Short-term efficacy of empagliflozin in children with glycogen storage disease type Ⅰb / 中华儿科杂志

Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×109, 0.50×109, 0.48×109, 0.48×109/L to 1.48×109, 3.04×109, 1.10×109, 0.73×109/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.

Analysis of clinical characteristics of 35 inflammasomopathies cases / 中华儿科杂志

Objective: To summarize the clinical characteristics of inflammasomopathies, enhance the recognition of those diseases, and help to establish the early diagnosis. Methods: The clinical manifestations including fever, rash, systems involvement as well as laboratory results and genotypic characteristics of 35 children with inflammasomopathies diagnosed by the Department of Pediatrics, Peking Union Medical College Hospital, from January 1, 2008 to December 31, 2020 were analyzed retrospectively. Results: A total of 35 cases of inflammasomopathies were diagnosed, and 20 of them were boys while 15 were girls. Inflammasomopathies patients have early onset, the age of onset as well as diagnostic age were 1 (0,7) and 7 (3,12), respectively. Among those patients, 10 had familial mediterranean fever, 3 had mevalonate kinase deficiency, 15 cases had NLRP3 gene associated autoinflammatory disease, 4 cases had NLRP12-associated autoinflammatory disease, 2 cases had familial cold autoinflammatory syndrome 3, and 1 case had familial cold autoinflammatory syndrome 4. A total of 34 cases (97%) showed recurrent fever, 27 cases (77%) had skin rashes, while 11 cases (31%), 10 cases (29%), and 8 cases (23%) were presented with lymphadenopathy, hepatosplenomegaly and growth retardation, respectively. In terms of systemic involvement, there were 18 cases (51%), 12 cases (34%), 8 cases (23%), and 5 cases (14%) with skeletal, neurological, auditory, and renal involvement, respectively. Central nervous system involvement was seen only in NLRP3 gene associtated autoinflammatory diseases (12 cases), sensorineural deafness was seen in NLRP3 gene associtated autoinflammatory diseases (6 cases) and NLRP12 gene associated autoinflammatory diseases (2 cases), and abdominal pain was observed in familial Mediterranean fever (5 cases), mevalonate kinase deficiency (1 case) and NLRP12 gene related autoinflammatory diseases (1 case). In the acute inflammatory phase, the acute phase reactants (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) of 35 cases (100%) were significantly increased. There were 21 cases received ferritin examination, and only 4 cases (19%) showed an increase of it. In terms of autoantibodies, among all 35 patients, 4 cases (11%) were positive for antinuclear antibodies (ANA). Conclusions: Fever, skin rash, and skeletal manifestations are the most common clinical features, accompanied with increased CRP and ESR, and negative results of autoantibodies such as ANA. The clinical manifestations of those diseases are complex and diverse, and it is prone to delayed diagnosis and treatment.

Diagnosis of two Wilson's disease patients in one pedigree and analysis of related factors of its different clinical phenotypes / 基础医学与临床

Objective To study the clinical features of Wilson's disease patients with different clinical phenotypes in one pedigree. To make the diagnosis and summarize the factors influencing the clinical manifestations of patients with Wilson's disease. Methods The clinical data of siblings in this pedigree were collected.The literature about the fac-tors influencing the clinical phenotype of Wilson's disease were found. Results There were two siblings in one pedi-gree with Wilson's disease.The younger brother whose phenotype is liver-type,was 6 years old. His brother was 16 years old and showed mixed type(nerve+kidney).Their genotype are exon5.c.1714delG(maternal),exon8.c.2333G>T,p.R778L(paternal). They have the same genotype but different phenotypes and different age of onset. After re-viewing the literature,we found some factors outside the ATP7B gene may also affect the clinical phenotype. Conclu-sions Genetic testing is of great importance in children with Wilson's disease.Screening for hepatolenticular degener-ation should be performed in children with liver disease or neurological manifestations.In addition to the ATP7B gene, the clinical phenotype of hepatolenticular degeneration may also be affected by many other factors.

Risk factors for Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae colonization in neonates / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To identify risk factors for Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) colonization in neonates hospitalized in the neonatal intensive care unit (NICU).</p><p><b>METHODS</b>A case-control study was conducted. The case group included nine patients colonized with KPC-Kp between 1 August 2012 and 31 April 2013 and the controls were selected randomly from patients without KPC-Kp colonization during the same period. Univariable analysis and multivariable logistic regression analysis were conducted to identify risk factors for KPC-Kp colonization.</p><p><b>RESULTS</b>The univariable analysis showed 11 factors associated with KPC-Kp colonization: gestational age, birth weight, length of hospital stay, duration of mechanical ventilation, congenital heart disease, peripherally inserted central catheter, surgical operation, duration of intravenous nutrition, carbapenems use, duration of carbapenems use and glycopeptides use. The multivariable logistic regression analysis showed that exposure to more than 4 days of carbapenems use (OR=18.7, 95%CI: 1.98-175.5, P=0.01) was an independent risk factor for KPC-Kp colonization. The intervention to control KPC-Kp colonization included contact isolation, active surveillance, and rational use of antibiotics.</p><p><b>CONCLUSIONS</b>Exposure to prolonged use of carbapenems is an independent risk factor for the development of KPC-Kp colonization in neonates hospitalized in the NICU.</p>

Concentrations of granulocyte colony-stimulating factor in children with moyamoya disease / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the roles of granulocyte colony-stimulating factor in the pathogenesis of moyamoya disease.</p><p><b>METHODS</b>Serum G-CSF concentrations were measured using enzyme linked immunosorbent assay (ELISA) in 20 children with moyamoya disease and 20 healthy children.</p><p><b>RESULTS</b>Serum G-CSF concentration (35.7+/-10.3 pg/mL) in children with moyamoya disease was significantly higher than that in healthy controls (23.5+/-3.8 pg/mL) (p<0.01).</p><p><b>CONCLUSIONS</b>The elevated serum G-CSF concentration in children with moyamoya disease suggests that G-CSF may play an important role in the pathogenesis of moyamoya disease.</p>