Pulmonary surveillance in pediatric hematopoietic stem cell transplant: A multinational multidisciplinary survey.

BACKGROUND: Hematopoietic Stem Cell Transplant (HSCT) is an established treatment for malignant and non-malignant conditions and pulmonary disease is a leading cause of late term morbidity and mortality. Accurate and early detection of pulmonary complications is a critical step in improving long term outcomes. Existing guidelines for surveillance of pulmonary complications post-HSCT contain conflicting recommendations. AIM: To determine the breadth of current practice in monitoring for pulmonary complications of pediatric HSCT. METHODS: An institutional review board approved, online, anonymous multiple-choice survey was distributed to HSCT and pulmonary physicians from the United States of America and Australasia using the REDcap platform. The survey was developed by members of the American Thoracic Society Working Group on Complications of Childhood Cancer, and was designed to assess patient management and service design. RESULTS: A total of 40 (34.8%) responses were received. The majority (62.5%) were pulmonologists, and 82.5% were from the United States of America. In all, 67.5% reported having a protocol for monitoring pulmonary complications and 50.0% reported adhering "well" or "very well" to protocols. Pulmonary function tests (PFTs) most commonly involved spirometry and diffusion capacity for carbon monoxide. The frequency of PFTs varied depending on time post-HSCT and presence of complications. In all, 55.0% reported a set threshold for a clinically significant change in PFT. CONCLUSIONS: These results illustrate current variation in surveillance for pulmonary complications of pediatric HSCT. The results of this survey will inform development of future guidelines for monitoring of pulmonary complications after pediatric HSCT.

American Thoracic Society 2019 Pediatric Core Curriculum.

The American Thoracic Society Pediatric Core Curriculum updates clinicians annually in pediatric pulmonary disease in a 3 to 4 year recurring cycle of topics. The 2019 course was presented in May during the Annual International Conference. An American Board of Pediatrics Maintenance of Certification module and a continuing medical education exercise covering the contents of the Core Curriculum can be accessed online at www.thoracic.org.

Biology and management of methicillin resistant Staphylococcus aureus in cystic fibrosis.

Staphylococcus aureus is one of the earliest bacteria isolated from the respiratory tract in people with cystic fibrosis (CF). Its methicillin resistant form, MRSA, has gained attention due to the rapid increase in the last decades and worse outcomes with chronic infection. In the United States, prevalence of MRSA in CF is around 27%, but is much lower (3-18%) in most other countries. Methicillin is typically genetically encoded by the mecA gene, which encodes for an alternative penicillin binding protein (PRBa). This PRBa has low affinity to ß-lactams, thereby enabling growth of S. aureus in the presence of penicillinase resistant penicillins and most other ß-lactams. Non-mecA positive strains of MRSA, so-called borderline resistant (BORSA) have also been described. In addition to production of toxins, the virulence of S. aureus is conferred by its adaptability allowing persistence in face of antibiotic therapies and host defense. These adaptive growth mechanisms include small colony variants, biofilms, and growth under anaerobic conditions. Several reports have described successful eradication of MRSA, yet only two randomized trials of eradication during early infection have been conducted. A list of MRSA specific antibiotics with dosing relevant to CF patients is presented here. Many of these require special dosing in people with CF. Novel antibiotics are in trials for skin and soft tissue infections and it is unclear if and when those might be available for lung infections. Thus the best strategies for MRSA would be primary prevention.

Surfactant deficiency syndrome in an infant with a C-terminal frame shift in ABCA3: A case report.

Deficiency in ATP binding cassette A3 (ABCA3) causes neonatal respiratory distress, hypoxemic respiratory failure, and interstitial lung disease. ABCA3 transports phospholipids into the lamellar bodies of type II alveolar cells, a critical step in alveolar surfactant production. We report a term infant with ABCA3 surfactant deficiency syndrome with the E292V (c.875A>T; p.Glu292Val) mutation in trans with a novel C-terminal frame shift mutation (c.4938delC; p.Met1647fs). This mutation removes the final 58 amino acids and substitutes 33 incorrect amino acids. The frame shift spares membrane spanning and nucleotide binding domains, but disrupts a highly conserved C-terminal domain, which includes sequence motifs necessary for the function of human paralogs ABCA1, ABCA4, and the bacterial homolog DrrA. This observation suggests the C-terminal domain is also required for normal function of ABCA3.

Ranolazine overdose-induced seizures.

Ranolazine is a new anti-anginal medication that was approved by the US Food and Drug Administration (FDA) in 2006 for patients with symptomatic chronic angina despite optimized therapy. This paper presents a case report of a fifteen year old male patient admitted to the pediatric intensive care unit after ranolazine overdose ingestion. He had recurrent new onset seizures that are most likely due to ranolazine overdose. Seizures have never been reported with ranolazine use or abuse.