Identification of neurological complications in childhood influenza: a random forest model.

BACKGROUND: Among the neurological complications of influenza in children, the most severe is acute necrotizing encephalopathy (ANE), with a high mortality rate and neurological sequelae. ANE is characterized by rapid progression to death within 1-2 days from onset. However, the knowledge about the early diagnosis of ANE is limited, which is often misdiagnosed as simple seizures/convulsions or mild acute influenza-associated encephalopathy (IAE). OBJECTIVE: To develop and validate an early prediction model to discriminate the ANE from two common neurological complications, seizures/convulsions and mild IAE in children with influenza. METHODS: This retrospective case-control study included patients with ANE (median age 3.8 (2.3,5.4) years), seizures/convulsions alone (median age 2.6 (1.7,4.3) years), or mild IAE (median age 2.8 (1.5,6.1) years) at a tertiary pediatric medical center in China between November 2012 to January 2020. The random forest algorithm was used to screen the characteristics and construct a prediction model. RESULTS: Of the 433 patients, 278 (64.2%) had seizures/convulsions alone, 106 (24.5%) had mild IAE, and 49 (11.3%) had ANE. The discrimination performance of the model was satisfactory, with an accuracy above 0.80 from both model development (84.2%) and internal validation (88.2%). Seizures/convulsions were less likely to be wrongly classified (3.7%, 2/54), but mild IAE (22.7%, 5/22) was prone to be misdiagnosed as seizures/convulsions, and a small proportion (4.5%, 1/22) of them was prone to be misdiagnosed as ANE. Of the children with ANE, 22.2% (2/9) were misdiagnosed as mild IAE, and none were misdiagnosed as seizures/convulsions. CONCLUSION: This model can distinguish the ANE from seizures/convulsions with high accuracy and from mild IAE close to 80% accuracy, providing valuable information for the early management of children with influenza.

Influenza-Associated Encephalopathy and Acute Necrotizing Encephalopathy in Children: A Retrospective Single-Center Study.

BACKGROUND Although influenza primarily affects the respiratory system, it can cause severe neurological complications, especially in younger children, but knowledge about the early indicators of acute necrotizing encephalopathy (ANE) is limited. The main purpose of this article is to summarize the clinical characteristics, diagnosis, and treatment of neurological complications of influenza in children, and to identify factors associated with ANE. MATERIAL AND METHODS This was a retrospective study of children with confirmed influenza with neurological complications treated between 01/2014 and 12/2019 at Guangzhou Women and Children's Medical Center. A receiver operating characteristics curve analysis was performed to determine the prognostic value of selected variables. RESULTS Sixty-three children with IAE (n=33) and ANE (n=30) were included. Compared with the IAE group, the ANE group showed higher proportions of fever and acute disturbance of consciousness, higher alanine aminotransferase, higher aspartate aminotransferase, higher creatinine kinase, higher procalcitonin, higher cerebrospinal fluid (CSF) protein, and lower CSF white blood cells (all P<0.05). The areas under the curve (AUCs) for procalcitonin and CSF proteins, used to differentiate IAE and ANE, were 0.790 and 0.736, respectively. The sensitivity and specificity of PCT >4.25 ng/ml to predict ANE were 73.3% and 100.0%, respectively. The sensitivity and specificity of CSF protein >0.48 g/L to predict ANE were 76.7% and 69.7%, respectively. Thirteen (43.3%) children with ANE and none with IAE died (P<0.0001). CONCLUSIONS High levels of CSF protein and serum procalcitonin might be used as early indicators for ANE. All children admitted with neurological findings, especially during the influenza season, should be evaluated for influenza-related neurological complications.

Characteristics of Nosocomial Infections in Children Screened for SARS-CoV-2 Infection in China.

BACKGROUND This study summarizes the characteristics of children screened for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and reports the case of 1 child who was diagnosed with SARS-CoV-2 infection in Guangzhou Women and Children's Medical Center and the cases of his family members. MATERIAL AND METHODS The medical records of 159 children who were admitted to our hospital from January 23 to March 20, 2020, were retrospectively analyzed. Samples from pharyngeal or/and anal swabs were subjected to reverse-transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 within 12 h of patient admission; a second RT-PCR test was done 24 h after the first test. RESULTS Of the 159 patients, 151 patients had epidemiological histories, 14 patients had cluster onset, and 8 patients had no epidemiological history but had symptoms similar to coronavirus disease 2019 (COVID-19). The most common symptom was fever (n=125), followed by respiratory and gastrointestinal symptoms. A 7-year-old boy in a cluster family from Wuhan was confirmed with asymptomatic SARS-CoV-2 infection with ground-glass opacity shadows on his lung computed tomography scan, and his swab RT-PCR test had not turned negative until day 19 of his hospitalization. In patients who did not test positive for SARS-CoV-2, influenza, respiratory syncytial virus, and adenovirus were observed. A total of 158 patients recovered, were discharged, and experienced no abnormalities during follow-up. CONCLUSIONS For SARS-CoV-2 nosocomial infections, taking a "standard prevention & contact isolation & droplet isolation & air isolation" strategy can prevent infection effectively. Children with clustered disease need close monitoring.

Enterovirus 71 VP1 promotes mouse Schwann cell autophagy via ER stress­mediated PMP22 upregulation.

Enterovirus 71 (EV71) accounts for the majority of hand, foot and mouth disease­related deaths due to fatal neurological complications. EV71 structural viral protein 1 (VP1) promotes viral replication by inducing autophagy in neuron cells, but the effect of VP1 on myelin cells is unclear. The present study aimed to investigate the role and mechanism of VP1 in autophagy of mouse Schwann cells. An EV71 VP1­expressing vector (pEGFP­C3­VP1) was generated and transfected into mouse Schwann cells. Transmission electron microscopy and western blot analysis for microtubule­associated protein 1 light chain 3 α (LC3) II (an autophagy marker) were used to assess autophagy. Reverse transcription­quantitative PCR and immunofluorescence were performed to determine the expression of peripheral myelin protein 22 (PMP22). Small interfering RNA against PMP22 was used to investigate the role of PMP22 in mouse Schwann cell autophagy. Salubrinal [a selective endoplasmic reticulum (ER) stress inhibitor] was used to determine whether PMP22 expression was affected by ER stress. The present results indicated that VP1 promoted mouse Schwann cell autophagy. Overexpression of VP1 upregulated PMP22. PMP22 deficiency downregulated LC3II and thus inhibited autophagy. Furthermore, PMP22 expression was significantly suppressed by salubrinal. In conclusion, VP1 promoted mouse Schwann cell autophagy through upregulation of ER stress­mediated PMP22 expression. Therefore, the VP1/ER stress/PMP22 autophagy axis may be a potential therapeutic target for EV71 infection­induced fatal neuronal damage.

[Risk factors for death in children with septic shock].

OBJECTIVE: To identify the risk factors for death in children with septic shock. METHODS: Clinical data of 53 children with septic shock admitted to the Yuying Children's Hospital between January 2006 and July 2008 were retrospectively studied. Risk factors for death were assessed using univariate analysis and logistic regression analysis. RESULTS: Nineteen cases died out of 53 children with septic shock. Univariate analysis and logistic regression analysis showed that arterial blood pH value<7.0 (OR=89.66), hypotension (OR=84.00), the pediatric critical illness score<70 (OR=60.00), the number of organ dysfunction>or=3 (OR=38.98), incompletion of volume resuscitation within 6 hrs after shock (OR=26.41), and no administration of effective antibiotics within 1 hr after shock (OR=11.43) and of vasoactive drugs (OR=75.68) were risk factors for death in children with septic shock. CONCLUSIONS: A low arterial blood pH value (<7.0), hypotension, a pediatric critical illness score (<70) and the number of organ dysfunction>or=3 are related to a high mortality in children with septic shock. If the volume resuscitation can be completed within 6 hrs after shock, effective antibiotics can be administered within 1 hr after shock, and vasoactive drugs can be used properly, the outcome of children with septic shock may be improved.

[Three cases of enterovirus 71 infection with pulmonary edema or pulmonary hemorrhage as the early clinical manifestation].

OBJECTIVE: To recognize the clinical features of the enterovirus 71 (EV71) infection with pulmonary edema or pulmonary hemorrhage as a fulminant and often fatal illness. METHODS: We retrospectively reviewed the medical records of the three cases with EV71 infection for clinical manifestation, laboratory data, medications, outcome etc. RESULTS: All the cases were infants and they all died. These infants had no skin or mucosal lesions, however, they had sudden onset of cyanosis and tachypnea 1 to 2 days after the onset of the febrile disease with vomiting. All these 3 cases were misdiagnosed and were treated for shock on admission. Pulmonary hemorrhage was not considered in any of the cases on admission. All the cases received tracheal intubation when foamy secretions were discharged from mouth and nose of the patients and notable cyanosis was noted. After intubation, all had pink foamy fluid flew out from the endotracheal tube. The patients had hyperglycemia and limb weakness, two had tachycardia, and hypertension was found in one case. Chest X-ray showed bilateral or unilateral widespread air space opacity, but the cardiac size and shape were normal. All the patients had leucocytosis. EV71 infection was confirmed by detection of specific sequences of the virus in throat swab and tracheal secretions samples and in one case in cerebrospinal fluid sample. CONCLUSION: Pulmonary edema or pulmonary hemorrhage occurred in the 3 cases with EV71-infected infants. The initial presentation was often nonspecific with fever and vomiting, and sudden appearances of cyanosis, tachypnea, tachycardia, hypertension or hypotension, limb weakness may suggest pulmonary edema or hemorrhage. Excessive fluid resuscitation may deteriorate the illness, on the contrary, fluid restriction and inotropic agents, and early intubation with positive pressure mechanical ventilation may be the proper treatment.