[Analysis of risk factors of mortality in infants and toddlers with moderate to severe pediatric acute respiratory distress syndrome].

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ2=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ2=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ2=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.

[Effect and influence factors of cardiopulmonary resuscitation in children with congenital heart disease in pediatric intensive care unit].

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ2=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ2=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.

Aetiology of tinea capitis in China: a multicentre prospective study.

BACKGROUND: Tinea capitis is still common in developing countries, such as China. Its pathogen spectrum varies across regions and changes over time. OBJECTIVES: This study aimed to clarify the current epidemiological characteristics and pathogen spectrum of tinea capitis in China. METHODS: A multicentre, prospective descriptive study involving 29 tertiary hospitals in China was conducted. From August 2019 to July 2020, 611 patients with tinea capitis were enrolled. Data concerning demography, risk factors and fungal tests were collected. When necessary, the pathogens were further identified by morphology or molecular sequencing in the central laboratory. RESULTS: Among all enrolled patients, 74·1% of the cases were in patients aged 2-8 years. The children with tinea capitis were mainly boys (56·2%) and were more likely than adults to have a history of animal contact (57·4% vs. 35·3%, P = 0·012) and zoophilic dermatophyte infection (73·5% vs. 47%). The adults were mainly female (83%) and were more likely than children to have anthropophilic agent infection (53% vs. 23·9%). The most common pathogen was zoophilic Microsporum canis (354, 65·2%), followed by anthropophilic Trichophyton violaceum (74, 13·6%). In contrast to the eastern, western and northeastern regions, where zoophilic M. canis predominated, anthropophilic T. violaceum predominated in central China (69%, P < 0·001), where the patients had the most tinea at other sites (20%) and dermatophytosis contact (26%) but the least animal contact (39%). Microsporum ferrugineum was the most common anthropophilic agent in the western area, especially in Xinjiang province. CONCLUSIONS: Boys aged approximately 5 years were the most commonly affected group. Dermatologists are advised to pay more attention to the different transmission routes and pathogen spectra in different age groups from different regions.

[Effectiveness of ketamine in the treatment of refractory and super-refractory status epilepticus in children].

Objective: To investigate the effectiveness of ketamine in the treatment of refractory status epilepticus (RSE) and super refractory status epilepticus (SRSE) in children. Methods: A retrospective study was conducted to collect and analyze the medical data of 18 children with RSE or SRSE who received ketamine in intensive care unit of Beijing Children's Hospital from January 2016 to December 2018. According to the different regimen of ketamine, all children were divided into the loading-maintenance group (7 cases) and the maintenance group (11 cases). According to the control of status epilepticus, the patients were divided into controlled group (11 cases) and non-responsive group (7 cases).Wilcoxon's rank sum test or Fisher's exact test were used to compare the effectiveness between groups. Results: There were 9 males and 9 females in the study group, aged 6.7 (4.5, 9.0) years. Seven cases had RSE and the remaining had SRSE. Four cases died during hospitalization. After the initiation of ketamine treatment, RSE and SRSE were controlled in 11 children. The duration of ketamine administration was 4 (2, 11) days. The dose was 2.2 (1.2, 5.3) mg/(kg·h) in all patients, and 2.4 (1.3, 6.0) mg/(kg·h), 2.0 (1.0, 4.0) mg/(kg · h) in the controlled and non-responsive group, respectively (Z=-0.272, P=0.791). The RSE or SRSE were terminated in all the 7 patients who received loading dose of ketamine, with the dose of 1.5 (0.3,1.6) mg/kg. In the 11 patients who only received maintenance treatment, 4 had the RSE and SRSE terminated, which showed a significantly lower effectiveness than in loading-maintenance group (7/7 vs. 4/11, P=0.01). Regarding the adverse reactions, saliva secretion increased in 8 children during the ketamine administration, otherwise unremarkable. Conclusion: Loading dose followed by maintenance of ketamine can control children's RSE and SRSE well, without significant adverse reactions.

[Effectiveness and safety of nimodipine in preventing cerebral vasospasm after subarachnoid hemorrhage in children].

Objective: To evaluate the effect of prophylactic nimodipine in vasospasm prevention and outcome improvement in children with subarachnoid hemorrhage (SAH). Methods: A prospective, randomized controlled clinical trial which enrolled children with SAH who were admitted to pediatric intensive care unit (PICU) of Beijing Children's Hospital from January 2015 to October 2018 was conducted. A total of 43 patients were randomly divided into nimodipine group (24 patients) and control group (19 patients) according to random number table. Transcranial Doppler (TCD) was used to dynamically monitor blood flow velocity and spectrum monography of bilateral middle cerebral artery (MCA) for vasospasm evaluation. Pediatric cerebral performance category (PCPC) scale was used to evaluate patients' brain function on 28(th) day after discharge. Data were analyzed by t test, Mann-Whitney U test, χ(2) test. Results: Except heart rate ((157±26) vs. (137±34) beats/min, t=2.079, P=0.045), no significant differences existed between the two groups in basic demographic characteristics, primary diseases, and clinical manifestations (all P>0.05). The peak velocities of bilateral MCA on the 5(th) day after admission were significantly lower in nimodipine group (left MCA (136±34) vs. (158±23) cm/s, t=-2.890, P=0.006; right MCA (129±34) vs. (176±27) cm/s, t=-3.717, P=0.001). Likewise, a lower peak velocity of left MCA was observed on the 7(th) day after admission in nimodipine group ((127±45) vs. (152±13) cm/s, t=-2.903, P=0.007), but no significant difference existed in that of right MCA ((131±48) vs. (150±22) cm/s, t=-1.760, P=0.090). Eleven patients suffered from vasospasm, 25% (6/24) in nimodipine group and 26% (5/19) in control group (χ(2)=0.010, P=1.000), within whom 8 patients had complete remission after continuing nimodipine treatment, one died in hospital and the other two's vasospasm still existed at the time of discharge. No significant differences were found between the two groups in mean length of hospitalization, proportion of mechanical ventilation, Glasgow coma scale at discharge, survival rate at discharge or survival rate on 28(t)h day after discharge (all P>0.05). However, nimodipine group had a higher proportion of favorable PCPC brain function (92% (22/24) vs. 63% (12/19), χ(2)=5.208, P=0.030). No side effects such as hypotension, rash or injection site erythema were observed. Conclusion: Prophylactic nimodipine cannot reduce vasospasm incidence in children with SAH but may improve short-term brain function, without any significant safety issues.

[Clinical and genetic characteristics of congenital myasthenia syndrome with episodic apnea caused by CHAT gene mutation: a report of 2 cases].

Objective: To investigate the clinical and genetic features of congenital myasthenia syndrome with episodic apnea (CMS-EA) caused by gene mutation of choline acetyltransferase (CHAT) Methods: The clinical data of 2 patients with congenital myasthenia syndrome were collected, and both were diagnosed from 2013 to 2015 in Beijing Children's Hospital, Capital Medical University. The clinical features and gene mutation characteristics were analyzed, and the patients were followed-up for therapeutic efficacy. Results: The two patients (case 1 and case 2) had the onset soon after birth and at 3 months after birth respectively. The two patients were admitted to the PICU due to dyspnea, cyanotic episodes that required intubation. The patients had repeated apnea and became ventilator dependent. Case 1 died due to refusal of any treatment. Case 2 had a tracheotomy, and gradually weaned from ventilator after using pyridostigmine. The hospitalization of case 2 lasted 162 days. Case 2 was followed up to the age of 3 years and 4 months, and was extubated and was maintained on oral neostigmine but still had fluctuating ptosis and minor physical and mental retardation. Both cases were negative for anti-AChR, anti-acetylcholinesterase, anti-MuSK antibodies. Neostigmine test was negative in case 1 and suspiciously positive in case 2. Low-frequency repetitive nerve stimulation testing of case 2 was negative. Cranial MRI scans of both cases showed brain atrophy-like change. Genetic testing showed compound heterozygous deletions (exon 4, 5, 6) and pathogenic variant c.914T>C (p.I305T) in CHAT in case 1, compound heterozygous variants c.1007T>C (p.I336T) and c.64C>T (p.Q22X) in CHAT in case 2. To our knowledge, compound heterozygous deletions (exon 4, 5, 6) and p.Q22X were novel, previously unreported variants. Conclusion: CMS-EA usually presents at birth or in the neonatal period with hypotonia, ptosis, dysphagia due to severe bulbar weakness, and respiratory insufficiency with cyanosis and apnea. Early treatment with pyridostigmine is helpful to the improvement of clinical symptoms and prognosis.

Involvement of tau phosphorylation in traumatic brain injury patients.

OBJECTIVES: Traumatic brain injury (TBI) results in significant morbidity and mortality throughout the world. In TBI patients suffering cognitive, emotional, and behavioral deficits, the leading cause derives from the physical injury to the central nervous system (CNS) that impairs brain function. MATERIALS AND METHODS: Here, we applied a targeted approach to understand the potential mechanisms of neuron damage after TBI. Tau protein phosphorylation was compared in the brain tissues collected from patients underwent brain surgery based on the assessment of brain injury extent by Glasgow Coma Scale (GCS). RESULTS: The results indicated that the levels of phosphorylated tau were significantly higher in the severe and extremely severe TBI groups, compared to the moderate group of patients. Phosphorylated, but not the total tau protein was uniquely correlated with the GCS score (R2 =.7849, P<.01) in 142 TBI patients. Consistently, the activities of key players associated with tau hyperphosphorylation GSK-3ß and PP2A showed parallel correlations with the severity of TBI as well. CONCLUSION: These data suggest that the enhanced tau protein phosphorylation occurs upon severe neuron injures and may contribute to the pathological structural changes of CNS leading to brain damage of TBI.

[Expression pattern of beta-amyloid in the peri-infarct area and ipsilateral thalamus of rats after focal cerebral cortex infarction].

Objective: To investigate the expression pattern of beta-amyloid (Aß) in rats after focal cerebral cortex infarction, and to identify whether the Aß expression in the ipsilateral thalamus was directly related to focal cerebral ischemia. Methods: The distal middle cerebral artery occlusion (MCAO) was performed by electrocoagulation in rats. The rats were divided randomly into sham group (n=18) and MCAO group (n=30) . We used 2, 3, 5-triphenyltetrazolium chloride (TTC) staining and immunohistochemical staining to detect the location of cerebral infarction and Aß expression, respectively. Results: TTC staining showed that the cerebral infarction was consistently restricted to the frontal and temporoparietal cortex. In the peri-infarct area of the MCAO group, Aß expression began at day 2, reached the maximum level at day 7, and disappeared almost completely at day 28 after MCAO. The Aß appeared as diffuse small dots, and was located in neurons and astrocytes at day 2 and day 28, respectively. Meanwhile, in the ipsilateral thalamus, Aß expression began at day 3, increased markedly at day 7, and remained until day 28 after MCAO. The Aß was located constantly in the extracellular region of the ipsilateral thalamus, and aggregated gradually from small dots to dense plaque-like deposits with the time of ischemia. Conclusions: There are dynamic changes of Aß expression in both the peri-infarct area and the ipsilateral thalamus following MCAO. The Aß expression in the ipsilateral thalamus is not directly related to focal cerebral ischemia.

[The clinical and imaging features of 118 patients with spontaneous cerebral arterial dissections presenting with ischemic stroke].

OBJECTIVE: To investigate the clinical and radiologic features of patients with spontaneous cerebral arterial dissections (CADs) presenting with ischemic stroke and to explore the effect of gender and age on those features. METHODS: Patients admitted to our stroke center diagnosed as ischemic stroke secondary to CADs from August 2008 to April 2015 were prospectively registered. Patients aged between 15 to 80 years old, who had acute brain infarcts within the territory of a major cerebral artery affected by a dissection confirmed by the neuroradiological examinations, were enrolled in the study. The followings were the exclusion criteria: (1) there were any potential causes for the brain infarcts other than CADs; (2) CADs were the results of a definite cause; (3) the clinical data were incomplete. RESULTS: A total of 118 patients were enrolled in the study with the mean age of (44.2±12.8) years old. There were 87 men (73.7%) and 67 patients (56.8%) aged under 45 years old. Smoking (41.5%), hypertension (25.4%) and hypercholesterolemia (21.2%) were the three leading risk factors for stroke. Hypercholesterolemia was more common in the male patients (25.3% vs 9.7%, P=0.021), whereas hypertension (39.2% vs 14.9%, P=0.005) and diabetes (25.5% vs 4.5%, P=0.002) were more common in the patients aged 45 years or older. Headache or neck pain before or at the onset of stroke was more common in the female patients (67.7% vs 34.5%, P=0.002). A total of 71 patients were found with CADs of the anterior circulation, while 47 patients with that of the posterior circulation. The involvement of the intra and extracranial arteries were documented in 59 and 59 patients, respectively. The middle cerebral artery (MCA) was the most common site in the intracranial dissection and more MCA dissections were observed in the male patients (46.3% vs 11.1%, P=0.016). The dissection of intracranial carotid artery was more common in patients aged under 45 years old (38.7% vs 0, P<0.001). Lumen status of CADs often presented as stenosis (43.2%) and occlusion (41.2%), while less aneurysm (5.9%) and aneurysm with stenosis (9.3%) were observed. Aneurysm was found to be more common in patients aged 45 years or older (11.8% vs 1.5%, P=0.042). CONCLUSION: Chinese patients with spontaneous CADs presenting with ischemic stroke have unique clinical and imaging features, which correlated with age and gender.

Rituximab regulates the expression of the Raf kinase inhibitor protein via NF-κB in renal tissue of rats with diabetic nephropathy.

This study aimed to investigate the expression levels of the Raf kinase inhibitor protein (RKIP) and NF-κB in renal tissues of diabetic nephropathy (DN) rats, and to determine the underlying molecular targets of rituximab (RTX), with the goal of developing new clinical treatment selection for DN. Sprague-Dawley rats were randomly divided into a normal group (N), a DN group (M), and an RTX treatment group (D). Blood glucose and 24-h urine protein levels of rats were determined. The expression levels of RKIP and NF-κB in glomerular tissues were determined by immunohistochemistry staining and Western blotting. Comparisons between the M and N groups revealed that the concentrations of blood glucose and 24-h urine protein were significantly increased by DN (P < 0.01), and the expression levels of RKIP and NF-κB were significantly decreased and increased (P < 0.05), respectively. In the D group, the expression levels of RKIP and NF-κB were, respectively, upregulated and downregulated by RTX, and the concentrations of 24-h urine protein were also decreased by RTX. These results suggest that expression levels of RKIP might be regulated by RTX via NF-κB. This pathway could play an important role in the development and pathogenesis of DN. Therefore, RTX could be selected for clinical treatment of DN.

Netrin-1 rescues neuron loss by attenuating secondary apoptosis in ipsilateral thalamic nucleus following focal cerebral infarction in hypertensive rats.

Neurological deficit following cerebral infarction correlates with not only primary injury, but also secondary neuronal apoptosis in remote loci connected to the infarction. Netrin-1 is crucial for axonal guidance by interacting with its receptors, deleted in colorectal cancer (DCC) and uncoordinated gene 5H (UNC5H). DCC and UNC5H are also dependence receptors inducing cell apoptosis when unbound by netrin-1. The present study is to investigate the role of netrin-1 and its receptors in ipsilateral ventroposterior thalamic nucleus (VPN) injury secondary to stroke in hypertensive rats. Renovascular hypertensive Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO). Continuous intracerebroventricular infusion of netrin-1 (600 ng/d for 7 days) or vehicle (IgG/Fc) was given 24h after MCAO. Neurological function was evaluated by postural reflex 8 and 14 days after MCAO. Then, immunoreactivity was determined in the ipsilateral VPN for NeuN, glial fibrillary acidic protein, netrin-1 and its receptors (DCC and UNC5H2), apoptosis was detected with Terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling (TUNEL) assay, and the expressions of caspase-3, netrin-1, DCC, and UNC5H2 were quantified by western blot analysis. MCAO resulted in the impaired postural reflex after 8 and 14 days, with decreased NeuN marked neurons and increased TUNEL-positive cells, as well as an up-regulation in the levels of cleaved caspase-3 and UNC5H2 protein in the ipsilateral VPN, without significant change in DCC or netrin-1 expression. By exogenous netrin-1 infusion, the number of neurons was increased in the ipsilateral VPN, and both TUNEL-positive cell number and caspase-3 protein level were reduced, while UNC5H2 expression remained unaffected, simultaneously, the impairment of postural reflex was improved. Taken together, the present study indicates that exogenous netrin-1 could rescue neuron loss by attenuating secondary apoptosis in the ipsilateral VPN after focal cerebral infarction, possibly via its receptor UNC5H2, suggesting that relative insufficiency of endogenous netrin-1 be an underlying mechanism of secondary injury in the VPN post stroke.

Exophiala spinifera and its allies: diagnostics from morphology to DNA barcoding.

Diagnostic features of morphology, physiology, serology and genetics of species belonging to the Exophiala spinifera clade (including 11 species: Exophiala oligosperma, E. spinifera, E. xenobiotica, E. jeanselmei, E. exophialae, E. nishimurae, E. bergeri, E. nigra, Rhinocladiella similis, Ramichloridium basitonum and Phaeoannellomyces elegans), comprising a large number of human-associated Exophiala species, are summarized. Several species have closely similar morphological characters and physiological profiles. Taxonomy is therefore primarily based on sequence diversity of the Internal Transcribed Spacer (ITS) region of ribosomal DNA (rDNA). Multilocus sequencing has shown that ITS is reliable for identification of the species in this clade, and is a therefore a good candidate for barcoding species of Exophiala. Species-specific fragments were searched in the ITS region of species in the Exophiala spinifera clade and can be used to design probes for diagnosis by hybridization.