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Patient: Male, 11 Final Diagnosis: Chromobacterium violaceum infection Symptoms: Abscess • fever • rash Medication: — Clinical Procedure: ECMO Specialty: Critical Care Medicine Objective: Rare disease Background: Chromobacterium violaceum (C. violaceum) is a facultative anaerobic gram-negative bacterium found in soil and water, especially in tropical and subtropical areas. Although infection in humans is rare, it is associated with significant morbidity. The bacterium is known for its resistance to multiple antimicrobials, and the possibility of relapse and reinfection. Presence of bacteremia, disseminated infection, and ineffective antimicrobial agents are predictors of mortality. Case Report: We report the case of a previously healthy 11-year-old male with C. violaceum sepsis who was exposed to stagnant water. He presented with severe septic shock and developed multi-organ system failure. Initial presumptive diagnosis was staphylococcal infection secondary to presence of skin abscesses resulting in antibiotic coverage with vancomycin, clindamycin, nafcillin and ceftriaxone. He also had multiple lung and liver abscesses. Once C. violaceum was identified, he received meropenem and ciprofloxacin, and was later discharged on ertapenem and trimethoprim-sulfamethoxazole (TMP-SMX) to complete a total of six months of antibiotics. He was diagnosed with chronic granulomatous disease (CGD) and is currently on prophylactic TMP-SMX and itraconazole. He has not had any relapses since his initial presentation. Conclusions: This case highlights the importance of considering C. violaceum as a relevant human pathogen, and considering it early in temperate regions, particularly in cases of fulminant sepsis associated with multi-organ abscesses. Once C. violaceum is identified, appropriate antimicrobial therapy should be started promptly, and sufficient duration of treatment is necessary for successful therapy.

Background Interferon-induced transmembrane protein 3 (IFITM3) restricts endocytic fusion of influenza virus. IFITM3 rs12252_C, a putative alternate splice site, has been associated with influenza severity in adults. IFITM3 has not been evaluated in pediatric influenza. Methods The Pediatric Influenza (PICFLU) study enrolled children with suspected influenza infection across 38 pediatric intensive care units during November 2008 to April 2016. IFITM3 was sequenced in patients and parents were genotyped for specific variants for family-based association testing. rs12252 was genotyped in 54 African-American pediatric outpatients with influenza (FLU09), included in the population-based comparisons with 1000 genomes. Splice site analysis of rs12252_C was performed using PICFLU and FLU09 patient RNA. Results In PICFLU, 358 children had influenza infection. We identified 22 rs12252_C homozygotes in 185 white non-Hispanic children. rs12252_C was not associated with influenza infection in population or family-based analyses. We did not identify the Δ21 IFITM3 isoform in RNAseq data. The rs12252 genotype was not associated with IFITM3 expression levels, nor with critical illness severity. No novel rare IFITM3 functional variants were identified. Conclusions rs12252 was not associated with susceptibility to influenza-related critical illness in children or with critical illness severity. Our data also do not support it being a splice site.

Background Hematopoietic cell transplant (HCT) may be a risk factor for morbidity and mortality from respiratory syncytial virus (RSV). Previous studies have been limited by small sample size. We took a multicenter approach with the goal of better understanding the epidemiology, risk factors, treatment, morbidity, and mortality associated with RSV infections among children with HCT in the United States. Methods A retrospective, multicenter, cohort study of pediatric HCT recipients were diagnosed with RSV infection between January 2010 and December 2014. Results Of the 1522 HCT, 47 (3%) patients were diagnosed with RSV. Of those with RSV, 9 (19.1%) were admitted to the pediatric intensive care unit (PICU), 6 (12.8%) received invasive mechanical ventilation, and 1 died. Prophylactic palivizumab was uncommon. All who required critical care received ribavirin vs 7.3% of those who did not (P = .004). Cobacterial infections were found in 16 patients and were not associated with the need for critical care. We examined potential risk factors for severity of RSV disease. In those who received invasive ventilation, 100% had one of the preidentified risk factors. Half of those requiring mechanical ventilation were diagnosed with RSV during their conditioning for transplant as opposed to only 2.4% of those that did not require invasive mechanical ventilation (P = .005). Conclusions In this multicenter cohort, RSV was not common in children following HCT. Few children infected with RSV required critical care and mortality was low. Those diagnosed with RSV during conditioning for transplant were at higher risk for invasive mechanical ventilation.

Pediatric Acute Lung Injury (ALI) is associated with a high mortality and morbidity, and dysregulation of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis and evolution of ALI. Here we examined MMP expression and activity in pediatric ALI compared with controls. MMP-8, -9, and to a lesser extent, MMP-2, -3, -11 and -12 were identified at higher levels in lung secretions of pediatric ALI patients compared with controls. Tissue Inhibitor of Matrix metalloproteinase-1 (TIMP-1), a natural inhibitor of MMPs was detected in most ALI samples, but MMP-9:TIMP-1 ratios were high relative to controls. In subjects who remained intubated for ≥10 days, MMP-9 activity decreased, with > 80% found in the latent form. In contrast, almost all MMP-8 detected at later disease course was constitutively active. Discriminating MMP-9:TIMP-1 ratios were found in those who had a prolonged ALI course. These results identify a specific repertoire of MMP isoforms in the lung secretions of pediatric ALI patients, and demonstrate inverse changes in MMPs -8 and -9 with protracted disease.

Objective To review the findings and to discuss the implications of hyperglycemia in critically ill children. Design A critical appraisal of an article with literature review. Findings In this single-center, retrospective cohort study, the authors report that the prevalence of hyperglycemia ranged from 16.7% to 75%, depending on the cutoff values (120 mg/dL, 150 mg/dL, and 200 mg/dL), among nondiabetic children admitted to a pediatric intensive care unit. Hyperglycemia correlated with an increased in-hospital mortality rate (relative risk, 2.5; 95% confidence interval, 1.26-4.93 for maximum glucose within 24 hrs, >150 mg/dL; and relative risk, 5.68; 95% confidence interval, 1.38-23.47 for highest glucose within 10 days, >120 mg/dL), as well as a longer length of stay in the pediatric intensive care unit. This finding is in concordance with other adult and pediatric studies. However, without adjustment for severity of illness, the study does not distinguish cause and effect, nor does it address the role of strict glucose control in this group of patients. Conclusions This study adds to the growing body of knowledge that associates the timing, intensity, duration, and variability of glycemia with outcomes in critically ill children. However, its limitations restrict drawing causal relationships and prevents insights regarding therapy.

Respiratory Syncytial Virus (RSV) is an important human pathogen associated with substantial morbidity and mortality. The present study tested the hypothesis that RSV infection would increase matrix metalloproteinase (MMP)-9 expression, and that MMP-9 inhibition would decrease RSV replication both in vitro and in vivo. RSV A2 infection of human bronchial epithelial cells increased MMP-9 mRNA and protein release. Cells transfected with siRNA against MMP-9 following RSV infection had lower viral titers. In RSV infected wild-type (WT) mice, MMP-9, airway resistance and viral load peaked at day 2 post infection, and remained elevated on days 4 and 7. RSV infected MMP-9 knockout (KO) mice had decreased lung inflammation. On days 2 and 4 post inoculation, the RSV burden was lower in the MMP-9 KO mice compared to WT controls. In conclusion, our studies demonstrate that RSV infection is a potent stimulus of MMP-9 expression both in vitro and in vivo. Reduction of MMP-9 (via siRNA knockdown, and in MMP-9 KO mice) resulted in decreased viral replication. Our findings suggest MMP-9 is a potential therapeutic target for RSV disease.

Autism spectrum disorder (ASD) has become one of the most common neurodevelopmental diagnoses, occurring in approximately 1 in 68 children in the United States (1). Physicians caring for children with autism during the child’s acute illness may face challenges in diagnosis and treatment that can negatively impact quality of care. The difficulties stem in large measure from the core features of the syndrome. Specifically, ASD is characterized by impairments in communication skills; impairments in reciprocal social interactions; and restricted, repetitive, and stereotyped patterns of behavior and interests (2, 3). In addition to these core diagnostic features, ASD is often accompanied by impairments in cognitive and adaptive functioning, attention deficit, sensory processing disorder, and aggression or self-injurious behavior (4). In the presence of an acute illness, it can be extremely difficult to disentangle the core behaviors of autism from other illnesses. This challenge is intensified in a subgroup of these children who have very little or no expressive language (often characterized as “non-verbal” or “minimally verbal”) (5).

Respiratory Syncytial Virus (RSV) is an important human pathogen associated with substantial morbidity and mortality. The present study tested the hypothesis that RSV infection would increase matrix metalloproteinase (MMP)-9 expression, and that MMP-9 inhibition would decrease RSV replication both in vitro and in vivo. RSV A2 infection of human bronchial epithelial cells increased MMP-9 mRNA and protein release. Cells transfected with siRNA against MMP-9 following RSV infection had lower viral titers. In RSV infected wild-type (WT) mice, MMP-9, airway resistance and viral load peaked at day 2 post infection, and remained elevated on days 4 and 7. RSV infected MMP-9 knockout (KO) mice had decreased lung inflammation. On days 2 and 4 post inoculation, the RSV burden was lower in the MMP-9 KO mice compared to WT controls. In conclusion, our studies demonstrate that RSV infection is a potent stimulus of MMP-9 expression both in vitro and in vivo. Reduction of MMP-9 (via siRNA knockdown, and in MMP-9 KO mice) resulted in decreased viral replication. Our findings suggest MMP-9 is a potential therapeutic target for RSV disease.

Introduction/Purpose Matrix metalloproteinases (MMP)-8 and -9 have been implicated in acute lung injury (ALI) in adults. Little is known about their role in pediatric ALI, particularly as the disease progresses from the acute, exudative phase to the chronic fibroproliferative phase. Methods Lower airway secretions from 26 pediatric patients (age Results Notable differences were seen in MMP-8 and MMP-9 expression profiles and regulation. Pooled samples from the first 10 days of ALI demonstrated up-regulation of MMP-8 (ALI 67 ± 24 ng/mg; 3.7-fold increase over control), and MMP-9 (ALI 599 ± 117 ng/mg; 2.6-fold increase over control), with MMP-9 activity exceeding MMP-8 (p Conclusion Our data suggest that in pediatric ALI, MMP-8 activity increases whereas MMP-9 activity decreases with disease progression. Determining whether this shifting MMP profile can be used as a marker for protracted respiratory failure or the development of the fibroproliferative stage in the pediatric population warrants further examination.

Purpose To highlight the need for pediatricians to have an awareness of metastatic thyroid carcinoma in the differential diagnosis of pulmonary miliary lesions by presenting an unusual case presentation. Method We report a previously healthy 4-year-old female patient with a 9-week history of persistent cough and exertional dyspnea associated with decreased appetite and weight lost. The review of systems was positive for exposure to Mycobacterium tuberculosis in her first year of life from her biological mother but otherwise negative. Her physical exam was notable for bilateral cervical lymphadenopathy, with the largest node measuring approximately 5 3 4 cm. Thyroid exam was normal. Chest roentgenogram revealed diffuse nodular densities in both lung fields. An extensive diagnostic work-up was undertaken to identify Mycobacterium tuberculosis as the causative agent. A skin PPD test was nonreactive and gastric lavages failed to identify acid fast bacilli with Ziehl-Neelsen stain and direct fluorescent antibody. Silver stain for fungal elements and HIV titers were also negative. A subsequent lung bronchoscopy revealed compression of the left lung bronchus and microscopic analysis of the bronchoalveolar lavage fluid demonstrated normal cellular distribution with no microbial pathogens. A fine-needle biopsy of her cervical lymph node revealed metastatic thyroid carcinoma. The metastatic nature of the miliary pulmonary lesions was confirmed by avid uptake of radioactive iodine by the lesions. Results Thyroid carcinoma is uncommon in the pediatric population, with an annual incidence of 0.02-0.3 cases per 100,000 population. It typically manifests as an asymptomatic mass in 60-80% of cases and often presents with advanced disease in children. Extensive regional nodal involvement has been reported in up to 70% of pediatric patients with distant metastasis to the lungs, bone, or liver present in 10-20% of patients. Diffuse miliary spread to the lungs is unusual, with bilateral total lung involvement reported only in several cases. Conclusion During the evaluation and diagnosis of diffuse interstitial lung lesions in pediatrics, it is important to identify any suspected infectious pathogens. When an infectious etiology is not identified, examination of tissues by nodal and/or lung biopsy is often necessary to confirm the diagnosis. Miliary dissemination of thyroid carcinoma is an unusual cause of diffuse interstitial nodular pulmonary infiltrates.