Evaluating Airway Management in Patients With Trisomy 21 in the PICU and Cardiac ICU: A Retrospective Cohort Study.

OBJECTIVES: Children with trisomy 21 often have anatomic and physiologic features that may complicate tracheal intubation (TI). TI in critically ill children with trisomy 21 is not well described. We hypothesize that in children with trisomy 21, TI is associated with greater odds of adverse airway outcomes (AAOs), including TI-associated events (TIAEs), and peri-intubation hypoxemia (defined as > 20% decrease in pulse oximetry saturation [Sp o2 ]). DESIGN: Retrospective database study using the National Emergency Airway Registry for Children (NEAR4KIDS). SETTING: Registry data from 16 North American PICUs and cardiac ICUs (CICUs), from January 2014 to December 2020. PATIENTS: A cohort of children under 18 years old who underwent TI in the PICU or CICU from in a NEAR4KIDS center. We identified patients with trisomy 21 and selected matched cohorts within the registry. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 8401 TIs in the registry dataset. Children with trisomy 21 accounted for 274 (3.3%) TIs. Among those with trisomy 21, 84% had congenital heart disease and 4% had atlantoaxial instability. Cervical spine protection was used in 6%. The diagnosis of trisomy 21 (vs. without) was associated with lower median weight 7.8 (interquartile range [IQR] 4.5-14.7) kg versus 10.6 (IQR 5.2-25) kg ( p < 0.001), and more higher percentage undergoing TI for oxygenation (46% vs. 32%, p < 0.001) and ventilation failure (41% vs. 35%, p = 0.04). Trisomy 21 patients had more difficult airway features (35% vs. 25%, p = 0.001), including upper airway obstruction (14% vs. 8%, p = 0.001). In addition, a greater percentage of trisomy 21 patients received atropine (34% vs. 26%, p = 0.004); and, lower percentage were intubated with video laryngoscopy (30% vs. 37%, p = 0.023). After 1:10 (trisomy 21:controls) propensity-score matching, we failed to identify an association difference in AAO rates (absolute risk difference -0.6% [95% CI -6.1 to 4.9], p = 0.822). CONCLUSIONS: Despite differences in airway risks and TI approaches, we have not identified an association between the diagnosis of trisomy 21 and higher AAOs.

Adverse Tracheal Intubation Events in Critically Ill Underweight and Obese Children: Retrospective Study of the National Emergency Airway for Children Registry (2013-2020).

OBJECTIVES: Extremes of patient body mass index are associated with difficult intubation and increased morbidity in adults. We aimed to determine the association between being underweight or obese with adverse airway outcomes, including adverse tracheal intubation (TI)-associated events (TIAEs) and/or severe peri-intubation hypoxemia (pulse oximetry oxygen saturation < 80%) in critically ill children. DESIGN/SETTING: Retrospective cohort using the National Emergency Airway for Children registry dataset of 2013-2020. PATIENTS: Critically ill children, 0 to 17 years old, undergoing TI in PICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Registry data from 24,342 patients who underwent TI between 2013 and 2020 were analyzed. Patients were categorized using the Centers for Disease Control and Prevention weight-for-age chart: normal weight (5th-84th percentile) 57.1%, underweight (< 5th percentile) 27.5%, overweight (85th to < 95th percentile) 7.2%, and obese (≥ 95th percentile) 8.2%. Underweight was most common in infants (34%); obesity was most common in children older than 8 years old (15.1%). Underweight patients more often had oxygenation and ventilation failure (34.0%, 36.2%, respectively) as the indication for TI and a history of difficult airway (16.7%). Apneic oxygenation was used more often in overweight and obese patients (19.1%, 19.6%) than in underweight or normal weight patients (14.1%, 17.1%; p < 0.001). TIAEs and/or hypoxemia occurred more often in underweight (27.1%) and obese (24.3%) patients ( p < 0.001). TI in underweight children was associated with greater odds of adverse airway outcome compared with normal weight children after adjusting for potential confounders (underweight: adjusted odds ratio [aOR], 1.09; 95% CI, 1.01-1.18; p = 0.016). Both underweight and obesity were associated with hypoxemia after adjusting for covariates and site clustering (underweight: aOR, 1.11; 95% CI, 1.02-1.21; p = 0.01 and obesity: aOR, 1.22; 95% CI, 1.07-1.39; p = 0.002). CONCLUSIONS: In underweight and obese children compared with normal weight children, procedures around the timing of TI are associated with greater odds of adverse airway events.

Treatment of comatose patient from cyclobenzaprine overdose with therapeutic plasma exchange.

We present a case of a 15-year-old female who was admitted in a comatose state with no spontaneous respiratory effort and absence of brainstem reflexes after cyclobenzaprine ingestion. Due to severe presentation and recent ingestion of high plasma protein binding medication with long half-life, therapeutic plasma exchange (TPE) was performed and resulted in full neurological recovery. This case explores the role of TPE as an effective treatment option for life-threatening cyclobenzaprine overdose. TPE is generally beneficial for drugs that have a low volume of distribution and high plasma protein binding. Cyclobenzaprine is known to have a relatively high volume of distribution. However, in the case of drug intoxication with relatively high-volume distribution, high protein binding, and long half-life, TPE could be effective if it is conducted promptly.

Deficiency in ST2 signaling ameliorates RSV-associated pulmonary hypertension.

Pulmonary hypertension (PH) observed during respiratory syncytial virus (RSV) bronchiolitis is associated with morbidity and mortality, especially in children with congenital heart disease. Yet, the pathophysiological mechanisms of RSV-associated PH remain unclear. Therefore, this study aimed to investigate the pathophysiological mechanism of RSV-associated PH. We used a translational mouse model of RSV-associated PH, in which wild-type (WT) and suppression of tumorigenicity 2 (ST2) knockout neonatal mice were infected with RSV at 5 days old and reinfected 4 wk later. The development of PH in WT mice following RSV reinfection was evidenced by elevated right ventricle systolic pressure, shortened pulmonary artery acceleration time (PAT), and decreased PAT/ejection time (ET) ratio. It coincided with the augmentation of periostin and IL-13 expression and increased arginase bioactivity by both arginase 1 and 2 as well as induction of nitric oxide synthase (NOS) uncoupling. Absence of ST2 signaling prevented RSV-reinfected mice from developing PH by suppressing NOS uncoupling. In summary, ST2 signaling was involved in the development of RSV-associated PH. ST2 signaling inhibition may be a novel therapeutic target for RSV-associated PH.NEW & NOTEWORTHY We report that the pathogenic role of ST2-mediated type 2 immunity and mechanisms contribute to RSV-associated pulmonary hypertension. Inhibiting ST2 signaling may be a novel therapeutic target for this condition.

Pulmonary hypertension during respiratory syncytial virus bronchiolitis: a risk factor for severity of illness.

BACKGROUND: Respiratory syncytial virus infection is the most frequent cause of acute lower respiratory tract disease in infants. A few reports have suggested that pulmonary hypertension is associated with increased severity of respiratory syncytial virus infection. We sought to determine the association between the pulmonary hypertension detected by echocardiography during respiratory syncytial virus bronchiolitis and clinical outcomes. METHODS: We retrospectively reviewed 154 children admitted with respiratory syncytial virus bronchiolitis who had an echocardiography performed during the admission. The association between pulmonary hypertension and clinical outcomes including mortality, intensive care unit (ICU) admission, prolonged ICU stay (>10 days), tracheal intubation, and need of high frequency oscillator ventilation was evaluated. RESULTS: Echocardiography detected pulmonary hypertension in 29 patients (18.7%). Pulmonary hypertension was observed more frequently in patients with congenital heart disease (CHD) (n = 11/33, 33%), chronic lung disease of infancy (n = 12/25, 48%), prematurity (<37 weeks gestational age, n = 17/59, 29%), and Down syndrome (n = 4/10, 40%). The presence of pulmonary hypertension was associated with morbidity (p < 0.001) and mortality (p = 0.02). However, in patients without these risk factors (n = 68), pulmonary hypertension was detected in five patients who presented with shock or poor perfusion. Chronic lung disease was associated with pulmonary hypertension (OR = 5.9, 95% CI 2.2-16.3, p = 0.0005). Multivariate logistic analysis demonstrated that pulmonary hypertension is associated with ICU admission (OR = 6.4, 95% CI 2.2-18.8, p = 0.0007), intubation (OR = 4.7, 95% CI 1.8-12.3, p = 0.002), high frequency oscillator ventilation (OR = 8.4, 95% CI 2.95-23.98, p < 0.0001), and prolonged ICU stay (OR = 4.9, 95% CI 2.0-11.7, p = 0.0004). CONCLUSIONS: Pulmonary hypertension detected by echocardiography during respiratory syncytial virus infection was associated with increased morbidity and mortality. Chronic lung disease was associated with pulmonary hypertension detected during respiratory syncytial virus bronchiolitis. Routine echocardiography is not warranted for previously healthy, haemodynamically stable patients with respiratory syncytial virus bronchiolitis.

New mouse model of pulmonary hypertension induced by respiratory syncytial virus bronchiolitis.

Pulmonary hypertension (PH) has been observed in up to 75% of infants with moderate to severe respiratory syncytial virus (RSV) bronchiolitis and is associated with significant morbidity and mortality in infants with congenital heart disease. The purpose of the present study was to establish a mouse model of PH secondary to RSV bronchiolitis that mimics the disease etiology as it occurs in infants. Neonatal mice were infected with RSV at 5 days of age and then reinfected 4 wk later. Serum-free medium was administered to age-matched mice as a control. Echocardiography and right ventricular systolic pressure (RVSP) measurements via right jugular vein catheterization were conducted 5 and 6 days after the second infection, respectively. Peripheral capillary oxygen saturation monitoring did not indicate hypoxia at 2-4 days post-RSV infection, before reinfection, and at 2-7 days after reinfection. RSV-infected mice had significantly higher RVSP than control mice. Pulsed-wave Doppler recording of the pulmonary blood flow by echocardiogram demonstrated a significantly shortened pulmonary artery acceleration time and decreased pulmonary artery acceleration time-to-ejection time ratio in RSV-infected mice. Morphometry showed that RSV-infected mice exhibited a significantly higher pulmonary artery medial wall thickness and had an increased number of muscularized pulmonary arteries compared with control mice. These findings, confirmed by RVSP measurements, demonstrate the development of PH in the lungs of mice infected with RSV as neonates. This animal model can be used to study the pathogenesis of PH secondary to RSV bronchiolitis and to assess the effect of treatment interventions. NEW & NOTEWORTHY This is the first mouse model of respiratory syncytial virus-induced pulmonary hypertension, to our knowledge. This model will allow us to decipher molecular mechanisms responsible for the pathogenesis of pulmonary hypertension secondary to respiratory syncytial virus bronchiolitis with the use of knockout and/or transgenic animals and to monitor therapeutic effects with echocardiography.

Regulation of inflammatory biomarkers by intravenous methylprednisolone in pediatric ARDS patients: Results from a double-blind, placebo-controlled randomized pilot trial.

OBJECTIVE: A double-blind, randomized controlled trial showed that low-dose glucocorticoid therapy in pediatric ARDS patients is feasible and may improve both ventilation and oxygenation indices in these patients. However, the molecular mechanisms underlying potential changes in outcomes remain unclear. Based on these clinical findings, this study was designed to examine the effects of intravenous methylprednisolone on circulating inflammatory biomarkers in pediatric ARDS patients. DESIGN: Double-blind, placebo-controlled randomized trial with blood collection on study entry and day 7. SETTING: Tertiary care children's hospital. PATIENTS: Children (0-18years) with ARDS undergoing mechanical ventilation. INTERVENTIONS: 35 children were randomized within 72h of mechanical ventilation. The glucocorticoid group received methylprednisolone 2mg/kg loading dose followed by 1mg/kg/day continuous infusion from days 1 to 7. Both groups were ventilated following the ARDSnet recommendations. WBC and differential cell counts, plasma cytokines and CRP levels, and coagulation parameters were analyzed on days 0 and 7. RESULTS: At study entry, the placebo group had higher IL-15 and basophil levels. On day 7, in comparison to study entry, the placebo group had lower IL-1α, IFN-γ and IL-10 levels. The glucocorticoid group had lower INF-α, IL-6, IL-10, MCP-1, G-CSF and GM-CSF levels, and higher IL-17α levels on day 7 in comparison to study entry. Total and differential cell counts remained unchanged within the placebo group between days 0 and 7, whereas in the glucocorticoid group total WBC and platelets counts were increased on day 7. Pearson's correlation studies within the placebo and glucocorticoid groups revealed positive and negative correlations between cytokine levels, cell counts, coagulation parameters and relevant clinical parameters of disease severity identified in our previous study. Multiple regression models identified several cytokines as predictors for alterations in clinical parameters of disease severity. CONCLUSION: This pilot study shows the feasibility of simultaneously measuring multiple inflammatory cytokines, cell counts and coagulation parameters in pediatric ARDS patients. We report statistical models that may be useful for future, larger trials to predict ARDS severity and outcomes.

Double-blind, placebo-controlled pilot randomized trial of methylprednisolone infusion in pediatric acute respiratory distress syndrome.

OBJECTIVE: Low-dose methylprednisolone therapy in adults with early acute respiratory distress syndrome reduces systemic inflammation, duration of mechanical ventilation, and ICU length of stay. We report a pilot randomized trial of glucocorticoid treatment in early pediatric acute respiratory distress syndrome. DESIGN: Double-blind, placebo-controlled randomized clinical trial. SETTING: Le Bonheur Children's Hospital, Memphis, TN. PATIENTS: Children (0-18 yr) with acute respiratory distress syndrome undergoing mechanical ventilation. INTERVENTIONS: Patients were randomly assigned to steroid or placebo groups within 72 hours of intubation. IV methylprednisolone administered as loading dose (2 mg/kg) and continuous infusions (1 mg/kg/d) on days 1-7 and then tapered over days 8-14. Both groups were ventilated according to the Acute Respiratory Distress Syndrome Network protocol modified for children. Daily surveillance was performed for adverse effects. MEASUREMENTS AND MAIN RESULTS: Thirty-five patients were randomized to the steroid (n = 17, no death) and placebo groups (n = 18, two deaths). No differences occurred in length of mechanical ventilation, ICU stay, hospital stay, or mortality between the two groups. At baseline, higher plateau pressures (p = 0.006) and lower Pediatric Logistic Organ Dysfunction scores (p = 0.04) occurred in the steroid group; other characteristics were similar. Despite higher plateau pressures on days 1 (p = 0.006) and 2 (p = 0.025) due to poorer lung compliance in the steroid group, they had lower PaCO2 values on days 2 (p = 0.009) and 3 (p = 0.014), higher pH values on day 2 (p = 0.018), and higher PaO2/FIO2 ratios on days 8 (p = 0.047) and 9 (p = 0.002) compared with the placebo group. Fewer patients in the steroid group required treatment for postextubation stridor (p = 0.04) or supplemental oxygen at ICU transfer (p = 0.012). Steroid therapy was not associated with detectable adverse effects. CONCLUSION: This study demonstrates the feasibility of administering low-dose glucocorticoid therapy and measuring clinically relevant outcomes in pediatric acute respiratory distress syndrome. Changes in oxygenation and/or ventilation are consistent with early acute respiratory distress syndrome pathophysiology and results of similar clinical trials in adults. We propose and design a larger randomized trial to define the role of glucocorticoid therapy in pediatric acute respiratory distress syndrome.

An adult right inguinal hernia and cryptorchidism treated simultaneously with laparoscopic transabdominal preperitoneal repair and laparoscopic orchiectomy: a case report.

Pediatric health checkups have been mandatory for all citizens since 1966 based on the Maternal and Child Health Law in Japan, and cryptorchidism or undescended testis in adult males are rare. We report a case of an adult right inguinal hernia and cryptorchidism treated simultaneously with laparoscopic transabdominal preperitoneal repair and laparoscopic orchiectomy. A 35-year-old man came to our department with a chief complaint of bulging in the right inguinal region for several months. He was diagnosed with a right inguinal hernia and was scheduled for transabdominal preperitoneal repair. During intraoperative intraperitoneal observation, a white 30-mm mass was found in the hernia orifice. A diagnosis of right cryptorchidism was made, and transabdominal preperitoneal repair and laparoscopic orchiectomy were performed. Laparoscopic simultaneous surgery could be safely performed in an adult patient with a hernia complicated by a cryptorchidism. It can be recommended as a surgical option in such cases.

Admission and treatment factors associated with the duration of acidosis in children with diabetic ketoacidosis.

BACKGROUND: Our goal was to determine the factors associated with prolonged acidosis in children with diabetic ketoacidosis. METHOD: The records of all children (109 admissions, 86 patients) admitted to the pediatric intensive care unit (PICU) during a 3-year period with the diagnosis of diabetic ketoacidosis were analyzed. RESULTS: The charts were reviewed after institutional review board approval was obtained. Demographic and serial laboratory data, time to correction of acidosis, as well as the first 24-hour chloride load, total fluid administered, fluid balance, and PICU and hospital lengths of stay were recorded. The anion gap (AG = Na - Cl - HCO(3)) and the delta gap (DG = AG - 12 - [24 - HCO(3)]) were calculated. Prolonged acidosis (HCO(3) < 15 mEq/L at 24 hours) was analyzed against various independent factors on admission and during therapy. Low Na (128 vs 133 mEq/L), HCO3 (4.7 vs 9.5 mEq/L), DG (-6.3 vs -2.8 mEq/L), pH (6.97 vs 7.16), PaCO(2) (15 vs 23 mm Hg), and base excess (-26 vs -18) as well as high chloride load (17 vs 11 mEq/kg per 24 hours) were associated with prolonged acidosis (t test, P < 0.05). Stepwise logistic regression eliminated all except base excess and DG in the model. Children with prolonged acidosis had longer PICU (45 vs 34 hours) and hospital stays (5.5 vs 2.5 days) (P < 0.05). The AG was normal in all cases at 24 hours. There were no deaths. CONCLUSIONS: Nongap acidosis was present in many children with prolonged metabolic acidosis. We suggest that a continuous acetate or bicarbonate therapy via maintenance fluid might be beneficial in this subgroup of patients.

Small-sized Pulmonary Adenocarcinoma Manifesting Skip-like Transition from Nonsolid Nodule: A Case Report.

This report shows a case with a rare small-sized lung adenocarcinoma that rapidly progressed from a nonsolid nodule (NSN) to a solid nodule (SON) over a period of just 1 year after a very long-term observation from its first detection. In 2007, the patient was an asymptomatic 52-year-old man at the time of the first detection via chest low-dose computed tomography (CT) screening as part of a periodic medical checkup at our hospital. It revealed an abnormal shadow in another location of the lung field, necessitating a more thorough examination. Then, he visited our outpatient clinic for the first time and a workup examination was performed using thin-section CT (TSCT) images, which incidentally detected a small NSN with a maximum diameter of 1.2 cm in the mid-zone of the left upper lung field. Since it did not disappear in the periodic subsequent workup examinations, the patient was informed of the suspicious early lung adenocarcinoma each time; however, the patient desired to continue watchful waiting. The radiographical properties of the NSN remained almost unchanged until 2019, but in 2020, the inside of the nodule showed a skip-like change to a SON. Finally, because of the unexpectedly fast transition, consent for lobectomy could be obtained. Surgery was then performed, 13 years after its first detection, at an age of 65 years. The pathological findings revealed a 1.2 cm, pT1bN0M0, pStage IA2-adenocarcinoma, which was 90% of the acinar subtype with positive vascular permeation. Management of a NSN, that does not resolve and/or change, must continue watchful waiting, and at the very least continue follow-up with TSCT observation to ensure the safe and appropriate timing of excision using imaging as a marker of transition.

Extramedullary hematopoiesis in gastric wall under early gastric cancer in a man with a myeloproliferative disorder: a case report.

Extramedullary hematopoiesis (EMH) is the proliferation of hematopoietic stem cells outside the bone marrow and often observed in the liver, spleen in association with myeloproliferative disorders. On the other hand, EMH in the gastric wall is extremely rare. We report a rare case of EMH foci coexisting with early gastric cancer, which resulted in severe gastrointestinal bleeding. A 70-year-old male was diagnosed with myelofibrosis 4 years ago and visited our emergency room with a complaint of hematemesis and tarry stools. Upper gastrointestinal endoscopy revealed three early-stage gastric cancers in the lower gastric body and antrum, and biopsy was performed. Persistent bleeding at the biopsy site of the hypogastric lesion led to the consideration of surgical intervention. An open distal gastrectomy was performed. Postoperative histopathological examination revealed the tumor of the lower gastric body had EMH foci associated with myelofibrosis.

Intubation practice and outcomes among pediatric emergency departments: A report from National Emergency Airway Registry for Children (NEAR4KIDS).

BACKGROUND: Tracheal intubation (TI) practice across pediatric emergency departments (EDs) has not been comprehensively reported. We aim to describe TI practice and outcomes in pediatric EDs in contrast to those in intensive are units (ICUs) and use the data to identify quality improvement targets. METHODS: Consecutive TI encounters from pediatric EDs and ICUs in the National Emergency Airway Registry for Children (NEAR4KIDS) database from 2015 to 2018 were analyzed for patient, provider, and practice characteristics and outcomes: adverse TI-associated events (TIAEs), oxygen desaturation (SpO2 < 80%), and procedural success. A multivariable model identified factors associated with TIAEs in the ED. RESULTS: A total of 756 TIs in 13 pediatric EDs and 12,512 TIs in 51 pediatric/cardiac ICUs were reported. Median (interquartile range [IQR]) patient age for ED TIs was higher (32 [7-108] months) than that for ICU TIs (15 [3-91] months; p < 0.001). Proportion of TIs for respiratory decompensation (52% of ED vs. 64% ICU), shock (26% vs. 14%), and neurologic deterioration (30% vs. 11%) also differed by location. Limited neck mobility was reported more often in the ED (16% vs. 6%). TIs in the ED were performed more often via video laryngoscopy (64% vs. 29%). Adverse TIAE rates (15.6% ED, 14% ICU; absolute difference = 1.6%, 95% confidence interval [CI] = -1.1 to 4.2; p = 0.23) and severe TIAE rates (5.4% ED, 5.8% ICU; absolute difference = -0.3%, 95% CI = -2.0 to 1.3; p = 0.68) were not different. Oxygen desaturation was less commonly reported in ED TIs (13.6%) than ICU TIs (17%, absolute difference = -3.4%, 95% CI = -5.9 to -0.8; p = 0.016). Among ED TIs, shock as an indication (adjusted odds ratio [aOR] = 2.15, 95% CI = 1.26 to 3.65) and limited mouth opening (aOR = 1.74, 95% CI = 1.04 to 2.93) were independently associated with TIAEs. CONCLUSIONS: While TI characteristics vary between pediatric EDs and ICUs, outcomes are similar. Shock and limited mouth opening were independently associated with adverse TI events in the ED.

Does hypercapnia ameliorate hyperoxia-induced lung injury in neonatal rats?

Therapeutic hypercapnia (TH), an intentional inhalation of CO(2), has been shown to improve pulmonary function in certain models of lung injury. We tested the null hypothesis that TH does not improve hyperoxic lung injury in neonatal rats. The prospective, randomized study was set at Research laboratory in Children's Hospital. Forty-five newborn rats were randomly assigned to three groups (n = 15/group), and exposed to 96 h of normoxia (FiO(2) = 0.21), hyperoxia (FiO(2) > 0.98), and TH (FiO(2) = 0.95, FiCO(2) = 0.05). Lung histology, wet-weight to dry-weight ratio, and concentrations of pro- and anti-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha, and IL-10) were used to evaluate pulmonary damage. Using a scale of 0-4, the total scores for lungs hypercellularity, inflammation, and hemorrhage was significantly increased from a median value of 1.5 in normoxia to 2.5 in hyperoxia (P < 0.05) and 3.0 with TH (P < 0.001, nonparametric ANOVA). The interstitial space relative to the alveolar space, as a measure of hypercellularity, was increased by 18% during hyperoxia and by 44% with TH compared with normoxia. TH significantly increased the size of the interstitial space by 22% compared with hyperoxia (P < 0.001). The lung wet-weight to dry-weight ratio was increased by 10% in both hyperoxic groups (P < 0.001). Both hyperoxic groups showed significant reductions in the concentration of IL-1beta compared with normoxia (P < 0.001), whereas the ratio of IL-1beta to IL-10 was significantly decreased, indicating an anti-inflammatory trend. TH does not prevent histological manifestations of hyperoxic lung injury in spontaneously breathing neonatal rats and may worsen the outcome.

A Case of Bilateral Spontaneous Chylothorax with Respiratory Syncytial Virus Bronchiolitis.

A case of bilateral spontaneous chylothorax with respiratory syncytial virus (RSV) bronchiolitis has never been reported. We report the case of a 7-month-old boy born at 33 weeks gestation with a history of Down syndrome, atrial septal defect, pulmonary hypertension, and chronic lung disease, hospitalized due to RSV bronchiolitis who developed bilateral spontaneous chylothorax with exacerbation of pulmonary hypertension (PH). The patient died after 9 weeks of mechanical ventilation and treatment for PH. The autopsy showed acute infectious signs, a chronic interstitial lung disease with pulmonary hypertensive changes and subpleural cysts with no evidence of congenital lymphangiectasia. The cause of chylothorax in this child could be multifactorial. However, worsening pulmonary hypertension with RSV infection might have partially contributed to the development of chylothorax through elevated superior venous cava pressure. Thoracentesis should be considered for patients with Down syndrome and PH associated with congenital heart disease who develop persistent pleural effusion during RSV bronchiolitis to rule out chylothorax.

Effect of patent ductus arteriosus on pulmonary vascular disease.

The hemodynamic effects of a patent ductus arteriosus (PDA) are well known including systemic hypoperfusion and volume overload on the left ventricle. This article aims to provide a review of the long-standing effect of a hemodynamically significant PDA on the pulmonary vasculature and the role of cardiac catheterization in preterm infants with a PDA and pulmonary hypertension.

The effects of CO2 on cytokine concentrations in endotoxin-stimulated human whole blood.

OBJECTIVES: Hypercapnia is known to modulate inflammation in lungs. However, the effect of hypocapnia and hypercapnia on blood cytokine production during sepsis is not well understood. We hypothesized that CO2 modulates ex vivo inflammatory cytokine production during endotoxin stimulation. To test this hypothesis, we measured the production of pro- and anti-inflammatory cytokines in endotoxin-stimulated human whole blood cultures under hypercapnic, normocapnic, and hypocapnic conditions. DESIGN: Prospective randomized study. SETTING: Basic research laboratory. SUBJECTS: Ten male and 10 female volunteers. INTERVENTIONS: Venous blood samples, taken from volunteers were cultured at 37 degrees C, under hypocapnic (2% CO2), normocapnic (5% CO2), and hypercapnic (7% CO2) conditions, with and without endotoxin stimulation. After 24 hrs of incubation, each culture's supernatant was analyzed for tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interleukin-10, and interferon-gamma concentrations by enzyme-linked immunosorbent assay. Data were analyzed using nonparametric repeated measures of analysis of variance followed by Dunn's multiple comparisons test. Analysis of variance with Bonferroni correction was used to compare gender differences in cytokine concentrations. The Pearson test was used to estimate correlation between hydrogen ion and individual cytokine concentrations. MEASUREMENTS AND MAIN RESULTS: Concentrations of the proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta and of the anti-inflammatory cytokine interleukin-10 under hypercapnic condition were significantly decreased (p < 0.05, 0.01, and 0.001, respectively) for both genders when compared with either normocapnic or hypocapnic conditions. Concentrations of tumor necrosis factor-alpha and interleukin-1beta were significantly higher in men. In women, concentrations of interleukin-6 were significantly decreased under hypercapnic condition when compared with hypocapnic condition. An inverse relationship was found between hydrogen ion concentration and concentrations of tumor necrosis factor-alpha and interleukin-10. CONCLUSIONS: Our results are consistent with the hypothesis that CO2 can affect the production of pro- and anti-inflammatory cytokines after ex vivo stimulation with endotoxin.

Transpyloric Feeding Tube Placement Using Electromagnetic Placement Device in Children.

BACKGROUND: Transpyloric feeding tubes (TPT) are often recommended in critically ill children. Blind tube placement, however, can be difficult, be time-consuming, and incur multiple radiation exposures. An electromagnetic device (EMD) is available for confirmation of successful placement of TPTs. We conducted a retrospective cohort study to evaluate the efficacy of an EMD for TPT placement in children and determine its impact on placement success, radiation exposure, confirmation time, and cost for tube placement compared with traditional blind TPT placement. MATERIALS AND METHODS: Retrospective data were collected in patients receiving a TPT before (pre-EMD group) and after implementation of an EMD (EMD group). RESULTS: Need for radiographic exposure decreased significantly in the EMD group (n = 40) compared with the pre-EMD group (n = 38) (0.6 vs 1.6 x-rays, P < .001). TPTs were placed and confirmed without abdominal x-ray in 21 of 40 patients in the EMD group. There were no serious adverse events such as misplacement into the lung or pneumothorax or perforation injury of the stomach. Successful tube confirmation took a significantly shorter time in the EMD group than in the pre-EMD group (1.45 vs 4.59 hours, P < .0001). There was an estimated cost savings of $245.10 per placement associated with decreased x-ray and fluoroscopy. CONCLUSION: The use of an EMD in children significantly decreased radiation exposure and confirmation time while maintaining TPT placement success. The use of an EMD can potentially offer large cost savings. Elimination of abdominal x-ray with EMD during TPT placement was achieved without any serious complications in approximately half of the children.

Severe Pulmonary Vascular Obstructive Disease After Neonatal Arterial Switch Operation for Simple Transposition of the Great Arteries.

Neonatal arterial switch operation for simple dextro-transposition of the great arteries (d-TGA) has almost eliminated the occurrence of pulmonary vascular obstructive disease compared to patients who underwent Mustard or Senning procedure at an older age. We report a case of a neonate with d-TGA and intact ventricular septum who underwent arterial switch operation and yet developed severe pulmonary vascular obstructive disease within two months.

Plasma Biomarker Analysis in Pediatric ARDS: Generating Future Framework from a Pilot Randomized Control Trial of Methylprednisolone: A Framework for Identifying Plasma Biomarkers Related to Clinical Outcomes in Pediatric ARDS.

OBJECTIVE: Lung injury activates multiple pro-inflammatory pathways, including neutrophils, epithelial, and endothelial injury, and coagulation factors leading to acute respiratory distress syndrome (ARDS). Low-dose methylprednisolone therapy (MPT) improved oxygenation and ventilation in early pediatric ARDS without altering duration of mechanical ventilation or mortality. We evaluated the effects of MPT on biomarkers of endothelial [Ang-2 and soluble intercellular adhesion molecule-1 (sICAM-1)] or epithelial [soluble receptor for activated glycation end products (sRAGE)] injury, neutrophil activation [matrix metalloproteinase-8 (MMP-8)], and coagulation (plasminogen activator inhibitor-1). DESIGN: Double-blind, placebo-controlled randomized trial. SETTING: Tertiary-care pediatric intensive care unit (ICU). PATIENTS: Mechanically ventilated children (0-18 years) with early ARDS. INTERVENTIONS: Blood samples were collected on days 0 (before MPT), 7, and 14 during low-dose MPT (n = 17) vs. placebo (n = 18) therapy. The MPT group received a 2-mg/kg loading dose followed by 1 mg/kg/day continuous infusions from days 1 to 7, tapered off over 7 days; placebo group received equivalent amounts of 0.9% saline. We analyzed plasma samples using a multiplex assay for five biomarkers of ARDS. Multiple regression models were constructed to predict associations between changes in biomarkers and the clinical outcomes reported earlier, including P/F ratio on days 8 and 9, plateau pressure on days 1 and 2, PaCO2 on days 2 and 3, racemic epinephrine following extubation, and supplemental oxygen at ICU discharge. RESULTS: No differences occurred in biomarker concentrations between the groups on day 0. On day 7, reduction in MMP-8 levels (p = 0.0016) occurred in the MPT group, whereas increases in sICAM-1 levels (p = 0.0005) occurred in the placebo group (no increases in sICAM-1 in the MPT group). sRAGE levels decreased in both MPT and placebo groups (p < 0.0001) from day 0 to day 7. On day 7, sRAGE levels were positively correlated with MPT group PaO2/FiO2 ratios on day 8 (r = 0.93, p = 0.024). O2 requirements at ICU transfer positively correlated with day 7 MMP-8 (r = 0.85, p = 0.016) and Ang-2 levels (r = 0.79, p = 0.036) in the placebo group and inversely correlated with day 7 sICAM-1 levels (r = -0.91, p = 0.005) in the MPT group. CONCLUSION: Biomarkers selected from endothelial, epithelial, or intravascular factors can be correlated with clinical endpoints in pediatric ARDS. For example, MPT could reduce neutrophil activation (⇓MMP-8), decrease endothelial injury (⇔sICAM-1), and allow epithelial recovery (⇓sRAGE). Large ARDS clinical trials should develop similar frameworks. TRIAL REGISTRATION: https://clinicaltrials.gov, NCT01274260.