Reflecting on the 1998 enterovirus outbreak: A 25-year retrospective and learned lessons.

Enterovirus A71 (EV-A71) infections pose a significant public health concern in the Asia-Pacific region. EV-A71 is primarily responsible for causing hand, foot, and mouth disease (HFMD) in children. However, this virus can also lead to severe and potentially fatal neurological consequences in affected individuals. This review aims to provide a comprehensive understanding of the molecular virology, epidemiology, and recombination events associated with EV-A71. The literature extensively covers the clinical manifestations and neurological symptoms that accompany EV-A71 infections. One of the complications explored in this review is brainstem encephalitis, which can arise as a result of EV-A71 infections. Brainstem encephalitis refers to inflammation of the brainstem, a critical region responsible for various bodily functions. The review examines the underlying mechanisms, diagnostic criteria, treatment options, and prognosis for central nervous system infections involving EV-A71. Neurological complications associated with EV-A71 infections are diverse and can have severe consequences. These complications may include aseptic meningitis, acute flaccid paralysis, and acute transverse myelitis. The review delves into the pathophysiology of these complications, shedding light on the molecular mechanisms through which EV-A71 affects the central nervous system. Accurate diagnosis of EV-A71 infections is crucial for appropriate management and treatment. Treatment options for EV-A71 infections primarily focus on supportive care, as there are currently no specific antiviral drugs available for this virus. The review highlights the importance of managing symptoms, such as fever, dehydration, and pain relief, to alleviate the burden on affected individuals. Prognosis for individuals with central nervous system (CNS) infections involving EV-A71 can vary depending on the severity of the complications. The review provides insights into the long-term outcomes and potential neurological sequelae associated with EV-A71 infections. In conclusion, EV-A71 infections have emerged as a major public health concern in the Asia-Pacific region. This review aims to enhance our understanding of the molecular virology, epidemiology, and neurological complications associated with EV-A71. By examining the underlying mechanisms, diagnostic criteria, treatment options, and prognosis, this review contributes to the development of effective strategies for the prevention, diagnosis, and management of EV-A71 infections. The paper presents a comprehensive analysis of worldwide data pertaining to outbreaks of EV-A71 and HFMD. The subsequent discourse delves into the advancement and strategic formulation pertaining to the creation of vaccines targeting EV-A71. In summary, this study provides a comprehensive examination of the potential obstacles and considerations involved in the management and treatment of EV-A71 infections. Additionally, it proposes suggestions for future research and development endeavors with the objective of formulating efficacious treatment approaches for this viral infection.

Predicting factors for acute encephalopathy in febrile seizure children with SARS-CoV-2 omicron variant: a retrospective study.

BACKGROUND: SARS-CoV-2 posed a threat to children during the early phase of Omicron wave because many patients presented with febrile seizures. The study aimed to investigate predicting factors for acute encephalopathy of children infected by SARS-CoV-2 Omicron variant presenting with febrile seizures. METHODS: The retrospective study analyzed data from pediatric patients who visited the emergency department of Chang Gung Memorial Hospital in Taiwan between April and July 2022. We specifically focused on children with COVID-19 who presented with febrile seizures, collecting demographic, clinical, and laboratory data at the pediatric emergency department, as well as final discharge diagnoses. Subsequently, we conducted a comparative analysis of the clinical and laboratory characteristics between patients diagnosed with acute encephalopathy and those with other causes of febrile seizures. RESULTS: Overall, 10,878 children were included, of which 260 patients presented with febrile seizures. Among them, 116 individuals tested positive for SARS-CoV-2 and of them, 14 subsequently developed acute encephalopathy (12%). Those with acute encephalopathy displayed distinctive features, including older age (5.1 vs. 2.6 years old), longer fever duration preceding the first seizure (1.6 vs. 0.9 days), cluster seizure (50% vs. 16.7%), status epilepticus (50% vs. 13.7%) and occurrences of bradycardia (26.8% vs. 0%) and hypotension (14.3% vs. 0%) in the encephalopathy group. Besides, the laboratory findings in the encephalopathy group are characterized by hyperglycemia (mean (95% CI) 146 mg/dL (95% CI 109-157) vs. 108 mg/dL (95% CI 103-114) and metabolic acidosis (mean (95% CI) pH 7.29(95% CI 7.22-7.36) vs. 7.39 (95%CI 7.37-7.41)). CONCLUSIONS: In pediatric patients with COVID-19-related febrile seizures, the occurrence of seizures beyond the first day of fever, bradycardia, clustered seizures, status epilepticus, hyperglycemia, and metabolic acidosis should raise concerns about acute encephalitis/encephalopathy. However, the highest body temperature and the severity of leukocytosis or C-reactive protein levels were not associated with poor outcomes.

Prognostic Factors in Children with Acute Kidney Injury Requiring Continuous Renal Replacement Therapy.

INTRODUCTION: This study aims to evaluate prognostic factors and outcomes in a single-center PICU cohort that received continuous renal replacement therapy (CRRT). METHODS: This retrospective study analyzed clinical characteristics, laboratory data, and outcomes. Ninety-day mortality and advanced chronic kidney disease (CKD) (eGFR <60 ml/min/1.73m2) were defined as primary and secondary outcomes, respectively. RESULTS: Seventy-five patients were enrolled, all of whom received CRRT for indications including acute kidney injury with complicated refractory metabolic acidosis, electrolyte derangement, and existed or impending fluid overload. The 90-day mortality and advanced CKD were 53% and 29%, respectively. Multivariate Cox regression analysis demonstrated that only underlying bone marrow transplantation (BMT) (HR 4.58; 95% CI 2.04-10.27) and a high pSOFA score (HR 1.12; 95% CI 1.01-1.23) were independent risk factors for 90-day mortality. Among survivors, ten developed advanced CKD on the 90th day, and this group had a higher serum fibrinogen level (OR 1.01; 95% CI 1.01-1.03) at the start of CRRT. CONCLUSION: In critically ill children with AKI requiring CRRT, post-BMT and high pSOFA scores are independent risk factors for 90-day mortality. Additionally, a high serum fibrinogen level at the initiation of CRRT is associated with the development of advanced CKD.

Ferritin as an Effective Predictor of Neurological Outcomes in Children With Acute Necrotizing Encephalopathy.

BACKGROUND: Acute necrotizing encephalopathy (ANE) is a fulminant disease with poor prognosis. Cytokine storm is the important phenomenon of ANE that affects the brain and multiple organs. The study aimed to identify whether hyperferritinemia was associated with poor prognosis in patients with ANE. METHODS: All patients with ANE had multiple symmetric lesions located in the bilateral thalami and other regions such as brainstem tegmentum, cerebral white matter, and cerebellum. Neurological outcome at discharge was evaluated by pediatric neurologists using the Pediatric Cerebral Performance Category Scale. All risk factors associated with poor prognosis were further analyzed using receiver operating characteristic curve analysis. RESULTS: Twenty-nine patients with ANE were enrolled in the current study. Nine (31%) patients achieved a favorable neurological outcome, and 20 (69%) patients had poor neurological outcomes. results The group of poor neurological outcome had significantly higher proportion of shock on admission and brainstem involvement. Based on multivariate logistic regression analysis, ferritin, aspartate aminotransferase (AST), and ANE severity score (ANE-SS) were the predictors associated with outcomes. The appropriate cutoff value for predicting neurological outcomes in patients with ANE was 1823 ng/mL for ferritin, 78 U/L for AST, and 4.5 for ANE-SS. Besides, comparison analyses showed that higher level of ferritin and ANE-SS were significantly correlated with brainstem involvement (P < 0.05). CONCLUSIONS: Ferritin may potentially be a prognostic factor in patients with ANE. Hyperferritinemia is associated with poor neurological outcomes in patients with ANE and ferritin levels more than 1823 ng/mL have about eightfold increased risk of poor neurological outcome.

In-hospital care of children with COVID-19.

Children have been reported to be less affected and to have milder severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than adults during the coronavirus disease 2019 (COVID-19) pandemic. However, children, and particularly those with underlying disorders, are still likely to develop critical illnesses. In the case of SARS-CoV-2 infection, most previous studies have focused on adult patients. To aid in the knowledge of in-hospital care of children with COVID-19, this study presents an expert review of the literature, including the management of respiratory distress or failure, extracorporeal membrane oxygenation (ECMO), multisystem inflammatory syndrome in children (MIS-C), hemodynamic and other organ support, pharmaceutical therapies (anti-viral drugs, anti-inflammatory or antithrombotic therapies) and management of cardiopulmonary arrest.

Diastolic blood pressure impact on pediatric refractory septic shock outcomes.

BACKGROUND: Septic shock is the progression of sepsis, defined as cardiovascular dysfunction during systemic infection, and it has a mortality rate of 40 %-80 %. Loss of vascular tone is an important pathophysiological feature of septic shock. Diastolic blood pressure (DBP) was reported to be associated with vascular tone. This study aimed to identify the associations of several hemodynamic indices, especially DBP, with outcome in pediatric septic shock to allow for timely interventions. METHODS: Children with persistent catecholamine-resistant shock had a pulse index continuous cardiac output (PiCCO®) system implanted for invasive hemodynamic monitoring and were enrolled in the current study. Serial cardiac index, systemic vascular resistance index (SVRI), systolic blood pressure (SBP), mean arterial pressure (MAP), and DBP were recorded during the first 24 h following PiCCO® initiation. All hemodynamic parameters associated with 28-day mortality were further analyzed using receiver operating characteristic curve analysis. RESULTS: Thirty-three children with persistent catecholamine-resistant shock were enrolled. The median age was 12 years and the youngest children were 5 years old. Univariate analysis noted that SVRI, SBP, MAP, and DBP were significantly higher, and shock index was significant lower, in survivors compared with non-survivors (p < 0.05). In the multivariate analysis, only SVRI and DBP remained independent predictors of 28-day mortality. DBP had the best correlation with SVRI (r = 0.718, n = 219, p < 0.001). The area under the receiver operating characteristic curves of SVRI and DBP for predicting 28-day mortality during the first 24 h of persistent catecholamine-resistant shock were >0.75, indicating a good prediction for mortality. CONCLUSIONS: DBP correlated well with SVRI and it can serve as a predictor for mortality in pediatric septic shock. Furthermore, DBP was a superior discriminator of mortality when compared with SBP and MAP. A lower DBP was an independent hemodynamic factor associated with 28-day mortality.

Predictors of neurologic outcomes and mortality in physically abused and unintentionally injured children: a retrospective observation study.

OBJECTIVES: This study aimed to identify the predictors of neurologic outcomes and mortality in physically abused and unintentionally injured children admitted to intensive care units (ICUs). METHODS: All maltreated children were admitted to pediatric, neurosurgical, and trauma ICUs between 2001 and 2019. Clinical factors, including age, sex, season of admission, identifying settings, injury severity score, etiologies, length of stay in the ICU, neurologic outcomes, and mortality, were analyzed and compared between the physically abused and unintentionally injured groups. Neurologic assessments were conducted using the Pediatric Cerebral Performance Category scale. The study was approved by the Institutional Review Board of Chang Gung Memorial Hospital and the Ethics Committee waived the requirement for informed consent because of the anonymized nature of the data. RESULTS: A total of 2481 children were investigated; of them, there were 480 (19.3%) victims admitted to the ICUs, including 156 physically abused and 324 unintentionally injured. Age, history of prematurity, clinical outcomes, head injury, neurosurgical interventions, clinical manifestations, brain computed tomography findings, and laboratory findings significantly differed between them (all p < 0.05). Traumatic brain injury was the major etiology for admission to the ICU. The incidence of abusive head trauma was 87.1% among the physically abused group. Only 46 (29.4%) and 268 (82.7%) cases achieved favorable neurologic outcomes in the physically abused and unintentionally injured groups, respectively. Shock within 24 h, spontaneous hypothermia (body temperature, < 35 °C), and post-traumatic seizure were strongly associated with poor neurologic outcomes and mortality in both groups. CONCLUSIONS: Initial presentation with shock, spontaneous hypothermia at ICU admission, and post-traumatic seizure were associated with poor neurologic outcomes and mortality in physically abused and unintentionally injured children.

Predictors of disease severity and outcomes in pediatric patients with croup and COVID-19 in the pediatric emergency department.

BACKGROUND: Croup caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging disease, and data on the risk factors associated with disease severity are still limited. The Westley croup score (WS) is widely used to assess croup severity. The current study aimed to analyze biomarkers associated with the WS and clinical outcomes in patients with croup and coronavirus disease 2019 in the pediatric emergency department (PED). POPULATION AND METHOD: Patients diagnosed with croup caused by SARS-CoV-2 were admitted at two PEDs. Clinical data including age, WS, length of hospital stay, initial laboratory data, and treatment were analyzed. Clinical parameters were evaluated via multivariate logistic regression analysis. The best cutoff values for predicting croup severity and outcomes were identified using the receiver operating characteristic curve. RESULT: In total, 250 patients were assessed. Moreover, 128 (51.2%) patients were discharged from the PED, and 122 (48.8%) were admitted to the hospital. Mild, moderate, and severe croup accounted for 63.6% (n = 159), 32% (n = 80), and 4.4% (n = 11) of all cases, respectively. A high mean age (years), neutrophil count (%), neutrophil-to-lymphocyte ratio (NLR), ALT (U/L), procalcitonin (ng/mL), and hemoglobin (g/dL) level, and length of hospital stay (days), and a low lymphocyte count (%) and blood pH were associated with croup severity and need for intensive care. Based on the multivariate logistic regression model, the NLR remained independent factors associated with croup severity and prognosis. Further, NLR was significantly correlated with WS. The area under the receiver operating characteristic curve of NLR for predicting a WS of ≥3 was 0.895 (0.842-0.948, p < 0.001), and that for predicting ICU admission was 0.795 (0.711-0.879, p < 0.001). The best cutoff values for a WS of ≥3 and ICU admission were 1.65 and 2.06, respectively. CONCLUSION: NLR is correlated with WS and is a reliable, easy-to-use, and cheap biomarker for the early screening and prognosis of croup severity in the PED. A higher NLR may indicate severe croup and the need for further treatment. And the WS score remains reliable for estimating the severity of croup caused by SARS-CoV-2 and the risk of intensive care.

MRI of fatal course of acute hemorrhagic leukoencephalitis in a child with SARS-CoV-2 omicron BA 2.0 infection.

We present a pediatric case of acute hemorrhagic leukoencephalitis associated with SARS-CoV-2 Omicron BA 2.0 infection. A previously healthy girl presented with ataxia and diplopia three weeks after the COVID-19 confirmation from a nasopharyngeal swab. Acute and symmetrical motor weakness and drowsiness ensued within the following 3 days. She then became spastic tetraplegic. MRI revealed multifocal lesions in the cerebral white matter, basal ganglia, and brainstem, with hemorrhagic changes confirmed with T1-hyperintensity and hypointensity on susceptibility-weighted images. Peripheral areas of decreased diffusion, increased blood flow, and rim contrast enhancement were noted in the majority of lesions. She was treated with a combination of intravenous immunoglobulin and methylprednisolone pulse therapy. Neurological deterioration ensued with coma, ataxic respiratory pattern and decerebrate posture. Repeated MRI performed on day 31 revealed progression of abnormalities, hemorrhages and brain herniation. Despite the administration of plasma exchange, she died two months after admission.

Electrographic Seizures in Neonates with a High Risk of Encephalopathy.

Background: Neonatal encephalopathy is caused by a wide variety of acute brain insults in newborns and presents with a spectrum of neurologic dysfunction, such as consciousness disturbance, seizures, and coma. The increased excitability in the neonatal brain appears to be highly susceptible to seizures after a variety of insults, and seizures may be the first clinical sign of a serious neurologic disorder. Subtle seizures are common in the neonatal period, and abnormal clinical paroxysmal events may raise the suspicion of neonatal seizures. Continuous video electroencephalographic (EEG) monitoring is the gold standard for the diagnosis of neonatal seizures. The aim of this study was to identify the prevalence of electrographic seizures and the impact of monitoring in neonates with a high risk of encephalopathy. Methods: We conducted this prospective cohort study in a tertiary neonatal intensive care unit over a 4-year period. Neonates with a high risk of encephalopathy who were receiving continuous video EEG monitoring were eligible. The patients were divided into 2 groups: (1) acute neonatal encephalopathy (ANE) and (2) other high-risk encephalopathy conditions (OHRs). The neonates' demographic characteristics, etiologies, EEG background feature, presence of electrographic seizures and the impact of monitoring were analyzed. Results: A total of 71 neonates with a high risk of encephalopathy who received continuous video EEG monitoring were enrolled. In this consecutive cohort, 42 (59.2%) were monitored for ANE and 29 (40.8%) were monitored for OHRs. At the time of starting EEG monitoring, 54 (76.1%) of the neonates were term infants. The median gestational age at monitoring was 39 weeks (interquartile range, 37−41 weeks). The median total EEG monitoring duration was 64.7 h (interquartile range, 22.2−72.4 h). Electrographic seizures were captured in 25 of the 71 (35.2%) neonates, of whom 20 (80%) had electrographic-only seizures without clinical correlation. Furthermore, of these 20 neonates, 13 (65%) developed electrographic status epilepticus. Electrographic seizures were most commonly found in the ANE group (17, 40.5%) than in the OHRs group (8, 27.6%) (p = 0.013). Besides, normal/mild abnormality and inactive EEG background were less electrographic seizure than moderate and major abnormality EEG background (2 of 30, 6.7% vs. 23 of 41, 56.1%, p < 0.001). Finally, continuous video EEG monitoring excluded the diagnosis of electrographic seizures in two-thirds of the monitored neonates who had paroxysmal events mimicking seizures and led to a change in clinical management in 39.4% of the neonates. Conclusions: Our findings showed that monitoring could accurately detect seizures, and that it could be used to guide seizure medication management. Therefore, continuous video EEG monitoring has important clinical management implications in neonates with a high risk of encephalopathy.

Risk Factors and Neurologic Outcomes Associated With Resuscitation in the Pediatric Intensive Care Unit.

In the pediatric intensive care unit (PICU), cardiac arrest (CA) is rare but results in high rates of morbidity and mortality. A retrospective chart review of 223 patients who suffered from in-PICU CA was analyzed from January 2017 to December 2020. Outcomes at discharge were evaluated using pediatric cerebral performance category (PCPC). Return of spontaneous circulation was attained by 167 (74.8%) patients. In total, only 58 (25%) patients survived to hospital discharge, and 49 (21.9%) of the cohort had good neurologic outcomes. Based on multivariate logistic regression analysis, vasoactive-inotropic drug usage before CA, previous PCPC scale >2, underlying hemato-oncologic disease, and total time of CPR were risk factors associated with poor outcomes. Furthermore, we determined the cutoff value of duration of CPR in predicting poor neurologic outcomes and in-hospital mortality in patients caused by in-PICU CA as 17 and 23.5 min respectively.

Cutoff Values of Hemodynamic Parameters in Pediatric Refractory Septic Shock.

Background: Refractory septic shock can cause severe morbidities and mortalities in children. Resuscitation based on hemodynamics is important in children with critical illness. Thus, this study aimed to identify the hemodynamics of refractory septic shock associated with poor prognosis at an early stage to allow for timely interventions. Methods: We evaluated children with refractory septic shock admitted to a pediatric intensive care unit (PICU) and monitored their hemodynamics using a pulse index continuous cardiac output (PiCCO) system. The serial cardiac index (CI), systemic vascular resistance index (SVRI), and vasoactive−inotropic score (VIS) were recorded during the first 72 h after PICU admission. Results: Thirty-three children with refractory septic shock were enrolled. The SVRI and VIS were both associated with fatality from septic shock. The non-survivors had lower serial SVRI and higher VIS (both p < 0.05). Based on the area under the ROC curve, the SVRI was the predictor during the early resuscitative stage (first 36 h) in pediatric refractory septic shock. Conclusions: Both SVRI and VIS are predictors of mortality in children with refractory septic shock, and the SVRI is the powerful predictor of mortality in the early resuscitative stage. A low serial SVRI may allow for the early awareness of disease severity and strategies for adjusting vasoactive−inotropic agents to increase the SVRI.

Early High-Dose Methylprednisolone Therapy Is Associated with Better Outcomes in Children with Acute Necrotizing Encephalopathy.

BACKGROUND: The neurologic outcomes of acute necrotizing encephalopathy (ANE) are very poor, with a mortality rate of up to 40% and fewer than 10% of patients surviving without neurologic deficits. Steroid and immunoglobulin treatments have been the most commonly used options for ANE, but their therapeutic efficacy is still controversial. METHOD: We retrospectively reviewed the medical records of 26 children diagnosed with ANE. We also divided these patients into two groups: 21 patients with brainstem involvement and 8 patients without brainstem involvement. Pulse steroid therapy (methylprednisolone at 30 mg/kg/day for 3 days) and intravenous immunoglobulin (2 g/kg for 2-5 days) were administered to treat ANE. RESULTS: The overall mortality rate was 42.3%, and patients who did not survive had significantly higher initial lactate and serum ferritin levels, as well as higher rates of inotropic agent use with brainstem involvement. There were no significant differences in the outcomes of pulse steroid therapy or pulse steroid plus immunoglobulin between survivors and non-survivors. When analyzing the time between symptom onset and usage of pulse steroid therapy, pulse steroid therapy used within 24 h after the onset of ANE resulted in significantly better outcomes (p = 0.039). In patients with brainstem involvement, the outcome was not correlated with pulse steroid therapy, early pulse steroid therapy, or pulse steroid therapy combined with immunoglobulin. All patients without brainstem involvement received "early pulse methylprednisolone" therapy, and 87.5% (7/8) of these patients had a good neurologic outcome. CONCLUSION: Pulse steroid therapy (methylprednisolone at 30 mg/kg/day for 3 days) administered within 24 h after the onset of ANE may be correlated with a good prognosis. Further studies are needed to establish a consensus guideline for this fulminant disease.

The Frequency of Clinical Seizures in Paroxysmal Events in a Neonatal Intensive Care Unit.

BACKGROUND: In general clinical practice, neonatal seizures are identified visually by direct clinical observation. The study aimed to examine the frequency of clinical seizures in paroxysmal events in a neonatal intensive care unit. METHODS: We conducted a prospective study of continuous video-EEG monitoring in a neonatal intensive care unit between January 2017 and December 2020. The demographic data were also reviewed. RESULTS: Sixty-four neonates were enrolled. The median total video-EEG monitoring duration was 24.1 h (IQR 17.5-44.8 h). There were 309 clinically suspected seizure episodes, of which 181 (58.6%) were the motor type and 128 (41.4%) were the non-motor type. Only 63 (20.4%) of these events were confirmed to be clinical seizures on a simultaneous video-EEG recording. In terms of the impact of continuous video-EEG monitoring on clinical management, the anti-epileptic drugs were changed in 42 (65.6%) of the 64 neonates. CONCLUSION: In the identification of neonatal seizures, a clinical diagnosis by direct observation alone is not enough. The use of continuous video-EEG monitoring plays an important role in the diagnosis of neonatal seizures and in guiding clinical management decisions.

Life-Threatening Enterovirus 71 Encephalitis in Unrelated Children with Autosomal Dominant TLR3 Deficiency.

PURPOSE: Enterovirus A71 (EV71) causes a broad spectrum of childhood diseases, ranging from asymptomatic infection or self-limited hand-foot-and-mouth disease (HFMD) to life-threatening encephalitis. The molecular mechanisms underlying these different clinical presentations remain unknown. We hypothesized that EV71 encephalitis in children might reflect an intrinsic host single-gene defect of antiviral immunity. We searched for mutations in the toll-like receptor 3 (TLR3) gene. Such mutations have already been identified in children with herpes simplex virus encephalitis (HSE). METHODS: We sequenced TLR3 and assessed the impact of the mutations identified. We tested dermal fibroblasts from a patient with EV71 encephalitis and a TLR3 mutation and other patients with known genetic defects of TLR3 or related genes, assessing the response of these cells to TLR3 agonist poly(I:C) stimulation and EV71 infection. RESULTS: Three children with EV71 encephalitis were heterozygous for rare mutations-TLR3 W769X, E211K, and R867Q-all of which were shown to affect TLR3 function. Furthermore, fibroblasts from the patient heterozygous for the W769X mutation displayed an impaired, but not abolished, response to poly(I:C). We found that TLR3-deficient and TLR3-heterozygous W769X fibroblasts were highly susceptible to EV71 infection. CONCLUSIONS: Autosomal dominant TLR3 deficiency may underlie severe EV71 infection with encephalitis. Human TLR3 immunity is essential to protect the central nervous system against HSV-1 and EV71. Children with severe EV71 infections, such as encephalitis in particular, should be tested for inborn errors of TLR3 immunity.

Hemodynamic monitoring and management of pediatric septic shock.

Sepsis remains a major cause of morbidity and mortality among children worldwide. Furthermore, refractory septic shock and multiple organ dysfunction syndrome are the most critical groups which account for a high mortality rate in pediatric sepsis, and their clinical course often deteriorates rapidly. Resuscitation based on hemodynamics can provide objective values for identifying the severity of sepsis and monitoring the treatment response. Hemodynamics in sepsis can be divided into two groups: basic and advanced hemodynamic parameters. Previous therapeutic guidance of early-goal directed therapy (EGDT), which resuscitated based on the basic hemodynamics (central venous pressure and central venous oxygen saturation (ScvO2)) has lost its advantage compared with "usual care". Optimization of advanced hemodynamics, such as cardiac output and systemic vascular resistance, has now been endorsed as better therapeutic guidance for sepsis. Despite this, there are still some important hemodynamics associated with prognosis. In this article, we summarize the common techniques for hemodynamic monitoring, list important hemodynamic parameters related to outcomes, and update evidence-based therapeutic recommendations for optimizing resuscitation in pediatric septic shock.

Household cleaning products poisoning in a pediatric emergency center: A 10- year cross-sectional study and literature review.

BACKGROUND: Poisoning by household cleaning products(HCPs) is common in children. Some HCPs are toxic and may cause severe complications. We assessed HCP poisonings treated in a pediatric emergency department(PED). METHODS: This was a retrospective study of patients aged under 18 years with HCP poisoning admitted to the largest PED in Taiwan from 2011 to 2020 were recruited. RESULTS: The records over a 10-year period from 103 children admitted to the PED because of HCP poisoning(70 boys [68%] and 33 girls [32%]), mean age 3.54 years(standard deviation [SD] = 3.15 years) were evaluated. Most poisonings were unintentional(99%, n = 102) and occurred at home(96%, n = 99). The HCPs included alkaline(74%, n = 76), acidic(25%, n = 26), and neutral(1%, n = 1) agents. Most were orally ingested(86%, n = 89). Panendoscopy was performed in 25 patients(24%), and the endoscopic(Zargar) grade was used to determine the severity of injury. Medications(steroids [9%, n = 9], antibiotics [10%, n = 10], or antacids [30%, n = 23]) were prescribed. Alkaline HCP ingestion induced severe esophageal injury(p = 0.04) and esophageal stricture(p = 0.04). Five patients(5%) exhibited esophageal strictures and required balloon dilation. On multivariate analysis, alkaline HCP ingestion(p = 0.04), severe esophageal caustic injury(Zargar grade ≥ 3) (p < 0.001), and medications(steroids [p < 0.001], antibiotics [p < 0.001], and antacids [p = 0.001]) were associated with esophageal stricture. CONCLUSION: Alkaline HCP ingestion and severe esophageal caustic injury(Zargar grade ≥ 3) were associated with esophageal stricture. Physicians tended to prescribe medications(steroids, antibiotics, or antacids) for patients with severe esophageal injuries to reduce the risk of esophageal stricture. The usefulness of these medications requires further study.

Risk Factors for Tracheobronchomalacia in Preterm Infants With Bronchopulmonary Dysplasia.

Aim: To identify the risk factors associated with the development of tracheobronchomalacia (TBM) in preterm infants with bronchopulmonary dysplasia (BPD). Methods: This was a retrospective cohort study using chart reviews of preterm infants born at ≤ 36 week's gestation who underwent flexible fiberoptic bronchoscopy in a tertiary pediatric referral center between January 2015 and January 2020. Indications for the bronchoscopy examination included lobar atelectasis on plain chest film, persistent CO2 retention, recurrent extubation failure, or abnormal breathing sounds such as wheeze or stridor. Optimal cutoff values for each risk factor were also determined. Results: Fifty-eight preterm infants with BPD were enrolled, of whom 29 (50%) had TBM. There were no significant differences in gestational age and birth weight between those with and without TBM. Significantly more of the patients with TBM had severe BPD compared to those without TBM (68.9 vs. 20.6%, p < 0.001). Clinical parameters that were significantly different between the two groups were included in multivariate analysis. Among these factors, severe BPD was the most powerful risk factor for the development of TBM (odds ratio 5.57, 95% confidence interval 1.32-23.5, p = 0.019). The areas under the receiver operating characteristic curves for peak inspiratory pressure (PIP) and the duration of intubation were 0.788 and 0.75, respectively. The best predictive cutoff values of PIP and duration of intubation for TBM were 18.5 mmHg and 82 days, respectively. Conclusion: Preterm infants with severe BPD are at high risk for the development of TBM, and the risk is even higher in those who receive a higher PIP or are intubated for longer. Bronchoscopy examinations should be considered for the early diagnosis and management of TBM in infants with these risk factors.

Clinical survey and predictors for the development of tracheobronchomalacia in preterm infants.

BACKGROUND: Tracheobronchomalacia (TBM) contributes to the increased morbidity and mortality observed in preterm infants. Effective strategies for the prevention of TBM are necessary to achieve better outcomes. We sought to identify risk factors associated with the development of TBM in preterm infants. Optimal cut-off values for each risk factor were also determined. METHODS: A total of 80 infants who were born at 36 week's gestation or earlier and underwent flexible bronchoscopy were included in our study sample. A comparison of demographic and clinical risk factors between those with TBM (n = 35, 44%) and those without TBM (n = 45, 56%) was conducted using multivariate logistic regression analysis. Receiver operating characteristic curve analysis was performed to determine the appropriate cut-off values for predicting the development of TBM. RESULTS: In the multivariate analysis, only peak inspiratory pressure (PIP) and the number of intubation days remained significantly different between infants with and without TBM. Preterm infants with TBM received higher PIP (odds ratio: [OR], 1.067; 95% confidence interval [CI], 1.010-1.128; p = .020) and were intubated for longer (odds ratio [OR], 1.019; 95% CI, 1.003-1.035; p = .016) than those without TBM. Infants who received PIP > 19.5 cmH2 O or were intubated for >79.5 days were associated with a significantly higher risk of presence of TBM. CONCLUSION: High PIP and prolonged intubation were major risk factors for the development of TBM in premature infants. Those who require PIP > 19.5 cmH2 O or intubation >79.5 days warrant bronchoscopy examination for early diagnosis and management of TBM.