Clinical Features and Prognostic Factors of Early Outcome in Pediatric Hemophagocytic Lymphohistiocytosis: A Retrospective Analysis of 227 Cases.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening clinical syndrome in children, and the knowledge of it is still limited. Two hundred twenty-seven children with HLH in our hospital were retrospectively analyzed from January 2001 to December 2018. The age of the patients on admission ranged from 1 day to 14 years old. The 3 most common clinical manifestations include fever (98.7%), hepatomegaly (95.6%), and splenomegaly (92.1%). The decrease of high-density lipoprotein cholesterol (99.1%) is very common in children with HLH. Albumin<25 g/L, activated partial thromboplastin time >65 s, and lactose dehydrogenase >1000 U/L were independent risk factors for poor early prognosis in children with HLH, and their odds ratio values were 2.515, 3.094, and 2.378, respectively, while age >28 months was identified as a protective factor (odds ratio=0.295). Of the 227 children, 67 (29.52%) died within 30 days of onset. The mortality rate in 2013 to 2018 was significantly lower than that in 2001 to 2012 (16.35% vs. 40.65%, P=0.000). The shortening of the time from onset to admission and the reduction of time from admission to definite diagnosis could be some of the reasons for the decrease of HLH mortality in 2013 to 2018 (P<0.05, respectively). Our study suggests that early identification of risk factors for HLH, timely diagnosis and treatment are important measures to improve the short-term prognosis of HLH in children.

Tratamiento satisfactorio con fluconazol de la candidemia relacionada con el catéter porCandida haemulonii: informe sobre dos pacientes neonatales / Successful fluconazole treatment of catheter-related candidemia caused by Candida haemulonii: report of 2 neonatal cases

La Candida haemulonii forma parte de la especie Candida no albicans. La candidemia por C. haemulonii es sumamente infrecuente, pero mortal, en los recién nacidos. Se informa sobre los dos primeros recién nacidos con candidemia por C. haemulonii en China tratados con fluconazol y se revisan dos artículos informados con anterioridad. Nuestro informe incrementa la sensibilización sobre la candidemia por C. haemulonii en recién nacidos críticos y resalta la importancia de un diagnóstico y un tratamiento tempranos de esta infección mortal.

Candida haemulonii forms part of the non-albicans Candida species. The candidemia caused by C. haemulonii is extremely rare but fatal in neonates. We reported the first two neonates with C. haemulonii candidemia in China which were treated with fluconazole and reviewed two papers previously reported. Our report adds further awareness on C. haemulonii candidemia in critical neonates and points out the importance of an early diagnosis and treatment of this fatal infection.

Management of Refractory Orofacial Dyskinesia Caused by Anti-N-methyl-d-aspartate Receptor Encephalitis Using Botulinum Toxin.

The use of botulinum neurotoxin serotype A (BoNT-A) injections for the treatment of orofacial dyskinesia secondary to anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is rarely reported. Here, we report a case of an urgent, successful management of severe orofacial dyskinesia in an 8-year-old girl with anti-NMDAR encephalitis using BoNT-A injection. The patient presented with de novo unilateral paroxysmal movement disorder progressing to generalized dystonia and repetitive orofacial dyskinesia. Diagnosis was confirmed by the presence of NMDAR antibodies in serum and cerebrospinal fluid. The orofacial dyskinesia worsened despite the aggressive use of first-line immunotherapy and second-line immunotherapy (rituximab), and resulted in a potentially fatal self-inflicted oral injury. We urgently attempted symptomatic management using BoNT-A injections in the masseter, and induced muscle paralysis using vecuronium. The patient's severe orofacial dyskinesia was controlled. We observed the effects of the BoNT-A injections and a tapering off of the effects of vecuronium 10 days after the treatment. The movement disorder had improved significantly 4 weeks after the first administration of rituximab. The injection of BoNT-A into the masseter may be an effective treatment for medically refractory orofacial dyskinesia in pediatric patients with anti-NMDAR encephalitis. We propose that the use of BoNT-A injections should be considered early to avoid self-inflicted oral injury due to severe refractory orofacial dyskinesia in patients with anti-NMDAR encephalitis.

Activating adenosine A1 receptor accelerates PC12 cell injury via ADORA1/PKC/KATP pathway after intermittent hypoxia exposure.

Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with the neurocognitive deficits as a result of the neuronal cell injury. Previous studies have shown that adenosine A1 receptor (ADORA1) played an important role against hypoxia exposure, such as controlling the metabolic recovery in rat hippocampal slices and increasing the resistance in the combined effects of hypoxia and hypercapnia. However, little is known about whether ADORA1 takes part in the course of neuronal cell injury after intermittent hypoxia exposure which was the main pathological characteristic of OSAHS. The present study is performed to explore the underlying mechanism of neuronal cell injury which was induced by intermittent hypoxia exposure in PC12 cells. In our research, we find that the stimulation of the ADORA1 by CCPA accelerated the injury of PC12 cells as well as upregulated the expression of PKC, inwardly rectifying potassium channel 6.2(Kir6.2) and sulfonylurea receptor 1(SUR1) while inhibition of the ADORA1 by DPCPX alleviated the injury of PC12 cells as well as downregulated the expression of PKC, Kir6.2, and SUR1. Moreover, inhibition of the PKC by CHE, also mitigated the injury of PC12 cells, suppressed the Kir6.2 and SUR1 expressions induced by PKC. Taken together, our findings indicate that ADORA1 accelerated PC12 cells injury after intermittent hypoxia exposure via ADORA1/PKC/KATP signaling pathway.

Chronic intermittent hypoxia exposure induces kidney injury in growing rats.

OBJECTIVE: The objectives of this paper are to examine the effect of chronic intermittent hypoxia (CIH) on the morphological changes in the kidney of growing rats and to explore the mechanisms underlying the CIH-induced renal damage. METHODS: Forty Sprague-Dawley rats were randomly divided into two groups: 2 and 4 weeks CIH groups (2IH, 4IH), and in the control group 2 and 4 weeks air-stimulated groups (2C, 4C), with 10 rats in each group. Pathological changes of renal tissue were observed by HE staining, PAS staining, and Masson staining. Real-time PCR method was used to detect the mRNA expression of HIF-1α, CuZnSOD/ZnSOD, and MnSOD in renal tissue. RESULTS: (1) Intermittent hypoxia (IH) caused morphological damage in the kidney. Hypertrophy of epithelial cells in the kidney tubules and dilation in the glomeruli were observed under light microscope in HE and PAS stain, especially in 4IH group. Masson staining showed no significant fibrotic response in the IH groups. (2) Compared with the corresponding control groups, the levels of serum SOD were significantly lower in CIH groups, and especially in 4IH group. The mRNA expression of Cu/ZnSOD and MnSOD in CIH groups decreased significantly as compared to control groups. The mRNA levels of HIF-1α in the kidney were significantly higher in CIH groups than those in the corresponding control groups. CONCLUSION: Oxidative stress played a critical role in renal damage by up-regulating HIF-1α transcription and down-regulating Cu/ZnSOD and MnSOD transcription after chronic intermittent hypoxia exposure in growing rats.

Lamotrigine monotherapy for paroxysmal kinesigenic dyskinesia in children.

PURPOSE: To evaluate the efficacy and tolerability of lamotrigine monotherapy in children with paroxysmal kinesigenic dyskinesia. METHOD: A sample of eighteen children aged between 2 years old and 13 years old who fulfilled the diagnostic criteria from January 2008 to December 2014 was enrolled, they received video electroencephalography, brain image scans and proline-rich transmembrane protein 2 genetic tests. Children with known or suspected diseases which would cause secondary paroxysmal kinesigenic dyskinesia were excluded. The initial dosage of lamotrigine was 6.25 mg, and it was gradually increased every week until attacks were controlled. Patients entered the maintenance dose phase upon reaching the effective dosage, and by being attack free at two consecutive outpatient visits. They were followed up for a couple of years until December 2014. RESULTS: By the end of the 4th week, the attack-free rate reached 100% among all the patients. During the maintenance dose phase, 16 patients remained attack free, 2 patients received additional drug due to attack relapses when they entered puberty. Three patients had relapses because of non-compliance to the therapy, but they became attack free as soon as they re-started the medicine. The mean daily dosage was 26.4 mg (range 6.25-50). Definite adverse effect related to the drug was not reported in follow up. CONCLUSION: LTG monotherapy is effective and well tolerated for PKD in children.