric CITP when first diagnosing ITP and evaluate its use as a predictive marker for pediatric CITP. This was a pilot study from a multi-center. Setting the effective data size to 100 patients, data entry ended in the 142nd patient who had completed a 1-year follow-up. The percentages of Treg cells and Th17 cells were quantified by flow cytometry when new diagnosed ITP patients first arrived. The association between the Th17/Treg ratio and CITP was analyzed statistically. The percentages of Treg cells and Th17 cells were lower (P = 0.0008) and higher (P = 0.0001), respectively, in the CITP-outcome group compared with the remission group. The receiver operating characteristic analysis showed that the area under the curve (AUC) of Treg and Th17 cells was 0.811 and 0.834, respectively. The ratio of Th17/Treg exhibited the largest AUC of 0.897 (cutoff value 0.076).Conclusions: Thus, the percentage of Th17 /Treg ratio of pediatric CITP is elevated at new diagnosed ITP stage. It is a promising predictive marker for the development of CITP to some extent.Trial registration: ChiCTR1900022419 (10th April 2019) What is Known: • The percentage of Th17 /Treg ratio of pediatric CITP is elevated. What is New: • This study shows that the percentage of Th17 /Treg ratio of pediatric CITP is elevated at new diagnosed ITP stage. This work may provide a new point for pediatric CITP's prediction. The imbalanced ratio of Th17/Treg was obvious when first diagnose ITP in pediatric CITP patients, rendering them as potential predictive tools for discriminating CITP to facilitate with the management of pediatric patient care. In addition, the combination of them may serve as a predictive marker in pediatric CITP.


Assuntos
Pediatria , Púrpura Trombocitopênica Idiopática , Criança , Humanos , Projetos Piloto , Púrpura Trombocitopênica Idiopática/diagnóstico , Qualidade de Vida , Linfócitos T Reguladores , Células Th17
18.
Clin Pharmacokinet ; 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34041714

RESUMO

BACKGROUND: Population pharmacokinetic evaluations have been widely used in neonatal pharmacokinetic studies, while machine learning has become a popular approach to solving complex problems in the current era of big data. OBJECTIVE: The aim of this proof-of-concept study was to evaluate whether combining population pharmacokinetic and machine learning approaches could provide a more accurate prediction of the clearance of renally eliminated drugs in individual neonates. METHODS: Six drugs that are primarily eliminated by the kidneys were selected (vancomycin, latamoxef, cefepime, azlocillin, ceftazidime, and amoxicillin) as 'proof of concept' compounds. Individual estimates of clearance obtained from population pharmacokinetic models were used as reference clearances, and diverse machine learning methods and nested cross-validation were adopted and evaluated against these reference clearances. The predictive performance of these combined methods was compared with the performance of two other predictive methods: a covariate-based maturation model and a postmenstrual age and body weight scaling model. Relative error was used to evaluate the different methods. RESULTS: The extra tree regressor was selected as the best-fit machine learning method. Using the combined method, more than 95% of predictions for all six drugs had a relative error of < 50% and the mean relative error was reduced by an average of 44.3% and 71.3% compared with the other two predictive methods. CONCLUSION: A combined population pharmacokinetic and machine learning approach provided improved predictions of individual clearances of renally cleared drugs in neonates. For a new patient treated in clinical practice, individual clearance can be predicted a priori using our model code combined with demographic data.

19.
Mol Cancer Ther ; 20(7): 1316-1323, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33879554

RESUMO

The aim of this study was to investigate the prognostic significance of BRAFV600E in cell-free (cf) DNA (cfBRAFV600E) and lesion tissues (ltBRAFV600E) in pediatric Langerhans cell histiocytosis (LCH). This study included a total of 140 patients with successfully detected cfBRAFV600E and ltBRAFV600E at diagnosis. Treatment response at week 6 was correlated with both cfBRAFV600E and ltBRAFV600E Moreover, the patients with positive cfBRAFV600E had a much lower 3-year progression-free survival (PFS) rate and a higher progression/reactivation rate than those with negative cfBRAFV600E (47.1% ± 7.6% vs. 78.4% ± 5.1%, P < 0.0001; 44.6% vs. 19.0%, P = 0.001, respectively). However, no significant difference was found in the 3-year PFS rate or progression/reactivation rate between patients with positive and negative ltBRAFV600E (P = 0.348 and 0.596, respectively). In addition, after patients were divided into group A (both cfBRAFV600E and ltBRAFV600E positive, n = 56), group B (ltBRAFV600E positive and cfBRAFV600E negative, n = 28), and group C (both cfBRAFV600E and ltBRAFV600E negative, n = 56), there was a significant difference in the 3-year PFS rate and progression/reactivation rate among the three groups (47.1% ± 7.6%, 92.9% ± 6.1%, and 72.2% ± 6.1%, P < 0.001; 44.6%, 3.6%, and 26.8%, P < 0.001, respectively). In the multivariate analysis, cfBRAFV600E and age at diagnosis remained independent prognostic factors for 3-year PFS in childhood LCH. Therefore, cfBRAFV600E was more closely associated with important clinical characteristics, treatment response at week 6, and prognosis than ltBRAFV600E.

20.
Drug Des Devel Ther ; 15: 743-752, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33654380

RESUMO

Objective: This study aimed to evaluate the effectiveness of Ruxolitinib for acute/chronic graft-versus-host disease in children. Methods: This study was a retrospective trial. We analyzed the clinical characteristics of children who responded poorly to previous treatment for graft-versus-host disease (GVHD) and received ruxolitinib treatment after allogeneic hematopoietic stem cell transplantation (allo-HSCT) as an additional or replacement therapy. Results: A total of 53 patients were analyzed: aGVHD and cGVHD. The overall response rate (ORR) to ruxolitinib was 75.5%. The ORR was 64.7% (11/17) in the aGVHD group including 6, 5, and 6 patients with partial responses (PRs), complete responses (CRs), and treatment failure, respectively. The ORR was 80.6% (29/36) in the cGVHD group including 10 with CRs and 19 with PRs. Five and 2 patients showed no response and treatment failure, respectively. Four and 14 patients were GVHD recurrence in aGVHD and cGVHD respectively. A total of 14 patients (39%) discontinued steroids and 8 patients (22.2%) reduced steroids. The incidence of obvious adverse events was 94.1% (16/17) in the aGVHD group, which was higher than that in the cGVHD group. Meanwhile, the prognosis of children with cGVHD was superior to that of children with aGVHD after treatment with ruxolitinib. During the ruxolitinib treatment, only 1 patient suffered a relapse of the primary tumor. Eleven patients also suffered transplantation-associated thrombotic microangiopathy (TA-TMA) after allo-HSCT. Conclusion: Pediatric patients with GVHD (especially cGVHD) responded well to ruxolitinib treatment. Ruxolitinib can also be used as an alternative treatment for patients with TMA.


Assuntos
Doença Enxerto-Hospedeiro/terapia , Pirazóis/uso terapêutico , Administração Oral , Adolescente , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Masculino , Estrutura Molecular , Pirazóis/administração & dosagem , Estudos Retrospectivos , Relação Estrutura-Atividade , Transplante Homólogo
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