Acute kidney injury in pediatric toxic shock syndrome is associated with worse clinical course in the intensive care unit.

To explore the prevalence, severity, nature, and significance of acute kidney injury (AKI) among children admitted to the pediatric intensive care unit (PICU) with toxic shock syndrome (TSS). Bi-center, retrospective observational study. Children admitted for TSS to two intensive care units from 2009-2022 were included. We identified 41 children (median age 5 years, 46% females) who met the Centers for Disease Control and Prevention (CDC) definitions of TSS. Staphylococcal TSS accounted for 63% of the patients and Streptococcal TSS accounted for the remaining 37%. AKI was diagnosed in 24 (59%) (stage 1: n = 6 [15% of total], stage 2: n = 10 [24%], and stage 3: n = 8 [20%]). The worst creatinine level was measured during the first day of admission in 34 (83%) patients. The median duration of AKI was 2 days. Creatinine normalized by hospital discharge in all cases. Patients with AKI had a longer intensive care unit stay than those without AKI (6 vs. 3 days, respectively, p = 0.01), needed more respiratory support (87% vs. 47%, p = 0.002), had fewer 28 ventilation-free days (25 vs. 28, p = 0.01), fewer vasopressor-free days (25 vs. 28, p = 0.001), and received more blood products (p = 0.03).    Conclusion: Children admitted to the PICU with TSS, show a high prevalence of AKI at presentation. Creatinine levels and clearance normalize by hospital discharge in most cases. AKI in the setting of TSS could be used as an early marker for illness severity and a predictor of a more complex course. What is Known: • TSS is characterized according to the CDC by specific sets of clinical signs and symptoms in conjunction with specific laboratory findings one of which is AKI. • AKI is associated with worse outcomes in critically ill patients in general and in septic patients in particular. What is New: • AKI is found in about 60% of all patients admitted to the PICU with a diagnosis of TSS and hence is an important defining criteria. • AKI in the setting of TSS is associated with a more complex illness course and can serve as an early marker predicting such a course.

Cerebrospinal fluid characteristics of patients treated with intrathecal nusinersen for spinal muscular atrophy.

INTRODUCTION/AIMS: There is limited information on the potential effects of repeated intrathecal antisense oligonucleotide drug delivery on cerebrospinal fluid (CSF) biochemical and blood cell profiles. This study aimed to examine longitudinal changes in the biochemical components (glucose, protein) and blood cell counts in the CSF of spinal muscular atrophy (SMA) patients treated with intrathecal nusinersen. METHODS: We collected and analyzed clinical and CSF parameters (cell count, protein, glucose, culture) of 50 individuals with SMA during nusinersen treatment (22 type 1, 17 type 2, and 11 type 3). RESULTS: The median protein concentration at baseline and during treatment was within the normal range but rose during treatment and was significantly above baseline at the time of the ninth intrathecal injection (p = 0.02, two-tailed Wilcoxon matched-pairs test, and p = 0.0015, Friedman test for repeated measures). Further analysis showed that the increase in CSF protein concentration was evident for SMA types 2 and 3 patients, but not for type 1. This observation was also demonstrated by a significant correlation between the SMN2 gene copy number and the increase in CSF protein concentration (Spearman rank correlation test). DISCUSSION: Our results demonstrate that a delayed increase in CSF protein concentration is expected during nusinersen treatment for SMA types 2 and 3. This might reflect the medication's effect and a possible therapeutic biochemical marker.

Weaning Strategy of Diuretics in Outpatient Preterm Infants with Bronchopulmonary Dysplasia: A National Survey.

OBJECTIVE: Long-term diuretic treatment in patients with bronchopulmonary dysplasia (BPD) is common despite lack of data that support its use. We aimed to characterize the commonly used diuretics weaning strategies for outpatient clinically stable preterm infants with BPD. STUDY DESIGN: We conducted a cross-sectional web-based survey among all pediatric pulmonologists and neonatologists in Israel. Questionnaire included data regarding practitioners' different diuretics-weaning practice in this population. RESULTS: The response rate for pulmonologists and neonatologists were 35/50 (70%) and 36/120 (30%), respectively. When both oxygen and diuretics are used, 59% wean oxygen first and 32% wean diuretics first. If patients are solely on diuretics, 27% discontinue instantly, 34% decrease the dosage gradually, and 34% outgrow the discharge dosage. Significantly more pulmonologists decrease the dosage gradually, while more neonatologists discontinue at once (p < 0.001). Most participants (94%) reported being unsatisfied with the existing data and guidelines regarding these issues. CONCLUSION: Our results showed a wide range of practice patterns in the weaning strategy of diuretics in outpatient preterm infants with BPD. Pulmonologists and neonatologists differ significantly in their weaning strategy. A prospective larger controlled study to explore the outcome of gradual tapering versus discontinuation without weaning is warranted. KEY POINTS: · Diuretic treatment in patients with BPD is common despite lack of data that support its use.. · We demonstrated a wide range of practice patterns in the weaning strategy of diuretics in outpatients' BPDs.. · Pulmonologists and neonatologists differ significantly in their weaning strategy.. · Most participants are unsatisfied with the existing data and guidelines regarding these issues..

Eosinophil cell count in bronchoalveolar lavage fluid in early childhood wheezing: is it predictive of future asthma?

Objective: Increased eosinophil level in bronchoalveolar lavage fluid (BALF) characterizes asthma in school-age children and adults and has been suggested as a marker for disease severity and response to treatment. We aimed to investigate the occurrence and yield of BALF eosinophil cell count in preschool children with recurrent wheezing and its possible relation to future diagnosis of asthma. Methods: BALF was retrospectively studied in young wheezy children and its relation to asthma at age 6 years was evaluated. BALF from children aged 1-48 months (mean = 20.4) was analyzed in preschool wheezy children. Children with anatomical airway obstruction and other lower airway/lung diseases who underwent BALF served as controls. Assessment of asthma was accomplished at 6 years. Results: Eighty-two children were included. The mean age during bronchoscopy and BAL was 20.4 ± 14.4 months (range: 1-48 months). Twenty-six patients had recurrent preschool wheezing, 13 anatomical airway obstruction and 43 had other lower airways/lung diseases. Groups were comparable for age during bronchoscopy and gender. No difference was found between groups for any of the BALF cell types. Eosinophils were very low in all three groups [mean (interquartile range): 0 (0-0.4), 0 (0-0.8), and 0.4 (0-1), respectively, p = 0.25]. No difference in eosinophil levels during bronchoscopy was found between asthmatic children to non-asthmatic as defined at age 6 years. Conclusions: Wheezing in preschool children is not associated with increased BALF eosinophils; hence, at this age, the diagnostic yield of BALF for cell count analysis for diagnosing asthma is limited and is not routinely indicated.

An International Survey Comparing Different Physician Models for Health Care Delivery to Critically Ill Children With Heart Disease.

OBJECTIVES: To explore relationships between the training background of cardiac critical care attending physicians and self-reported perceived strengths and weaknesses in their ability to provide clinical care. DESIGN: Cross-sectional observational survey sent worldwide to ~550 practicing cardiac ICU attending physicians. SETTING: Hospitals providing cardiac critical care. SUBJECTS: Practicing cardiac critical care physicians. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We received responses from 243 ICU attending physicians from 82 centers (14 countries). The primary training background of the respondents included critical care (62%), dual training in critical care and cardiology (16%), cardiology (14%), and other (8%). We received 49 responses from medical directors in nine countries, who reported that the predominant training background for attending physicians who provide cardiac intensive care at their institutions were critical care (58%), dual trained (18%), cardiology (12%), and other (11%). A greater proportion of physicians trained in either critical care or dual-training reported feeling confident managing multiple organ failure, neurologic conditions, brain death, cardiac arrest, and performing procedures like advanced airway placement and inserting chest- and abdominal-drains. In contrast, physicians with cardiology and dual-training reported feeling more confident managing intractable arrhythmias, understanding cardiopulmonary interactions, and interpreting echocardiogram, electrocardiogram, and cardiac catheterization. Overall, only 57% of the respondents felt comfortable based on their current training background to manage patients with complex cardiac issues without collaboration with other specialists. CONCLUSIONS: Our survey demonstrates that intensivists trained in critical care are more comfortable with critical care skills, cardiology-trained intensivists are more comfortable with cardiology skills, and dual-trained physicians are comfortable with both critical care skills and cardiology skills. These findings may help inform future efforts to optimize the educational curriculum and training pathways for future cardiac intensivists. These data may also be used to shape continuing medical education activities for cardiac intensivists who have already completed their training.

Predictors for hospital admission of asymptomatic to moderately symptomatic children after drowning.

Drowning is a leading cause of injury-related death worldwide, but there are limited data on the management and disposition of asymptomatic and mildly symptomatic adults and children following a drowning event. Some authors have recommended admission for all drowning victims due to the possibility of respiratory and clinical deterioration in a seemingly well patient. In order to identify predictors for admission and to establish a unified approach for management, we retrospectively collected all children ≤ 16 years old presented following a drowning event to the pediatric ED over a period of 12 years. The children were divided into two groups, those who were discharged home from the ED and those who were admitted. Seventy-one surviving and non-intubated children were asymptomatic to moderately symptomatic, and they comprised the study group. Crepitations on lung auscultation, oxygen desaturation, and respiratory distress were significantly higher in the admitted group (n = 26) compared with the discharged group (n = 45) (P < 0.05). Respiratory distress and lung crepitations were independent predictors for admission. Eventually, 30% of the hospitalized patients required oxygen therapy, but there were no cases that deteriorated and required invasive ventilation. No readmissions occurred in the group of children who were discharged from the ED.Conclusion: Children who after six hours show no respiratory distress and have normal oxygen saturation and normal auscultation can be safely discharged home. Respiratory distress and lung crepitations should both warrant the physician to consider admission of asymptomatic to moderately symptomatic children following a drowning event. An algorithm to assist patient management is proposed. What is Known: •There are few data in the literature regarding the management and disposition of asymptomatic to moderately symptomatic children after drowning. What is New: •We found that respiratory distress and lung crepitations are independent predictors for admission. An algorithm to assist patient management is proposed.

The value of cerebrospinal fluid lactate levels in diagnosing CSF infections in pediatric neurosurgical patients.

PURPOSE: Diagnosis of cerebrospinal fluid (CSF) infections in patients following neurosurgical procedures can be challenging. CSF lactate (LCSF) has been shown to assist in differentiating bacterial from non-bacterial meningitis in non-neurosurgical patients. The use of lactate in diagnosing CSF-related infections following neurosurgical procedures has been described in adults. The goal of this study was to describe the role of LCSF levels in diagnosing CSF-related infections among neurosurgical children. METHODS: We retrospectively collected data for all pediatric patients treated at a large tertiary pediatric neurosurgical department, for whom CSF samples were collected over a 2-year period. Lactate levels were correlated with other CSF parameters, surgical parameters, presence of CSF infection, and source of CSF sample (lumbar, ventricular, or pseudomeningocele). RESULTS: A total of 215 CSF samples from 162 patients were analyzed. We found a correlation between lactate levels and other CSF parameters. Lactate levels displayed an inconsistent correlation with infection depending on sample origin. Irrespective of the CSF source, lactate levels could not sufficiently discriminate between those with or without infection. Lactate levels were correlated with recent surgery, and, in some of the subgroups, to the extent of blood in CSF. CONCLUSIONS: LCSF levels are influenced by many factors, including the source of sample, recent surgery, and the presence of subarachnoid or ventricular blood secondary to surgery. The added value of LCSF for diagnosing CSF infections in children with a history of neurosurgical procedures is unclear and may be influenced by the extent of blood in the CSF.

Significant correlation between peripheral blood CD34+ cell count in children prior to aphaeresis and CD34+ cell yield following aphaeresis: A single-center experience.

Numerous adults' studies demonstrated that preaphaeresis CD34+ cells significantly correlate with the number of CD34+ cells collected by the aphaeresis procedure. Equivalent studies in children are scarce. We studied retrospectively 92 aphaeresis procedures performed following chemotherapy (44) or in steady state (48) in 60 pediatric patients (40 males, 20 females), median age of 7.5 years. Aphaeresis procedures were performed using a SPECTRA Optica (TERUMOBCT) continuous flow cell separator. CD34+ cell concentrations were assessed using flow cytometry. A highly significant correlation between peripheral CD34 cell count on the day of aphaeresis and CD34 cell yield per kg (R2  = .824, P < .0001) was demonstrated. A higher preaphaeresis CD34 cell count was demonstrated in patients with higher preaphaeresis white blood cell count, in patients with brain tumors, and in patients who received chemotherapy as part of their mobilization protocol. A threshold number of 20 peripheral CD34+ cell/µL was found to predict harvesting of 3 × 106 stem cells/kg, and 30 peripheral CD34+ cell/µL for harvesting of 5 × 106 stem cells/kg. This significant correlation between peripheral CD34 cell count and CD34 cell yield, and the threshold number of peripheral CD34 found to predict adequate harvesting can be useful in planning the optimal time for aphaeresis in children.

Neuroleptic Malignant Syndrome Associated With Metoclopramide Use in a Boy: Case Report and Review of the Literature.

Neuroleptic malignant syndrome (NMS), an idiosyncratic reaction comprising muscular rigidity, altered level of consciousness, and autonomic dysfunction, is a rare but serious medical condition. It is most commonly precipitated by major tranquilizers such as butyrophenones, phenothiazines, and thioxanthines. Metoclopramide, a chlorbenzamide derivative with antidopaminergic properties, is widely used to treat nausea and emesis. We describe the first reported case of a boy who developed NMS in association with the use of this drug. A 13-year-old boy presented to the emergency department with a history of hyperthermia (42.6°C) and altered level of consciousness. He had recently had acute gastroenteritis and had been treated with metoclopramide 10 mg three times a day for 2 days. Vital signs were notable for hypotension, and physical examination revealed altered mental status with muscle rigidity. Laboratory testing revealed metabolic acidosis and increased prothrombin and partial thromboplastin times. He was actively cooled and received 3 rapid boluses, totaling 60 mL/kg, of isotonic crystalloids, for more than 20 minutes. Sepsis workup revealed no evidence of bacterial infection. He subsequently recovered fully and was discharged home with pediatric follow-up. This case represents the first description of NMS in association with metoclopramide in a healthy boy. It demonstrates the importance of considering this diagnosis early in the course of disease in patients with muscular rigidity, altered level of consciousness and autonomic dysfunction, and the need to rapidly respond to the physiological aberrations.

Combined plerixafor and granulocyte colony-stimulating factor for harvesting high-dose hematopoietic stem cells: Possible niche for plerixafor use in pediatric patients.

PB is a source of HSC, especially for autologous HCT in solid tumors. However, there is a risk of failing to achieve the target number of SC after mobilization with growth factors alone in patients who were heavily pretreated with chemotherapy or those in need for tandem transplants. SC were harvested from seven pediatric patients with solid tumors who were in need of autologous HCT following combination GCSF and plerixafor. Six of them received plerixafor after failing to achieve enough SC with GCSF only, while the seventh patient received the combined protocol upfront. All seven patients achieved the target number of SC according to their treatment protocol. There were no adverse events. All patients underwent autologous HCT using the harvested HSC and achieved full engraftment. A protocol for harvesting autologous HCT using GCSF and plerixafor is feasible and safe in children with solid tumors who had been heavily pretreated with chemotherapy or needed tandem transplants.

Asthma risk after a pediatric intensive care unit admission for respiratory syncytial virus bronchiolitis.

BACKGROUND: Admission to a pediatric intensive care unit (PICU) has been associated with respiratory consequences in children with asthma and carries major implications for management control. Whereas respiratory syncytial virus (RSV) bronchiolitis has been associated with increasing intensity of wheezing, the relationship between RSV-bronchiolitis PICU admission and future asthma is unclear. This retrospective case-control study evaluated whether hospitalization in the PICU due to RSV bronchiolitis is more likely to be associated with future asthma in early life compared with hospitalization in a general pediatric ward. METHODS: Children hospitalized due to RSV bronchiolitis between 2007 and 2019 in the PICU (study group) were compared to those hospitalized in a general pediatric ward (controls). Asthma prevalence was assessed by a follow-up questionnaire based on The International Study of Asthma and Allergies in Childhood questionnaire. RESULTS: Sixty-three PICU patients and 66 controls were included. The PICU patients presented with more severe disease during RSV hospitalization. At follow-up, significantly more PICU patients aged 3-6 years had physician-diagnosed asthma, respiratory symptoms during the previous 12 months, and underwent respiratory treatment since hospital discharge compared to controls (14 [60.9%] vs. 4 [18.2%] patients; 15 [65.2%] vs. 6 [27.3%]; and 16 [69.6%] vs. 8 [36.4%]; respectively). These differences were no longer observed after 6 years of age. CONCLUSIONS: Children admitted to the PICU for RSV bronchiolitis are at higher risk for asthma in subsequent pre-school years and will require close respiratory follow-up than those admitted to general pediatric wards. Admission venue should be queried when asthma is suspected.

Nonrespiratory complications of nusinersen-treated spinal muscular atrophy type 1 patients.

BACKGROUND: Emergence of new treatments for spinal muscular atrophy type 1 (SMA1) has led to dramatic improvements in respiratory failure and survival. However, these "treated" patients sustain major problems in other organ systems, which may directly or indirectly affect their respiratory function. We observed three main nonrespiratory manifestations in these patients comprised of facial deformities, feeding problems, and spinal deformities. OBJECTIVE: To investigate these three main sequelae in nusinersen-treated SMA1 patients. METHODS: Data on nusinersen-treated SMA1 patients were prospectively collected throughout a 3-year period, with special focus upon nonrespiratory features of the disease. RESULTS: Twenty nusinersen-treated SMA1 patients were included (eight males, median age 13.5 months, interquartile range: 4-56.2 months), among whom 17 survived after 3 years of follow-up. At follow-up, 15 (88%) patients were diagnosed with facial weakness, hypoplasia, or deformity. All but one patient (94%) were fed invasively by percutaneous endoscopic gastrostomy or nasogastric tube feeding. Four patients (25%) had maintained oral feeding in parallel to gastrostomy feeding and had clinical and radiologic evidence of aspirations. Fifteen (88%) patients were diagnosed with scoliosis, of whom seven had undergone or were scheduled to undergo corrective surgery. CONCLUSIONS: Nusinersen-treated SMA1 patients may sustain facial deformities, feeding problems, and severe scoliosis, all of which affect their respiratory system. Strict surveillance of these complications is essential to avoid further respiratory morbidity.

Prolonged mechanical support in children with severe adenoviral infections: a case series and review of the literature.

Adenovirus infections occur primarily in infants and children less than 5 years of age, accounting for 2% to 5% of respiratory illnesses in the pediatric population and 4% to 10% of childhood pneumonias. Although the majority of children with adenovirus disease develop mild upper respiratory tract disease, more severe disease may occur with involvement of the lower respiratory tract characterized by pneumonitis and/or small airways disease. The authors present a case series of 3 high-risk children with severe lower respiratory tract adenoviral infections. These cases demonstrate the potential for the development of severe respiratory involvement from adenovirus in infants and children with comorbid conditions and illustrate that there may be a rapid progression of the disease as well as the need, in selected circumstances, for prolonged mechanical support. We review the role of adenovirus in lower respiratory tract infections in infants and children, its potential to result in life-threatening complications in pediatric patients with comorbid conditions, and the potential life-saving role of mechanical ventilation and extracorporeal life support (ECLS) in these children.

Nusinersen for spinal muscular atrophy type 1: Real-world respiratory experience.

BACKGROUND: The emergence of new treatments for spinal muscular atrophy (SMA) is revolutionary, especially for SMA type 1 (SMA1). Data on respiratory outcomes remain sparse and rely mostly on randomized clinical trials. We report our experience of Nusinersen-treated SMA1 patients in real-world settings. METHODS: Data from SMA1 patients treated with Nusinersen were prospectively collected between 1/2017 and 1/2020. Respiratory variables included the use of assisted ventilation, the use of mechanical insufflation-exsufflation (MIE), respiratory complications, and death or treatment cessation due to respiratory reasons. RESULTS: Twenty SMA1 patients were assessed before and after 2 years of Nusinersen treatment which was initiated at a median age of 13.5 months (range, 1-184). At baseline, 16 patients were using assisted ventilation, eight noninvasive and eight invasive. Twelve patients were using permanent ventilation and four partial ventilation. After 2 years of treatment, there was no change in respiratory support among ventilated patients. All four patients who were free from respiratory support at baseline required the initiation of assisted ventilation during the study period. All 20 patients used MIE after 2 years of treatment. Two patients died from acute respiratory failure and one sustained severe brain injury. Four patients had chronic and/or recurrent atelectasis. CONCLUSION: Most of our patients were stable in their need for assisted ventilation and did not worsen as expected in SMA1, nor did they improve as might be hoped. Future studies are needed to determine if earlier treatment with Nusinersen might result in respiratory outcomes superior to those reported in this real-life study.

High fractional exhaled nitric oxide levels in asthma patients: Does size matter?

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is a biomarker for eosinophilic inflammation used for diagnosis and monitoring of asthma. High FeNO indicates significant airway eosinophilia and steroid-responsive airway inflammation. Some children with asthma have extremely high FeNO levels, but whether these levels represent a different asthma phenotype compared with those with mildly elevated FeNO is unclear. The objective of this study is to investigate whether the extent of high FeNO levels correlates with clinical phenotype, asthma control, comorbidity, and pulmonary function test (PFT) findings in children with asthma. METHODS: Anthropometric data, daytime and nighttime symptoms, controller treatment, comorbidity, and PFT findings were retrieved from the Pediatric Pulmonology Unit database (2014-2020) and correlated with FeNO levels in pediatric asthma patients with high FeNO levels. RESULTS: Two-hundred children and adolescents with high FeNO levels (range 36-227 ppb) were included. Within this range, higher FeNO levels positively correlated with increased daytime and nighttime symptoms (p = .013 and p = .01, respectively) and poorly controlled asthma (p = .034). A FeNO level of ≥80 ppb was the cutoff for significantly more severe daytime and nighttime symptoms and very poorly controlled asthma compared with levels <80 ppb (p = .004, p = .005, and p = .036, respectively). No correlation was found between FeNO and controller treatment, comorbidity, and PFT performance. CONCLUSION: In pediatric asthma patients, high FeNO levels correlate with increased symptom severity and poor asthma control. A FeNO level of ≥80 ppb may serve as an objective indicator for severe asthma.

Variability of Care of Infants With Severe Respiratory Syncytial Virus Bronchiolitis: A Multicenter Study.

BACKGROUND: Viral bronchiolitis caused by respiratory syncytial virus (RSV) is a common childhood disease accounting for many hospitalizations worldwide. Some infants may clinically deteriorate, requiring admission to an intensive care unit. We aimed to describe diagnostic and therapeutic measures of bronchiolitis in Israeli pediatric intensive care units (PICUs) and evaluate intercenter variability of care. METHODS: Medical records of all RSV-infected infants admitted to 5 Israeli PICUs over 4 RSV seasons were retrospectively reviewed. RESULTS: Data on 276 infants with RSV-positive bronchiolitis, admitted to the participating PICUs were analyzed. Most of the infants were males with a mean admission age of 4.7 months. Approximately half of the infants had pre-existing conditions such as prematurity, cardiac disease or chronic lung disease. Respiratory distress was the most common symptom at presentation followed by hypoxemia and fever. There was significant variation in the methods used for RSV diagnosis, medical management and respiratory support of the infants. Furthermore, utilization of inhalational therapy and transfusion of blood products differed significantly between the centers. Although a bacterial pathogen was isolated in only 13.4% of the infants, 82.6% of the cohort was treated with antibiotics. CONCLUSIONS: Significant variation was found between the different PICUs regarding RSV bronchiolitis diagnosis, medical management and respiratory support, which may not be accounted for by the differences in baseline and clinical characteristics of the infants. Some of these differences may be explained by uneven resource allocations. This diversity and the documented routine use of medications with weak evidence of efficacy calls for national guidelines for bronchiolitis management.

Isavuconazole As Successful Salvage Therapy for Mucormycosis in Pediatric Patients.

BACKGROUND: Mucormycosis is a rare but emerging life-threatening fungal disease with limited treatment options. Isavuconazole is a new triazole that has shown efficacy in adults for primary and salvage treatment of mucormycosis. However, data in children are scarce. METHODS: The demographic and clinical data of pediatric patients with proven mucormycosis who were treated with isavuconazole in 2015 to 2019 at 2 centers were collected. RESULTS: Four children of median age 10.5 years (range 7-14) met the study criteria. Three had underlying hematologic malignancies, and 1 had sustained major trauma. Isavuconazole was used as salvage therapy in all: in 3 patients for refractory disease, and in 1 after intolerance to another antifungal drug. Isavuconazole was administered alone or combined with other antifungal agents. Following treatment and surgical intervention, complete clinical, radiologic and mycologic responses were documented in all patients. A literature review identified 8 children with mucormycosis who were successfully treated with isavuconazole, as salvage therapy in the majority. CONCLUSION: Our limited experience supports the use of isavuconazole as salvage therapy in pediatric mucormycosis.

A Case of Methotrexate Neurotoxicity Presented as Status Epilepticus, Encephalopathy, and High Fever.

High-dose methotrexate is used to treat a range of adult and childhood cancers including osteosarcoma. Significant neurotoxicity is reported in 1% to 4.5% of patients treated with high-dose methotrexate and can present in a wide variety of symptoms. We present a case of a 14-year-old boy with a recent diagnosis of osteosarcoma who presented to the emergency department with status epilepticus, altered mental status, and very high fever secondary to methotrexate neurotoxicity. We review current literature and discuss some controversies related to this state. We also describe high fever as one of the possible symptoms associated with this condition and suggest using specific magnetic resonance imaging sequence to uncover abnormal findings related to this state. Since high-dose methotrexate is not a rare treatment in this era, we believe that in addition to oncologists, emergency department and intensive care providers should be aware of the potential role of methotrexate in causing significant neurotoxicity and include it in the differential diagnosis when treating a patient presenting with new neurological symptoms in the setting of recent high-dose methotrexate treatment.

Value of Cerebrospinal Fluid Lactate Levels in Diagnosing Shunt Infections in Pediatric Patients.

OBJECTIVE: The diagnosis and timely treatment of shunt infections (SI) in children is of paramount importance. In some cases, the standard cerebrospinal fluid (CSF) variables will not be sufficient for an accurate diagnosis of SI. CSF lactate (LCSF) has been found to assist in differentiating bacterial from nonbacterial meningitis in non-neurosurgical patients. To the best of our knowledge, the use of lactate in diagnosing or confirming the presence of SI has not yet been discussed. The goal of the present study was to describe the role of LCSF levels in children with shunts and Ommaya reservoirs and to evaluate its role in the accurate diagnosis of shunt-related infection. METHODS: We retrospectively collected data for a consecutive series of pediatric patients treated at a large tertiary pediatric neurosurgical department, for whom CSF samples from shunts had been collected during a 2-year period (2016-2017). The lactate levels were correlated with the presence of SI. RESULTS: A total of 61 CSF samples were analyzed, with 6 SIs found. The LCSF levels and white blood cell count were both found to correlate with the presence of CSF infections. A cutoff value of ≥2.95 mmol/L reached a sensitivity of 83%, specificity of 83%, and positive predictive value of 50%. LCSF <2.95 mmol/L had a negative predictive value of 96%. CONCLUSIONS: LCSF levels can be used as an additional chemical marker for the diagnosis and confirmation of SIs. An LCSF value of <2.95 mmol/L had a high negative predictive value.

Laryngeal ultrasound for the diagnosis of laryngomalacia in infants.

INTRODUCTION: Laryngomalacia is the most prevalent cause of congenital stridor. Flexible laryngobronchoscopy (FLB) is the gold standard for diagnosis. However, FLB requires venous access, deep sedation or general anesthesia, and is associated with patient's and parental discomfort and a considerable cost. Laryngeal ultrasound (LUS) has been shown to provide good evaluation of the normal anatomy and the dynamic motion of laryngeal structures. We investigated the yield of LUS in the diagnosis of laryngomalacia in infants with congenital stridor compared to FLB. METHODS: A prospective blind study of consecutive infants referred for FLB due to congenital stridor with unknown cause. The presence of arytenoids adduction on LUS during inspiration was used to diagnose laryngomalacia. LUS was followed by FLB under anesthesia. The physician performing the FLB was blinded to the LUS results. RESULTS: Twenty-four patients participated in the study (54% males). Median (IQR) age and weight were 3.5 (1-7.7) months and 5.1 (4-8.4) kg, respectively. LUS was well tolerated in all infants. Compared to FLB, LUS correctly diagnosed laryngomalacia in 11/14 (78.6%) infants. In 10 infants FLB ruled out laryngomalacia of whom LUS concurred in 9 infants and one was falsely diagnosed with laryngomalacia. LUS had a sensitivity of 78.5% (CI 52-95%), specificity of 90% (CI 49-94%), NPV of 75%, and PPV of 92%. ROC analysis demonstrated AUC of 0.84 (P < 0.01, 95%CI: 0.67-1.0). CONCLUSION: We suggest that LUS has a role in screening congenital stridor in otherwise healthy infants when laryngomalacia is highly probable.