The fluid management and hemodynamic characteristics of PiCCO employed on young children with severe hand, foot, and mouth disease-a retrospective study.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is an acute infectious disease caused by human enterovirus 71 (EV71), coxsackievirus, or echovirus, which is particularly common in preschool children. Severe HFMD is prone to cause pulmonary edema before progressing to respiratory and circulatory failure; thus hemodynamic monitoring and fluid management are important to the treatment process. METHODS: We did a review of young patients who had been successfully treated in our department for severe HFMD, which had been caused by EV71. A total of 20 patients met the inclusion criteria. Eight cases were monitored by the pulse indicator continuous cardiac output (PiCCO) technique, and fluid management was administered according to its parameters. With regard to the treatment with PiCCO monitoring, patients were divided into two groups: the PiCCO group (8 patients) and the control group (12 patients). The groups were then compared comprehensively to evaluate whether PiCCO monitoring could improve patients' clinical outcomes. RESULTS: After analysis, the findings informed that although PiCCO failed to shorten the length of ICU stay, reduce the days of vasoactive drug usage, or lower the number of cases which required mechanical ventilation, PiCCO did reduce the incidence of fluid overload (p = 0.085) and shorten the days of mechanical ventilation (p = 0.028). After effective treatment, PiCCO monitoring indicated that the cardiac index (CI) increased gradually(p < 0.0001), in contrast to their pulse (P, p < 0.0001), the extra vascular lung water index (EVLWI, p < 0.0001), the global end diastolic volume index (GEDVI, p = 0.0043), and the systemic vascular resistance index (SVRI, p < 0.0001), all of which decreased gradually. CONCLUSION: Our study discovered that PiCCO hemodynamic monitoring in young children with severe HFMD has some potential benefits, such as reducing fluid overload and the duration of mechanical ventilation. However, whether it can ameliorate the severity of the disease, reduce mortality, or prevent multiple organ dysfunction remain to be further investigated.

Molecular epidemiology of enteroviruses associated with severe hand, foot and mouth disease in Shenzhen, China, 2014-2018.

In this study, we investigated the epidemiology and molecular characteristics of enteroviruses associated with severe hand, foot and mouth disease (HFMD) in Shenzhen, China, during 2014-2018. A total of 137 fecal specimens from patients with severe HFMD were collected. Enterovirus (EV) types were determined using real-time reverse transcription polymerase chain reaction (RT-PCR), RT nested PCR, and sequencing. Sequences were analyzed using bioinformatics programs. Of 137 specimens tested, 97 (70.8%), 12 (8.8%), and 10 (7.3%) were positive for EV-A71, coxsackievirus A6 (CVA6), and CVA16, respectively. Other pathogens detected included CVA2 (2.9%, 4/137), CVA10 (2.9%, 4/137), CVA5 (0.7%, 1/137), echovirus 6 (E6) (0.7%, 1/137) and E18 (0.7%, 1/137). The most frequent complication in patients with proven EV infections was myoclonic jerk, followed by aseptic encephalitis, tachypnea, and vomiting. The frequencies of vomiting and abnormal eye movements were higher in EV-A71-infected patients than that in CVA6-infected or CVA16-infected patients. Molecular phylogeny based on the complete VP1 gene revealed no association between the subgenotype of the virus and disease severity. Nevertheless, 12 significant mutations that were likely to be associated with virulence or the clinical phenotype were observed in the 5'UTR, 2Apro, 2C, 3A, 3Dpol and 3'UTR of CVA6. Eight significant mutations were observed in the 5'UTR, 2B, 3A, 3Dpol and 3'UTR of CVA16, and 10 significant mutations were observed in the 5'UTR, VP1, 3A and 3Cpro of CVA10. In conclusion, EV-A71 is still the main pathogen causing severe HFMD, although other EV types can also cause severe complications. Potential virulence or phenotype-associated sites were identified in the genomes of CVA6, CVA16, and CVA10.

The Epidemiological and Clinical Characteristics of Hand, Foot, and Mouth Disease in Hangzhou, China, 2016 to 2018.

Hand, foot, and mouth disease (HFMD) is most frequently caused by several serotypes of human enterovirus (EV) including Enterovirus 71 (EV-A71), coxsackievirus A16 (CV-A16), or other types of EV. The aim of this study was to determine the epidemiological characteristics of HFMD and to describe the epidemiologic characteristics of HFMD among severe and mild cases. We collected 4760 HFMD cases in Hangzhou from 2016 to 2018. Specimens from these cases were collected and tested for EV-A71, CV-A16, CV-A6, CV-A10, CV-A2, and CV-A5 by reverse transcriptase polymerase chain reaction. From 2016 to 2018, the prevalence of HFMD was seasonal each year. Among the 4760 probable HFMD cases, 3559 cases were confirmed (74.8%), including 426 cases of EV-A71 infections (8.9%), 249 cases of CV-A16 infections (5.2%), and 2884 cases of other EV infections (60.6%). The percentage of other EV infections was more than 80%, which increased year by year. Random selection of samples for detection of other EV infections in 2017 and 2018, among the 1297 cases, showed there were 835 (64.4%) cases of CV-A6 infections, 177 (13.6%) cases of CV-A10 infections, 100 (7.7%) cases of CV-A2 infections, 40 (3.1%) cases of CV-A5 infections, 3 (0.02 %) cases of mixed infections, and 11.0% untyped EV infections. Preschool children were still the primary population susceptible to HFMD. In severe cases, EV-A71 infection was the main cause. Characterizing the epidemiology and the relationship between severe and common cases of HFMD would provide relevant evidences for the prevention and treatment of HFMD.

Effects of temperature fluctuations on spatial-temporal transmission of hand, foot, and mouth disease.

Hand, foot, and mouth disease (HFMD), predominantly occurs among infants and children. Previous studies have shown that suitable, stable temperatures favor HFMD virus reproduction; however, temperature fluctuations also affect virus transmission, and there are, so far, no studies concerning the association between such fluctuations and the incidence of HFMD. The objective of this study was to map the spatial-temporal distribution of HFMD incidence and quantify the long-term effects of temperature fluctuations on HFMD incidence in children. HFMD cases in children under five, from January 2009 to December 2013, in Beijing, Tianjin, and Hebei provinces of China, were used in this study. The GeoDetector and Bayesian space-time hierarchy models were employed to explore the spatial-temporal association between temperature fluctuations and HFMD incidence. The results indicate that HFMD incidence had significant spatial stratified heterogeneity (GeoDetector q-statistic = 0.83, p < 0.05), and that areas with higher risk mainly appeared in metropolises and their adjacent regions. HFMD transmission was negatively associated with temperature fluctuations. A 1 °C increase in the standard deviation of maximum and minimum temperatures was associated with decreases of 8.22% and 11.87% in the risk of HFMD incidence, respectively. The study suggests that large temperature fluctuations affect virus growth or multiplication, thereby inhibiting the activity of the virus and potentially even leading to its extinction, and consequently affecting the spatial-temporal distribution of HFMD. The findings can serve as a reference for the practical control of this disease and offer help in the rational allocation of medical resources.

Hand-Foot-and-Mouth Disease: Rapid Evidence Review.

Hand-foot-and-mouth disease is caused by human enteroviruses and coxsackieviruses. Outbreaks can occur in the spring to fall and are common in North America, and most cases occur in patients younger than 10 years. Hand-foot-and-mouth disease is transmitted by fecal-oral, oral-oral, and respiratory droplet contact. Patients present with a low-grade fever, a maculopapular or papulovesicular rash on the hands and soles of the feet, and painful oral ulcerations. Lesions usually resolve in seven to 10 days; however, in rare cases, patients may have neurologic or cardiopulmonary complications. The differential diagnosis for childhood rashes and oral enanthems is broad and includes erythema multiforme, herpes, measles, and varicella. Treatment is supportive and directed toward hydration and pain relief as needed with acetaminophen or ibuprofen. Oral lidocaine is not recommended, and antiviral treatment is not available. The best methods to prevent the spread of hand-foot-and-mouth disease are handwashing and disinfecting potentially contaminated surfaces and fomites.

Necrotising fasciitis complicating hand, foot and mouth disease.

A literature search confirmed no previous cases of necrotising fasciitis (NF) complicating hand,foot and mouth disease (HFMD). This report explores the case of a previously well 55-week-old Caucasian boy who attended accident and emergency with an acutely swollen right hand and atypical viral rash affecting the hands and face. He was admitted under plastic surgery and treated with intravenous antibiotics and fluid resuscitation for sepsis secondary to cellulitis. Following dermatological review of the rash, a clinical diagnosis of atypical HFMD was made. He deteriorated over the first 12 hours with progression of cellulitis despite intervention. Emergency exploration and debridement were performed for suspected NF. NF was subsequently confirmed by laboratory testing. He required 5 days in paediatric intensive care but made a full recovery. Recent reports highlight an increase in atypical cases of HFMD. Clinicians should be aware of the potential for superadded necrotising infection in cases of atypical HFMD.

Assessing the efficacy and safety of magnesium sulfate for management of autonomic nervous system dysregulation in Vietnamese children with severe hand foot and mouth disease.

BACKGROUND: Brainstem encephalitis is a serious complication of hand foot and mouth disease (HFMD) in children. Autonomic nervous system (ANS) dysregulation and hypertension may occur, sometimes progressing to cardiopulmonary failure and death. Vietnamese national guidelines recommend use of milrinone if ANS dysregulation with Stage 2 hypertension develops. We wished to investigate whether magnesium sulfate (MgSO4) improved outcomes in children with HFMD if used earlier in the evolution of the ANS dysregulation (Stage 1 hypertension). METHODS: During a regional epidemic we conducted a randomized, double-blind, placebo-controlled trial of MgSO4 in children with HFMD, ANS dysregulation and Stage 1 hypertension, at the Hospital for Tropical Diseases in Ho Chi Minh city. Study participants received an infusion of MgSO4 or matched placebo for 72 h. We also reviewed data from non-trial HFMD patients in whom milrinone failed to control hypertension, some of whom received MgSO4 as second line therapy. The primary outcome for both analyses was a composite of disease progression within 72 h - addition of milrinone (trial participants only), need for ventilation, shock, or death. RESULTS: Between June 2014 and September 2016, 14 and 12 participants received MgSO4 or placebo respectively, before the trial was stopped due to futility. Among 45 non-trial cases with poorly controlled hypertension despite high-dose milrinone, 33 received MgSO4 while 12 did not. There were no statistically significant differences in the composite outcome between the MgSO4 and the placebo/control groups in either study (adjusted relative risk (95%CI) of [6/14 (43%) vs. 6/12 (50%)], 0.84 (0.37, 1.92), p = 0.682 in the trial and [1/33 (3%) vs. 2/12 (17%)], 0.16 (0.01, 1.79), p = 0.132 in the observational cohort). The incidence of adverse events was similar between the groups. Potentially toxic magnesium levels occurred very rarely with the infusion regime used. CONCLUSION: Although we could not demonstrate efficacy in these studies, there were no safety signals associated with use of 30-50 mg/kg/hr. MgSO4 in severe HFMD. Intermittent outbreaks of HFMD are likely to continue across the region, and an adequately powered trial is still needed to evaluate use of MgSO4 in controlling hypertension in severe HFMD, potentially involving a higher dose regimen. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01940250 (Registered 22 AUG 2013). Trial sponsor: University of Oxford.

Satisfactory usage of kidneys from pediatric donors with severe hand foot mouth disease.

No studies have reported making use of kidneys from pediatric donors with severe HFMD. Here, we retrospectively analyzed the feasibility and clinical effect of six cases of kidney transplantation from four pediatric donors with severe HFMD in our center between January 2014 and December 2016. The donors' age ranged from 6 months to 3 years and 11 months. The recipients' age ranged from 18 to 41 years. Single kidney transplantation was performed in four recipients, and dual splitting kidney transplantation and en bloc kidney transplantation were performed in two recipients, respectively. During the 1.5-4 years follow-up, all recipients maintained normal kidney allograft function except for one recipient whose allograft was removed due to the allograft artery thrombosis. The survival rates of recipient and allograft were 100% and 83.3%, respectively. None of the six recipients showed any symptoms associated with HFMD. In conclusion, it is feasible to perform kidney transplantation from pediatric donors with severe HFMD to adult recipients with immunity to the pathogens. The clinical effect is satisfactory.

[Effects of L-carnitine on serum levels of brain natriuretic peptide and N-terminal pro-brain natriuretic peptide and cardiac function in children with severe hand-foot-mouth disease].

OBJECTIVE: To observe the effects of L-carnitine treatment on serum levels of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) and cardiac function in children with heart dysfunction and severe hand-foot-mouth disease (HFMD). METHODS: A total of 120 children with severe HFMD were enrolled and randomly and equally divided into routine treatment group and L-carnitine treatment group. Thirty healthy children served as the control group. HFMD patients were given anti-fever and antiviral treatment as the basic treatment, while the patients in the L-carnitine treatment group were given L-carnitine as an adjuvant treatment to the basic treatment. Treatment outcomes were observed in the two groups. For all the subjects, serum levels of BNP and NT-proBNP and cardiac function parameters including left ventricular ejection fraction (LVEF), fractional shortening (FS), and cardiac index (CI) were measured at different time points before and after treatment. RESULTS: Before treatment, HFMD patients had significantly higher serum levels of BNP and NT-proBNP and heart rate but significantly lower LVEF, FS, and CI compared with the control group (P<0.05). After treatment, the L-carnitine treatment group had a significantly higher response rate than the routine treatment group (P<0.05). After 3 days of treatment, the serum levels of BNP and NT-proBNP, LVEF, FS, and CI were significantly reduced in the L-carnitine group (P<0.05); the L-carnitine group had significantly lower serum levels of BNP and NT-proBNP, LVEF, FS, and CI than the routine treatment group (P<0.05); there were no significant differences in the serum levels of BNP and NT-proBNP, LVEF, FS, or CI between the L-carnitine treatment and control groups (P>0.05). After 5 days of treatment, there were no significant differences in the serum levels of BNP and NT-proBNP, LVEF, FS, or CI between the L-carnitine treatment and routine treatment groups (P>0.05). Heart rate recovery was significantly slower in the routine treatment group than in the L-carnitine treatment group (P<0.05). CONCLUSIONS: As an adjuvant therapy for severe HFMD, L-carnitine treatment has satisfactory short-term efficacy in reducing the serum levels of BNP and NT-proBNP and improving cardiac function, thus improving clinical outcomes.

Case report: Features of hand, foot and mouth disease in neonates.

RATIONALE: Hand, foot and mouth disease (HFMD) is caused by enterovirus. The virus may exist in secretions. PATIENT CONCERNS: Five neonates had symptoms of fever and maculopapular rashes involving face, trunk, breech, arms, and legs, especially scattering on palms and feet. Blood, oropharyngeal fluid, urine, and cerebrospinal fluid (CSF) samples were collected and detected for further diagnoses with the consent of the infants' parents. Some of them suffered aseptic meningitis. DIAGNOSES: They were diagnosed as HFMD with CSF enterovirus positive. INTERVENTIONS: All of them continued breastfeed. Water bag was used during the pyrogenic stage. Antibiotics were administrated at first and withdrawn as soon as possible. OUTCOMES: None of them developed into brainstem encephalitis or pulmonary edema and they all recovered well. LESSONS: HFMD is more common in neonates than it has been thought. Enterovirus may exist in neonatal CSF and cause CSF cell to increase similar to purulent meningitis. Medical history, physical examination, and CSF enterovirus detection are important in making correct diagnosis. Unlike bacterial infection, HFMD is a self-limited disease. Once HFMD is determined and bacterial infection is ruled out, antibiotics should be avoided.

Clinical features for 89 deaths of hand, foot and mouth disease in Guangxi, China, 2014.

OBJECTIVES: The aim of this study is to summarize the risk factors of severe Hand, foot and mouth disease (HFMD) and explore the clinical characteristics of pulmonary edema (PE) and non-PE in the deceased patients with HFMD. METHODS: We identified 89 HFMD deaths which were separated into the PE group or non-PE group. Next, patients were divided based on their initial admission to hospitals as stage 1, 2, 3, or 4; at this point, their clinical manifestations were compared. RESULTS: There were 87 cases in the PE group, and 2 cases in the non-PE group. In the PE group, the difference in median time for patients at different stages from onset to symptoms, showed no significant difference (p>0.05). The etiology was detected as a positive rate for enterovirus 71 (EV71) of 89.19%, which showed a more severe course than other etiologies. The white blood cell (WBC) counts, lymphocyte (LYM) counts and creatine kinase MB (CK-MB) counts of patients admitted in different stages increased significantly with severity (p<0.05). CONCLUSIONS: There may be two clinical subtypes, mostly PE and rarely non-PE, in the deceased patients with HMFD. EV71 and risk factors such as an increased WBC count are associated with a severe course of HMFD.

Modelling person-to-person transmission in an Enterovirus A71 orally infected hamster model of hand-foot-and-mouth disease and encephalomyelitis.

Enterovirus A71 (EV-A71) causes hand-foot-and-mouth disease (HFMD), which may be complicated by fatal encephalomyelitis. Although fecal-oral or oral-oral routes are important in person-to-person transmission, how viral shedding and exposure may predispose individuals to infection remains unknown. We investigated person-to-person transmission by using a model of HFMD and encephalomyelitis based on EV-A71 oral infection of 2-week-old hamsters. Animals (index animals) infected with 104 50% cell culture infective doses of virus uniformly developed severe disease four days post-infection (dpi), whereas littermate contacts developed severe disease after six to seven days of exposure to index animals. Virus was detected in oral washes and feces at 3-4 dpi in index animals and at three to eight days after exposure to index animals in littermate contact animals. In a second experiment, non-littermate contact animals exposed for 8 or 12 h to index animals developed the disease six and four days post-exposure, respectively. Tissues from killed index and contact animals, studied by light microscopy, immunohistochemistry and in situ hybridization, exhibited mild inflammatory lesions and/or viral antigens/RNA in the squamous epithelia of the oral cavity, tongue, paws, skin, esophagus, gastric epithelium, salivary glands, lacrimal glands, central nervous system neurons, muscles (skeletal, cardiac and smooth muscles) and liver. Orally shed viruses were probably derived from infected oral mucosa and salivary glands, whereas fecal viruses may have derived from these sites as well as from esophageal and gastric epithelia. Asymptomatic seroconversion in exposed mother hamsters was demonstrated. Our hamster model should be useful in studying person-to-person EV-A71 transmission and how drugs and vaccines may interrupt transmission.

[Application of esmolol in severe hand, foot, and mouth disease].

OBJECTIVE: To study the clinical effect and mechanism of action of esmolol in the treatment of severe hand, foot, and mouth disease (HFMD). METHODS: A prospective randomized controlled trial was performed. A total of 102 children with severe HFMD were enrolled in the study and were randomly divided into conventional treatment and esmolol treatment groups (n=51 each). The children in the conventional treatment group were given conventional treatment according to the guidelines for the diagnosis and treatment of HFMD. Those in the esmolol treatment group were given esmolol in addition to the conventional treatment. The heart rate (HR), systolic blood pressure (SBP), and respiratory rate (RR) were continuously monitored for all children. Blood samples were collected from all children before treatment and 1, 3, and 5 days after treatment to measure the levels of norepinephrine (NE), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nuclear factor-kappa B (NF-κB) p65 in mononuclear cells. Serum levels of myocardial enzymes and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured before treatment and after 5 days of treatment. RESULTS: There were no significant differences in HR, SBP, RR, NE, TNF-α, IL-6, NF-κB p65, serum myocardial enzymes, and NT-proBNP before treatment between the conventional treatment and esmolol treatment groups. Both groups had significant reductions in these parameters at each time point (P<0.05). Compared with the conventional treatment group, the esmolol treatment group had significant improvements in the above parameters after 1 and 3 days of treatment (P<0.05). After 5 days of treatment, the esmolol treatment group had significant improvements in serum levels of myocardial enzymes and NT-proBNP compared with the conventional treatment group (P<0.05). CONCLUSIONS: Early application of esmolol can effectively stabilize the vital signs of the children with severe HFMD. Its mechanism of action may be related to reducing serum catecholamine concentration, alleviating myocardial damage, improving cardiac function, and reducing inflammatory response.

A Case-control Study on Risk Factors for Severe Hand, Foot and Mouth Disease.

The objective of this study was to identify potential risk factors for severe hand, foot and mouth disease (HFMD). In this case-control study, 459 severe HFMD patients and 246 mild HFMD patients from Guangdong province and Henan province, China were included. Data comprising demographic characteristics, clinical symptoms and signs, laboratory findings and other factors were collected. Univariate analysis revealed 30 factors associated with severe cases. Further multivariate analysis indicated four independent risk factors: fatigue (p < 0.01, odd ratio [OR] = 204.7), the use of glucocorticoids (p = 0.03, OR = 10.44), the use of dehydrant drugs (p < 0.01, OR = 73.7) and maculopapular rash (p < 0.01, OR = 84.4); and one independent protective factor: herpes or ulcers in mouth (p = 0.01, OR = 0.02). However, more systematic research and validation are needed to understand the underlying risk factors for severe HFMD.

Clinical significance of combined liver function and high-sensitivity C-reactive protein measurement in children with hand-foot-mouth disease.

Hand-foot-mouth disease (HFMD) is a common pediatric disease responsible for the development of rashes or herpes on the hand, foot, and mouth. Severe complications of HFMD include myocarditis, pulmonary edema, aseptic meningoencephalitis, and even death. Therefore, early diagnosis of HFMD is of particular importance. In this study, we determined the clinical value of the combined detection of liver function and high-sensitivity C-reactive protein (hs-CRP) expression in children with HFMD. Three hundred children with HFMD were recruited to this study between July 2013 and July 2015 and divided into the mild and severe HFMD groups (N = 150 per group). The liver function [aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) levels] and hs-CRP expression were evaluated using standardized tests, and the clinical value of combined detection of these indices (in parallel and serially) was determined. Patients in the severe HFMD group showed significantly higher levels of ALT, AST, ALP, and hs-CRP compared to those in the mild HFMD group (P < 0.05). The hs-CRP and liver function tests had low specificity and sensitivity, respectively. However, parallel combined detection improved the sensitivity and negative predicted value of these indices, whereas serial combined detection improved the specificity and positive predicted value. In conclusion, hs-CRP and liver function play a major role in the diagnosis of HFMD (and identifying its severity), and serial combined detection of these indices enhances the positive predicted value, and could be employed to diagnose severe HFMD at an earlier stage.

Gene sequencing and variable site analyzing of coding region of two enterovirus A71 isolates with different clinical phenotypes.

Currently, it is still controversial that if the pathogenicity of EV-A71 causing severe or mild hand, foot, and mouth disease (HFMD) is associated with viral nucleotide or amino acid sequence(s). In this study, 19 clinical strains were detected in samples from diagnosed patients of EV-A71-caused HFMD with mild or severe symptoms. Then, VP1-2A fragment sequences of 19 EV-A71 isolates were determined, the phylogenetic analysis, based on VP1 sequences of 19 EV-A71 stains in this study and which of 62 EV-A71 strains with different clinical phenotypes reported before, were carried out. Our results showed that no difference in the genotype and evolution distribution was observed among the EV-A71 strains mentioned above. Furthermore, two EV-A71 isolates, which with much close evolutionary relationship but different clinical manifestations, were purified by plaque assay, the complete genome sequencing was done, and deduced amino acid sequence analysis of 11 proteins coded by EV-A71 was carried out. Eight variable amino acid sites were found and further verified with those of 62 strains reported before. Our study provides further evidence that the potential pathogenicity of EV-A71 causing severe or mild HFMD seems not to be associated with viral genotype and even the amino acid substitution.

[Effect of continuous hemofiltration on inflammatory mediators and hemodynamics in children with severe hand, foot and mouth disease].

OBJECTIVE: To investigate the effect of continuous veno-venous hemofiltration (CVVH) on inflammatory mediators in children with severe hand, foot and mouth disease (HFMD), and to investigate its clinical efficacy. METHODS: A total of 36 children with stage IV HFMD were enrolled and randomly divided into conventional treatment group and CVVH group (n=18 each). The children in the CVVH group were given CVVH for 48 hours in addition to the conventional treatment. The levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and lactic acid in peripheral venous blood, heart rate, blood pressure, and left ventricular ejection fraction were measured before treatment and after 24 and 48 hours of treatment. RESULTS: After 24 hours of treatment, the conventional treatment group had a significantly reduced serum IL-2 level (P<0.01), and the CVVH treatment group had significantly reduced serum levels of IL-2, IL-6, IL-10, and TNF-α (P<0.05). After 48 hours of treatment, both groups had significantly reduced serum levels of IL-2, IL-6, IL-10, and TNF-α (P<0.01), and the CVVH group had significantly lower levels of these inflammatory factors than the conventional treatment group (P<0.01). After 48 hours of treatment, heart rate, systolic pressure, and blood lactic acid level were significantly reduced, and left ventricular ejection fraction was significantly increased in both groups, and the CVVH group had significantly greater changes in these indices except systolic pressure than the conventional treatment group (P<0.01). CONCLUSIONS: CVVH can effectively eliminate inflammatory factors, reduce heart rate and venous blood lactic acid, and improve heart function in children with severe HFMD.

Clinical Features for Mild Hand, Foot and Mouth Disease in China.

BACKGROUND: Mild hand, foot and mouth disease (HFMD) is at a critical stage owing to its ease of communicability and a higher risk of developing severe complications and death. Clinical diagnosis of mild HFMD was made by the presenting symptoms and signs (symptoms in brief) alone. We aim to evaluate the frequencies of symptoms in a retrospective case series study. METHODS: We collected epidemiological, demographic, clinical, and laboratory data from outpatient and inpatient settings on the clinical data warehouse system. We principally described the frequencies of symptoms of mild HFMD. Correlations between symptoms with laboratory-confirmed cases were then analyzed. RESULTS: The clinical data warehouse system included 3649 probable cases, between 2010 and 2012, of which 956 (26.20%) were laboratory confirmed. The peak incidence was identified in children 2 years of age. A total of 370 of the 956 laboratory confirmed cases (38.70%) were associated with enterovirus 71 (EV71). Logistic regression analysis adjusted for geographical variables, age, sex, month of onset, and time from onset to diagnosis showed that the clinical features constipation (P<0.0001; adjusted OR, 95%CI (2.99, 2.28-3.91)), and blisters (P<0.0001; adjusted OR, 95%CI (2.16, 1.82-2.56)) were positively correlated with the confirmed cases. CONCLUSIONS: This is the largest case series study, including all the guideline-mentioned symptoms of mild HFMD. Our findings suggest that blisters and constipation should be considered as potential warning signs while front-line clinicians manage surges of children diagnosed with mild HFMD during a pandemic.