Whyte, Michael P.; McAlister, William H.; and et al, ,"Enzyme-replacement therapy in life-threatening hypophosphatasia." The New England Journal of Medicine.366,10. 904-913. (2012).

Hutchinson–Gilford progeria syndrome (HGPS) is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA that produces the farnesylated aberrant lamin A protein, progerin. This multisystem disorder causes failure to thrive and accelerated atherosclerosis leading to early death. Farnesyltransferase inhibitors have ameliorated disease phenotypes in preclinical studies. Twenty-five patients with HGPS received the farnesyltransferase inhibitor lonafarnib for a minimum of 2 y. Primary outcome success was predefined as a 50% increase over pretherapy in estimated annual rate of weight gain, or change from pretherapy weight loss to statistically significant on-study weight gain. Nine patients experienced a ≥50% increase, six experienced a ≥50% decrease, and 10 remained stable with respect to rate of weight gain. Secondary outcomes included decreases in arterial pulse wave velocity and carotid artery echodensity and increases in skeletal rigidity and sensorineural hearing within patient subgroups. All patients improved in one or more of these outcomes. Results from this clinical treatment trial for children with HGPS provide preliminary evidence that lonafarnib may improve vascular stiffness, bone structure, and audiological status.

Congenital lung anomalies vary widely in their clinical manifestation and imaging appearance. Although radiographs play a role in the incidental detection and initial imaging evaluation in patients with clinical suspicion of congenital lung anomalies, cross-sectional imaging such as computer tomography (CT) is frequently required for confirmation of diagnosis, further characterization, and preoperative evaluation in the case of surgical lesions. Recently, with the development and widespread availability of multidetector CT scanners, CT has assumed a greater role in the noninvasive evaluation of congenital lung anomalies. The combination of fast speed, high spatial resolution, and enhanced quality of multiplanar reformation and three-dimensional reconstructions makes multidetector CT an ideal noninvasive method for evaluating congenital lung anomalies. In this article, the authors review the multidetector CT technique for evaluation of congenital lung anomalies. Important clinical aspects, characteristic imaging features, and key points that allow differentiation among various anomalies are highlighted for a variety of common and uncommon conditions.

Necrotising pneumonia (NP) is a severe complication of community-acquired pneumonia characterised by liquefaction and cavitation of lung tissue. The present study describes the epidemiology, aetiology, management and outcomes of children hospitalised with NP over a 15-yr period. A retrospective observational study of NP cases was conducted from January 1990 to February 2005 analysing clinical presentation, laboratory data, hospital course and long-term follow-up. A total of 80 NP cases were identified, with the number of detected cases increasing from 12, in the period 1993-1996, to 40 in the period 2001-2004. In total, 69 (86%) cases had pleural effusion with a low pH (mean 7.08) and 38 (48%) patients had positive cultures, with Streptococcus pneumoniae as the predominant organism. Recently, other organisms, most notably methicillin-resistant Staphylococcus aureus, emerged. Patients had prolonged hospitalisations (median 12 days). A total of 69 patients required pleural interventions and those receiving chest drainage alone had similar outcomes to those managed surgically. All patients had full clinical resolution within 2 months of presentation. Necrotising pneumonia has increasingly been identified as a complication of paediatric pneumonia. Streptococcus pneumoniae remains the predominant organism, but since 2002, different bacteria have been isolated and the age range of cases has broadened. Despite the serious morbidity, massive parenchymal damage and prolonged hospitalisations, long-term outcome following necrotising pneumonia is excellent.