[Role of Pediatric Critical Illness Score in evaluating severity and prognosis of severe hand-foot-mouth disease].

OBJECTIVE: To investigate the role of Pediatric Critical Illness Score (PCIS) in evaluating the prognosis and severity of severe hand-foot-mouth disease (HFMD). METHODS: This study included 424 children with severe HFMD, consisting of 390 survivors and 34 deceased patients. Related physiological parameters and clinical data were collected for calculating PCIS scores. The area under receiver operating characteristic curve (AUC) was employed to assess the performance of PCIS in evaluating the complications and outcomes. RESULTS: The median of PCIS scores for survivors was higher than that for deceased patients (P<0.01). Of the 424 children with severe HFMD, only 26 (6.1%) had critical illness according to the severity assessment using PCIS. The AUC (95%CI) of PCIS was 0.74 (0.66, 0.82) in predicting pulmonary edema, 0.82 (0.74, 0.90) in predicting pulmonary hemorrhage, and 0.83 (0.75, 0.92) in predicting death. CONCLUSIONS: PCIS can predict the complications and prognosis in children with severe HFMD. However, the existing scoring system of PCIS cannot fully assess the severity of HFMD.

The Clinical and Epidemiological Study of Children with Hand, Foot, and Mouth Disease in Hunan, China from 2013 to 2017.

Hand, foot, and mouth disease (HFMD) is endemic in the Pacific region, especially in mainland China. The case-fatality ratio of HFMD is increasing steadily. Knowledge of the changing epidemiology of HFMD in different regions is necessary for implementing appropriate intervention strategies. In this study, we describe the clinical and epidemiological characteristics of HFMD in Hunan Children's Hospital between 2013 and 2017. A total of 7203 patients with HFMD were admitted, with complication and mortality rates of 35.62% and 0.78%, respectively. The total number of children with HFMD, proportion of severely ill children, and HFMD mortality rate were the highest in 2014. The number of cases caused by EV-A71 and CV-A16 decreased continuously, while the number of cases caused by 'other enteroviruses' increased yearly since 2014, suggesting that other enteric viruses will gradually replace EV-A71 and CV-A16 as the main pathogenic HFMD agents. Furthermore, EV-A71 and mixed infections accounted for the high case fatality rates in children with severe HFMD, among whom EV-A71 infection resulted in the highest complication and mortality rates; the mild form of the disease was dominated by 'other enteroviruses'. In conclusion, the changing etiological pattern highlights the need to improve pathogen surveillance and vaccine strategies for HFMD control.

Establishment of normal reference values of NT-proBNP and its application in diagnosing acute heart failure in children with severe hand foot and mouth disease [corrected].

Hand, foot, and mouth disease (HFMD), caused by enteroviruses, is an acute contagious disease in children. Some severe infections caused by human enterovirus 71 (HEV71) lead to rapid death in children with acute heart failure (HF). N-terminal probrain natriuretic peptide (NT-proBNP) is an important indicator of HF; however, its normal reference values in children and role in HFMD remain unclear.This study aimed to investigate the correlation between NT-proBNP and heart function and establish normal reference values of NT-proBNP in children with HFMD aged 0 to 18 years.In this study, 95% normal reference values were established in 1031 healthy children aged 0 to 18 years. The correlation between NT-proBNP and left ventricular ejection (LVEF) was analyzed in 392 children with HFMD using Spearman correlation and receiver operating characteristic analysis.NT-proBNP levels were negatively correlated with LVEF in 392 children with HFMD. The median NT-proBNP level was 921 pg/mL in the early cardiorespiratory failure group, but only 55 pg/mL in the nervous system involvement group. Serum NT-proBNP levels were negatively correlated with age. The normal reference value in the neonatal period (0 to <1 month) and adolescence (13-18 years) was 250.0 to 3987.0 pg/mL and 20.0 to 145.0 pg/mL, respectively.NT-proBNP levels can reflect the severity of HFMD and discriminate the second stage from the third stage of HFMD effectively. NT-proBNP is a useful biomarker to predict the early stage of severe HFMD in children with HF. Different ages fit with different normal reference values of NT-proBNP in children.

N-terminal pro-B-type natriuretic peptide for the prognostic prediction of severe enterovirus 71-associated hand, foot, and mouth disease.

OBJECTIVE: The aim of this study was to determine whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) can predict impending brainstem encephalitis, pulmonary edema, pulmonary hemorrhage, cardiopulmonary failure, and death in children with severe enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD). METHODS: Plasma NT-proBNP levels of 282 children with severe EV71-associated HFMD were measured. RESULTS: NT-proBNP levels were significantly higher in patients with elevated blood glucose (>7.8 mmol/l) and increased white blood cell counts (>14×109/l). HFMD patients who had no complications had significantly lower NT-proBNP values than patients who died or had complications (p<0.05). The area under the receiver operating characteristic (ROC) curve was 0.73, 0.87, 0.91, 0.93, and 0.92 to discriminate between patients with and without brainstem encephalitis, pulmonary edema, pulmonary hemorrhage, circulatory failure, and death, respectively, using NT-proBNP. An NT-proBNP cut-off value of ≥1300pg/ml demonstrated a high sensitivity (85.00%) and specificity (93.51%) for predicting death in critical HFMD patients. Children with severe EV71-associated HFMD and NT-proBNP measurements ≥1300pg/ml had significantly worse overall survival compared to those with levels <1300pg/ml (p<0.05). CONCLUSIONS: NT-proBNP levels may be able to predict complications and mortality in children with severe EV71-associated HFMD disease in the intensive care unit. Serum NT-proBNP values ≥1300pg/ml on admission could be indicative of circulatory failure and increased mortality.

Derivation and Validation of a Mortality Risk Score for Severe Hand, Foot and Mouth Disease in China.

Outbreaks of hand, foot and mouth disease (HFMD) have increased recently, as has the case fatality rate in severe cases. No scoring system currently exists to predict mortality risk for severe HFMD in previous study. We retrospectively collected laboratory parameters for 546 patients with severe HFMD (a derivation and a validation cohort) at Hunan Children's Hospitals between January 2012 and December 2014. We developed a mortality risk score comprising four laboratory parameters: blood glucose (GLU), white blood cells (WBC), lactate (LAC), and N-terminal-probrain natriuretic peptide (NT-proBNP). Using an "optimal" cutoff score of 4, the sensitivity, specificity, positive predictive value and negative predictive value was 88.00%, 96.14%, 62.86% and 99.08%, respectively, in the derivation cohort. Among severe HFMD patients with low- and high-risk scores in the validation cohort, case fatality rates were 1.49% and 74.07%, respectively. According to the "optimal" cut-off in the derivation cohort, the sensitivity, specificity, positive predictive value, and negative predictive value were 80.95%, 93.83%, 62.96% and 97.44%, respectively, in the derivation cohort. The mortality risk score demonstrated good discrimination (AUC > 0.9) and calibration (P > 0.05) in both cohorts. The mortality risk score, comprising WBC, GLU, LAC and NT-proBNP, has been demonstrated good discrimination and calibration in the both cohorts.

Prognostic Value of B-Type Natriuretic Peptide, Leukocytosis, and Hyperglycemia in Children with Severe Hand, Foot, and Mouth Disease.

OBJECTIVE: Our goal is to determine the prognostic value of serum N-terminal prohormone of brain natriuretic peptide (NT-proBNP), leukocytosis, and hyperglycemia in patients with severe hand, foot, and mouth disease (HFMD). DESIGN: This is a prospective cohort study conducted from March 2011 through October 2012 at Hunan Children's Hospital. SETTING: Hunan Children's Hospital, a large children's teaching hospital with 1,500-beds located in the Changsha region of Hunan Province in China. PATIENTS: 295 children who were presented with clinical manifestation of severe HFMD, and required hospitalization. INTERVENTIONS: Standard supportive treatment for HFMD as recommended by the national guidelines. MEASUREMENTS: Admission blood samples were analyzed for NT-proBNP, leukocyte count, and serum glucose. Independent prognostic value of NT-proBNP for predicting mortality was evaluated using the Cox proportional hazard model adjusting for various covariates. MAIN RESULTS: Area under the curve of receiver operating characteristic (AUROC) analysis suggested that a serum concentration of NT-proBNP concentration more than 1,500 pg/mL is an optimal cutoff point. Twenty-four patients (8.1%) had an NT-proBNP more than 1,500 pg/mL, and a 3-day mortality of 46% (11/24). Adjusted for tachycardia, tachypnea, hypertension, hyperglycemia, leukocytosis, and conscious disturbance on presentation, elevated NT-proBNP was associated with a 22.5-fold (95% confidence interval, 3.56-142.66) increased risk of 3-day mortality. We have further improved the specificity and AUROC values by the HFMD laboratory score, which combines NT-proBNP, leukocytosis, and hyperglycemia. CONCLUSIONS: Routine admission surveillance for NT-proBNP is useful for identifying patients with HFMD at risk for mortality. Further studies are needed to determine whether early intervention in patients with highly elevated NT-proBNP can improve outcome.

Neurological complications and risk factors of cardiopulmonary failure of EV-A71-related hand, foot and mouth disease.

From 2010 to 2012, large outbreaks of EV-A71-related- hand foot and mouth disease (HFMD) occurred annually in China. Some cases had neurological complications and were closely associated with fatal cardiopulmonary collapse, but not all children with central nervous system (CNS) involvement demonstrated a poor prognosis. To identify which patients and which neurological complications are more likely to progress to cardiopulmonary failure, we retrospectively studied 1,125 paediatric inpatients diagnosed with EV-A71-related HFMD in Hunan province, including 1,017 cases with CNS involvement. These patients were divided into cardiopulmonary failure (976 people) group and group without cardiopulmonary failure (149 people). A logistic regression analysis was used to compare the clinical symptoms, laboratory test results, and neurological complications between these two groups. The most significant risk factors included young age, fever duration ≥3 days, coma, limb weakness, drowsiness and ANS involvement. Patients with brainstem encephalitis and more CNS-involved regions were more likely to progress to cardiopulmonary failure. These findings can help front-line clinicians rapidly and accurately determine patient prognosis, thus rationally distributing the limited medical resources and implementing interventions as early as possible.