Developmental Regulation of Effector and Resident Memory T Cell Generation during Pediatric Viral Respiratory Tract Infection.

Viral respiratory tract infections (VRTI) remain a leading cause of morbidity and mortality among infants and young children. In mice, optimal protection to VRTI is mediated by recruitment of effector T cells to the lungs and respiratory tract, and subsequent establishment of tissue resident memory T cells (Trm), which provide long-term protection. These critical processes of T cell recruitment to the respiratory tract, their role in disease pathogenesis, and establishment of local protective immunity remain undefined in pediatric VRTI. In this study, we investigated T cell responses in the upper respiratory tract (URT) and lower respiratory tract (LRT) of infants and young children with VRTI, revealing developmental regulation of T cell differentiation and Trm generation in situ. We show a direct concurrence between T cell responses in the URT and LRT, including a preponderance of effector CD8+ T cells that was associated with disease severity. During infant VRTI, there was an accumulation of terminally differentiated effector cells (effector memory RA+ T cells) in the URT and LRT with reduced Trm in the early neonatal period, and decreased effector memory RA+ T cell and increased Trm formation with age during the early years of childhood. Moreover, human infant T cells exhibit increased expression of the transcription factor T-bet compared with adult T cells, suggesting a mechanism for preferential generation of effector over Trm. The developmental regulation of respiratory T cell responses as revealed in the present study is important for diagnosing, monitoring, and treating VRTI in the critical early life stages.

Heart Failure and Hypothermia in an Infant: Pseudocyanide Syndrome?

PURPOSE: Mixed or central venous oxygen saturation has not been described during concurrent heart failure and hypothermia in children, both of which may be associated with hyperlactatemia. This report of an infant with heart failure and hypothermia is significant for increased inferior vena cava (IVC) oxygen saturation and hyperlactatemia. CASE REPORT: A 36-day-old female was fussy for a day and then developed respiratory distress. In the Pediatric ER, she was tachycardic (260 beats/minute) and hypothermic (32.4 degrees C) with prolonged capillary refill and faint distal pulses. Adenosine was given twice via an intraosseous line for supraventricular tachycardia, with conversion to sinus rhythm. Blood drawn from an IVC catheter was significant for uncorrected (for temperature) oxygen saturation of 94% and lactate 18 mmol/L; corrected and uncorrected IVC oxygen saturation early during rewarming were >90%. During rewarming, declines in uncorrected IVC oxygen saturation and lactate correlated. Hypothermia and hyperlactatemia resolved after 10 and 12 hours. CONCLUSIONS: Concurrent heart failure and hypothermia in an infant were associated with increased IVC oxygen saturation and hyperlactatemia, similar to lab findings associated with a mitochondrial toxin such as cyanide. Improvement of heart failure and hypothermia were associated with resolution of these lab abnormalities, thus helping to rule out mitochondrial toxins. Additional reports may help better define a pseudocyanide syndrome in this setting.

Sieving and extraction of peptides and proteins during hemofiltration: a systematic review
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The relationship between the sieving coefficient (SC) or extraction ratio (ER) and the molecular weight (MW) of peptide and protein solutes during hemofiltration has not been investigated; it is possible that the SC and ER correlate with MW, permitting an estimate of peptide and protein clearance by hemofiltration in the absence of empiric data. A search for studies of the SC and/or ER for peptide and protein solutes during hemofiltration identified data for ß2-microglobulin, brain natriuretic peptide, carperitide, IL-1ß, IL-1RA, IL-6, IL-8, lysozyme, myoglobin, neutrophil gelatinase-associated lipocalin, procalcitonin, retinol-binding protein, TNF-α, soluble TNFR-1, soluble TNFR-II, and vasopressin using polyacrylonitrile, polysulfone, polyamide, and cellulose hemofilters. The SC correlated with MW using polyacrylonitrile, polyamide, and cellulose hemofilters. With fewer data, the ER did not correlate with MW using polyacrylonitrile hemofilters, and not enough data were available to assess the ER with any other hemofilters. These results may help predict peptide and protein convective clearance during hemofiltration with polyacrylonitrile, polyamide, and cellulose hemofilters when empiric data are not available.
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Vitamin B deficiencies in a critically ill autistic child with a restricted diet.

An 11-year-old male with autism became less responsive and was hospitalized with hepatomegaly and liver dysfunction, as well as severe lactic acidosis. His diet for several years was self-limited exclusively to a single "fast food"-a particular type of fried chicken-and was deficient in multiple micronutrients, including the B vitamins thiamine and pyridoxine. Lactic acidosis improved rapidly with thiamine; 2 weeks later, status epilepticus-with low serum pyridoxine-resolved rapidly with pyridoxine. Dietary B vitamin deficiencies complicated the care of this critically ill autistic child and should be considered in this setting.

Severe hemorrhagic coagulopathy with hemophagocytic lymphohistiocytosis secondary to Epstein-Barr virus-associated T-cell lymphoproliferative disorder.

OBJECTIVE: We describe the coagulopathy and hemorrhagic complications associated with fulminant, secondary hemophagocytic lymphohistiocytosis in a cohort of patients with Epstein-Barr virus-associated T-cell lymphoproliferative disorder. PATIENTS AND METHODS: Institutional Review Board-approved retrospective review of all patients at our children's hospital over 3 years (2008-2010) with hemophagocytic lymphohistiocytosis secondary to acute Epstein-Barr virus-associated T-cell lymphoproliferative disorder. RESULTS: Four males (2, 3, 17, and 20 yr old) presented with fever, hepatosplenomegaly, and pancytopenia with elevated serum ferritin, and all met clinical and laboratory criteria for secondary hemophagocytic lymphohistiocytosis. d-dimer on admission was elevated in all patients and remained extremely elevated during hospitalization, while the median prothrombin and activated partial thromboplastin times as well as fibrinogen were all in the normal range. Within a few weeks to months following admission, all patients developed multiorgan system failure with episodes of severe, life-threatening hemorrhage; in all four patients, hemorrhage was not associated with a nadir in platelet count. There were no survivors beyond 4 months from diagnosis. CONCLUSIONS: A coagulopathy characterized by persistent, extreme elevations in plasma d-dimer and severe, life-threatening hemorrhage was noted in association with hemophagocytic lymphohistiocytosis secondary to Epstein-Barr virus-associated T-cell lymphoproliferative disorder. We speculate that this coagulopathy is a marker of severe hemophagocytic lymphohistiocytosis in this setting.

Nitric oxide-associated pulmonary edema in children with pulmonary venous hypertension.

Nitric oxide (NO)-associated pulmonary edema is rarely reported in children; in adults, it is often associated with left-sided heart failure. We report a case series of children with NO-associated pulmonary edema, which was defined as new multilobar alveolar infiltrates and worsening hypoxemia within 24 h of initiation or escalation of NO and radiologic or clinical improvement after NO discontinuation. We identified six patients (0.4-4 years old) with ten episodes of NO-associated pulmonary edema. Diagnoses included atrioventricular canal defect with mitral valve disease (n = 2), pulmonary atresia and major aorta-pulmonary collateral arteries (n = 2), total anomalous pulmonary venous return (n = 1), and pulmonary veno-occlusive disease (n = 1). All patients had evidence of pulmonary venous hypertension, and two had mitral valve disease resulting in clinical evidence of left-sided heart failure. Pulmonary edema improved or resolved within 24 h of discontinuing NO. At cardiac catheterization, mean left atrial pressure was <15 mmHg in three of three patients (none with mitral valve disease), whereas pulmonary artery occlusion pressure was >15 mmHg in two of five patients. In conclusion, we describe six young children with NO-associated pulmonary edema and pulmonary venous hypertension. Only two of these children had left-sided heart failure: Left atrial pressure as well as pulmonary artery occlusion pressure may not be helpful in identifying children at risk for NO-associated pulmonary edema.

Comparing the clinical severity of the first versus second wave of 2009 Influenza A (H1N1) in a New York City pediatric healthcare facility.

OBJECTIVE: We previously reported the epidemiology of 2009 Influenza A (H1N1) in our pediatric healthcare facility in New York City during the first wave of illness (May-July 2009). We hypothesized that compared with the first wave, the second wave would be characterized by increased severity of illness and mortality. DESIGN: : Case series conducted from May 2009 to April 2010. SETTING: Pediatric emergency departments and inpatient facilities of New York-Presbyterian Hospital. PATIENTS: All hospitalized patients ÷ 18 yrs of age with positive laboratory tests for influenza A. MEASUREMENTS AND MAIN RESULTS: We compared severity of illness during the first and second wave assessed by the number of hospitalized children, including those in the pediatric intensive care unit, bacterial superinfections, and mortality rate. Compared to the first wave, fewer children were hospitalized during the second wave (n = 115 vs. 76), but a comparable portion were admitted to the pediatric intensive care unit (30.4% vs. 19.7%; p = .10). Pediatric Risk of Mortality III scores, length of hospitalization in the pediatric intensive care unit, incidence of respiratory failure and pneumonia, and peak oxygenation indices were similar during both waves. Bacterial superinfections were comparable in the first vs. second wave (3.5% vs. 1.3%). During the first wave, no child received extracorporeal membrane oxygenation and one died, while during the second wave, one child received extracorporeal membrane oxygenation and there were no deaths. CONCLUSIONS: At our pediatric healthcare facility in New York City, fewer children were hospitalized with 2009 Influenza A (H1N1) during the second wave, but both waves had a similar spectrum of illness severity and low mortality rate.

Long-duration (>4 weeks) continuous renal replacement therapy in critical illness.

INTRODUCTION: Decreased pediatric survival has been reported with long-duration (>4 weeks) continuous renal replacement therapy (CRRT), though the practice has not been well-described. METHODS: Retrospective chart review in a children's hospital of all patients treated with CRRT over 2 years (2003-4), including those who underwent long (group 1) and shorter duration (group 2) therapy. RESULTS: We identified 39 patients: median age was 6 years (range: 0.3-23; 7 were infants), median PRISM III score was 16 (range: 4-35), and the most frequent primary diagnosis was a stem cell transplant (in 12 out of 39). At continuous renal replacement therapy initiation, almost all patients (38 out of 39) had multiorgan dysfunction syndrome, most (35 out of 39) were being treated with at least one inotrope or vasopressor, and median fluid overload was 18% (range: 1-43%). Survival was poor (38%). Groups 1 (n = 7) and 2 (n = 32) had similar age (p = 0.44), PRISM III score (p = 0.61), and stem cell transplant diagnosis (p = 0.65). At CRRT initiation, the incidence of multiorgan dysfunction syndrome (p=0.18), inotrope or vasopressor treatment (p = 0.56), and fluid overload severity (p = 0.71) were similar. Those in group 1 had a longer mean CRRT as well as persistent cardiovascular dysfunction limiting the utility of intermittent dialysis. Survival was similar between groups (p = 1). CONCLUSIONS: Critically-ill patients treated with long and shorter duration CRRT had a similar survival rate.

The sieving coefficient and clearance of vasopressin during continuous renal replacement therapy in critically ill children.

HYPOTHESIS: As vasopressin is a small peptide, its sieving coefficient (SC) and clearance (CL) during continuous renal replacement therapy may be intermediate to those for urea and ß2 microglobulin (commonly used markers for small- and middle-molecular weight solutes, respectively). METHODS: A prospective, minimal-risk study was undertaken of the SC and CL of vasopressin in critically ill children on the first day of continuous renal replacement therapy using AN69 membrane filters and prefilter replacement fluid. All prefilter plasma (vasopressin) samples were drawn from the arterial port after predilution. RESULTS: Nine patients with fluid overload, renal failure, or both were recruited (median age, 14 years) during the first day of either continuous venovenous hemofiltration (n = 3) or hemodiafiltration (n = 6). Multiorgan dysfunction syndrome was present in 8 patients, and 3 were in shock (2 were receiving a vasopressin infusion). Median prefilter plasma (vasopressin) was 1.7 pg/mL, although data points were skewed: 5 patients had a low prefilter plasma (vasopressin) (<2 pg/mL), and 4 patients (including 2 receiving a continuous vasopressin infusion) had a prefilter plasma (vasopressin) between 4.2 and 56.4 pg/mL. All those with low prefilter plasma (vasopressin) had an effluent (vasopressin) less than the detection limit (0.6 pg/mL). The median SC was 1 in the 4 patients with a measurable effluent (vasopressin), and their median filter CL was 48 mL/min or 39 mL/(min 1.73 m(2)). CONCLUSIONS: The SC and CL of vasopressin by continuous venovenous hemofiltration or hemodiafiltration in these critically ill children were similar to values for urea.

Novel influenza A(H1N1) in a pediatric health care facility in New York City during the first wave of the 2009 pandemic.

OBJECTIVE: To describe the burden of care experienced by our pediatric health care facility in New York, New York, from May 3, 2009, to July 31, 2009, during the novel influenza A(H1N1) pandemic that began in spring 2009. DESIGN: Retrospective case series. SETTING: Pediatric emergency departments and inpatient facilities of New York-Presbyterian Hospital. Patients Children presenting to the emergency departments with influenza-like illness (ILI) and children aged 18 years or younger hospitalized with positive laboratory test results for influenza A from May 3, 2009, to July 31, 2009. MAIN OUTCOME MEASURES: Proportion of children with ILI who were hospitalized and proportion of hospitalized children with influenza A with respiratory failure, bacterial superinfection, and mortality. RESULTS: When compared with the same period in 2008, the pediatric emergency departments experienced an excess of 3750 visits (19.9% increase). Overall, 27.7% of visits were for ILI; 2.5% of patients with ILI were hospitalized. Of the 115 hospitalized subjects with confirmed influenza A (median age, 4.3 years), 93 (80.9%) had underlying conditions. Four (3.5%) had identified bacterial superinfection, 1 (0.9%) died, and 35 (30.4%) were admitted to a pediatric intensive care unit; of these 35 patients, 11 had pneumonia and required mechanical ventilation, including high-frequency oscillatory ventilation (n = 3). CONCLUSIONS: At our center, 2.5% of children with ILI presenting to the emergency departments during the first wave of the 2009 novel influenza A(H1N1) pandemic were hospitalized. Of the 115 hospitalized children with confirmed influenza A, 9.6% had respiratory failure and 0.9% died. These findings can be compared with the disease severity of subsequent waves of the 2009 novel influenza A(H1N1) pandemic.

Massive pulmonary embolism in children.

We present 3 children with massive pulmonary embolism and review 17 recent pediatric reports. Malignancies were a frequent cause (40%), and sudden death was common (60%). Compared with adults, diagnosis was more likely to be made at autopsy (P < .0001), more children were treated with embolectomy/thrombectomy (P = .0006), and mortality was greater (P = .03).

Noninvasive ventilation during pediatric interhospital ground transport.

OBJECTIVE: We report our use of noninvasive ventilation (NIV) during pediatric interhospital ground transport. METHODS: We retrospectively reviewed transport and hospital records for nonneonatal patients

Massive pulmonary embolus without hypoxemia.

OBJECTIVE: To describe a patient who had been taking ibuprofen for 3 days before the diagnosis of a massive pulmonary embolus without hypoxemia. DESIGN: Institutional review board-approved case report. SETTING: Pediatric intensive care unit. PATIENT: A 16-yr-old male with a history of supraventricular tachycardia. RESULTS: The patient underwent an electrophysiology study and developed mild shortness of breath and then chest pain 2 and 4 days later, respectively. He took ibuprofen for 3 days. Evaluation 1 wk following the procedure revealed dyspnea and tachycardia. Arterial blood gas in room air was significant for hypocarbia without hypoxemia (Pao2, 108 mm Hg; Paco2, 28 mm Hg). Ventilation perfusion scan and computed axial tomography with intravenous contrast were consistent with a massive pulmonary embolus and left external iliac vein thrombus. He received anticoagulation, thrombolysis, a stent in the left iliac vein, and a filter in the inferior vena cava. Perfusion gradually improved and he was discharged home on oral anticoagulation. CONCLUSIONS: The absence of hypoxemia (including a normal alveolar-arterial oxygen difference) in our patient with a massive pulmonary embolus may have been related to cyclooxygenase inhibition due to ibuprofen, with improvement in ventilation-perfusion mismatch.

Spinal muscular atrophy type 1: management and outcomes.

Our objectives were to describe survival, hospitalization, speech, and outcomes related to respirator needs for spinal muscular atrophy type 1 (SMA1) patients, using noninvasive or tracheostomy ventilation. From 65 SMA patients referred to our clinic since 1996, we chose 56 SMA1 patients who developed respiratory failure before age 2 years. Patients either had tracheostomy tubes (group A), or used noninvasive ventilation and assisted coughing; a previously reported extubation protocol (group B) was used as needed. Sixteen patients underwent tracheostomy at 10.8 +/- 5.0 months of age, 33 were in group B, and 7 others died without life-support interventions. Compared to group B, group A patients had fewer hospitalizations until age 3 years, but more after age 5, and 15 of 16 lost all spontaneous breathing tolerance posttracheostomy and could not speak. One group A patient died at 16 months of age, and the others were 73.8 +/- 57 months of age (the oldest was 19 years old). Two group B patients died at 6 and 13 months, respectively, whereas the other 31 were 41.8 +/- 26.0 months (and up to 8.3 years) old. Three of 31 in group B required high-span positive inspiratory pressure plus positive end-expiratory pressure (PIP + PEEP) continuously with minimal tolerance for breathing on their own, and 4 could not communicate verbally.In conclusion, SMA type 1 children can survive beyond 2 years of age when offered tracheostomy or noninvasive respiratory support. The latter is associated with fewer hospitalizations after age 5 years, freedom from daytime ventilator use, and the ability to speak.