Clinical course of sly syndrome (mucopolysaccharidosis type VII).

BACKGROUND: Mucopolysaccharidosis VII (MPS VII) is an ultra-rare disease characterised by the deficiency of ß-glucuronidase (GUS). Patients' phenotypes vary from severe forms with hydrops fetalis, skeletal dysplasia and mental retardation to milder forms with fewer manifestations and mild skeletal abnormalities. Accurate assessments on the frequency and clinical characteristics of the disease have been scarce. The aim of this study was to collect such data. METHODS: We have conducted a survey of physicians to document the medical history of patients with MPS VII. The survey included anonymous information on patient demographics, family history, mode of diagnosis, age of onset, signs and symptoms, severity, management, clinical features and natural progression of the disease. RESULTS: We collected information on 56 patients from 11 countries. Patients with MPS VII were classified based on their phenotype into three different groups: (1) neonatal non-immune hydrops fetalis (NIHF) (n=10), (2) Infantile or adolescent form with history of hydrops fetalis (n=13) and (3) Infantile or adolescent form without known hydrops fetalis (n=33). Thirteen patients with MPS VII who had the infantile form with history of hydrops fetalis and survived childhood, had a wide range of clinical manifestations from mild to severe. Five patients underwent bone marrow transplantation and one patient underwent enzyme replacement therapy with recombinant human GUS. CONCLUSIONS: MPS VII is a pan-ethnic inherited lysosomal storage disease with considerable phenotypical heterogeneity. Most patients have short stature, skeletal dysplasia, hepatosplenomegaly, hernias, cardiac involvement, pulmonary insufficiency and cognitive impairment. In these respects it resembles MPS I and MPS II. In MPS VII, however, one unique and distinguishing clinical feature is the unexpectedly high proportion of patients (41%) that had a history of NIHF. Presence of NIHF does not, by itself, predict the eventual severity of the clinical course, if the patient survives infancy.

Balancing the Tension Between Hyperoxia Prevention and Alarm Fatigue in the NICU.

BACKGROUND: After the implementation of narrowed oxygen saturation alarms, alarm frequency increased in the C.S. Mott Children's Hospital NICU which could have a negative impact on patient safety. The Joint Commission on the Accreditation of Healthcare Organizations issued a Sentinel Event Alert for hospitals in 2013 to improve alarm safety, resulting in a 2014 National Patient Safety Goal requiring institutional policies and procedures to be in place to manage alarms. METHODS: A multidisciplinary improvement team developed an alarm management bundle applying strategies to decrease alarm frequency, which included evaluating existing strategies and developing patient care-based and systems-based interventions. The total number of delivered and detected saturation alarms and high saturation alarms and the total time spent within a targeted saturation range were quantitatively tracked. Nursing morale was assessed qualitatively. RESULTS: SpO2 alarms per monitored patient-day increased from 78 to 105 after the narrowing of alarm limits. Modification of the high saturation alarm algorithm substantially decreased the delivery and escalation of high pulse oxygen saturation (SpO2) alarms. During a pilot period, using histogram technology to individually customize alarm limits resulted in increased time spent within the targeted saturation range and fewer alarms per day. Qualitatively, nurses reported improved satisfaction when not assigned >1 infant with frequent alarms, as identified by an alarm frequency tool. CONCLUSIONS: Alarm fatigue may detrimentally affect patient care and safety. Alarm management strategies should coincide with oxygen management within a NICU, especially in single-patient-bed units.

Surfactant-associated proteins: structure, function and clinical implications.

Surfactant replacement therapy is now the standard of care for infants with respiratory distress syndrome. As the understanding of surfactant structure and function has evolved, surfactant-associated proteins are now understood to be essential components of pulmonary surfactant. Their structural and functional diversity detail the complexity of their contributions to normal pulmonary physiology, and deficiency states result in significant pathology. Engineering synthetic surfactant protein constructs has been a major research focus for replacement therapies. This review highlights what is known about surfactant proteins and how this knowledge is pivotal for future advancements in treating respiratory distress syndrome as well as other pulmonary diseases characterized by surfactant deficiency or inactivation.

Surfactant protein A binds flagellin enhancing phagocytosis and IL-1ß production.

Surfactant protein A (SP-A), a pulmonary collectin, plays a role in lung innate immune host defense. In this study the role of SP-A in regulating the inflammatory response to the flagella of Pseudomonas aeruginosa (PA) was examined. Intra-tracheal infection of SP-A deficient (SP-A-/-) C57BL/6 mice with wild type flagellated PA (PAK) resulted in an increase in inflammatory cell recruitment and increase in pro-inflammatory cytokines IL-6 and TNF-α, which was not observed with a mutant pseudomonas lacking flagella (fliC). SP-A directly bound flagellin, via the N-linked carbohydrate moieties and collagen-like domain, in a concentration dependent manner and enhanced macrophage phagocytosis of flagellin and wild type PAK. IL-1ß was reduced in the lungs of SP-A-/- mice following PAK infection. MH-s cells, a macrophage cell line, generated greater IL-1ß when stimulated with flagellin and SP-A. Historically flagella stimulate IL-1ß production through the toll-like receptor 5 (TLR-5) pathway and through a caspase-1 activating inflammasome pathway. IL-1ß expression became non-detectable in SP-A and flagellin stimulated MH-s cells in which caspase-1 was silenced, suggesting SP-A induction of IL-1ß appears to be occurring through the inflammasome pathway. SP-A plays an important role in the pathogenesis of PA infection in the lung by binding flagellin, enhancing its phagocytosis and modifying the macrophage inflammatory response.