Bacteriophage Therapy for Pan-Drug-Resistant Pseudomonas aeruginosa in Two Persons With Cystic Fibrosis.

Cystic fibrosis (CF) is an important monogenic disease that affects more than 70 000 people worldwide. Defects of the CF transmembrane conductance regulator gene lead to dehydrated viscous secretions that result in chronic bacterial colonization. This leads to frequent recurrent lung infections called pulmonary exacerbations, lung inflammation, and resulting structural lung damage called bronchiectasis. Pseudomonas aeruginosa in particular is a common pathogen in persons with CF associated with increased pulmonary exacerbations, long-term lung function decline, and reduced survival. In addition, P. aeruginosa commonly develops antibiotic resistance and forms biofilms, making it difficult to treat. Here, we report the details of two patients with CF with pan-drug-resistant P. aeruginosa who were treated with a novel therapeutic strategy, bacteriophages. These cases highlight the need for further research and development of this treatment modality, including pediatric clinical trials.

Physical Activity in Youth with Down Syndrome and Its Relationship with Adiposity.

PURPOSE: The aims of this study are to (1) compare physical activity (PA) and sedentary activity (SA) in youth with and without Down syndrome (DS and non-DS) and examine the relationships of PA and SA with their traditional risk factors (age, sex, race, and body mass index Z score [BMI-Z]) and (2) explore the relationship of PA with visceral fat (VFAT) in both groups. METHODS: SenseWear accelerometry data from at least 2 weekdays and 1 weekend day were collected from youth with DS (N = 77) and non-DS (N = 57) youth. VFAT was measured by dual x-ray absorptiometry. RESULTS: In age-, sex-, race-, and BMI-Z-adjusted models, those with DS engaged in more minutes of light PA (LPA) ( p < 0.0001) and less SA ( p = 0.003) and trended toward fewer minutes of moderate-to-vigorous PA (MVPA) ( p = 0.08) than non-DS youth. No race or sex differences in MVPA were detected in those with DS, unlike non-DS. After additional adjustment for pubertal status, the relationship between MVPA and VFAT approached significance ( p = 0.06), whereas the relationships of LPA and SA with VFAT were maintained ( p ≤ 0.0001 for both). CONCLUSION: Youth with DS engage in more LPA compared with non-DS, which, in typically developing populations, can confer a more favorable weight status. Increasing the opportunity for youth with DS to engage in LPA as part of their activities of daily living may offer a viable strategy for achieving healthy weight when barriers restrict pursuit of more vigorous PA.

Prevalence of unsuspected abnormal echocardiograms in adolescents with down syndrome.

The purpose of this article is to describe the prevalence of cardiac disease previously undiagnosed in healthy asymptomatic children and adolescents with Down syndrome (DS). Subjects with DS ages 10-20 years were recruited from two sites, the Children's Hospital of Philadelphia (Philadelphia, PA) and Children's National Health System (Washington, DC) for a cross-sectional study of body composition and cardiometabolic risk. Echocardiographic and clinical data were collected from patients enrolled in the parent study of cardiometabolic risk. Nine (6%) new cardiac diagnoses were identified out of 149 eligible patients. All new findings resulted in outpatient referrals to pediatric cardiology. Current guidelines recommend screening all newborns with DS for congenital heart disease. Older patients with DS may benefit from rescreening.

Cross-Sectional Study of Arterial Stiffness in Adolescents with Down Syndrome.

OBJECTIVES: To test whether youth with Down syndrome have aortic stiffness indices, as measured by pulse wave velocity (PWV), that differ from youth without Down syndrome and to compare reference-based age-adjusted (age-PWV-Z) and height-adjusted (Ht-PWV-Z) in youth with and without Down syndrome. STUDY DESIGN: Cross-sectional study of PWV in 129 adolescents with Down syndrome and 97 youth of comparable age, sex, race/ethnicity, and body mass index (BMI). PWV, age-PWV-Z, and Ht-PWV-Z were compared. Regression models were developed to test for associations with PWV. RESULTS: Youth with Down syndrome and controls were comparable in BMI-Z (1.4 [-1.5 to 2.8] vs 1.2 [-2.0 to 2.8], P = .57) but not Ht-Z (-2.3 [-4.7 to 0.8] vs 0.4 [-2.0 to 2.6], P < .0001). PWV (m/s, 5.0 [3.1-7.9] vs 5.0 [3.6-8.0], P = .5) and mean arterial pressure (MAP, mm Hg) (78 [61-102] vs 74 [64-97], P = .09) were not different between groups. In adjusted analyses confined to Down syndrome, PWV was associated only with BMI, but not age, black race, or MAP (R2 = 0.11). In contrast, BMI, age, black race, and MAP were all positively associated with and better explained PWV in controls (R2 = 0.50). PWV was not associated with height in youth with or without Down syndrome. Although age-PWV-Z was not different in Down syndrome (-0.36 [-2.93 to 3.49]) vs -0.15 [-2.32 to 3.22]), Ht-PWV-Z was greater in Down syndrome (0.32 [-2.28 to 4.07] vs -0.08 [-2.64 to 2.64], P = .002), and Ht-PWV-Z was greater than age-PWV-Z in Down syndrome (P < .0001). CONCLUSIONS: The lack of relationship of PWV, an independent predictor of adult cardiovascular events, with its traditional determinants including MAP suggests Down syndrome-specific phenomena may alter such relationships in this population. In youth with Down syndrome, Ht-adjusted PWV may overestimate aortic stiffness. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01821300.

Relationships of Body Composition to Cardiac Structure and Function in Adolescents With Down Syndrome are Different than in Adolescents Without Down Syndrome.

Median survival in Down syndrome (DS) is 60 years, but cardiovascular disease risk and its markers such as left ventricular mass (LVM) have received limited attention. In youth, LVM is typically scaled to height2.7 as a surrogate for lean body mass (LBM), the strongest predictor of LVM, but whether this algorithm applies to DS, a condition which features short stature, is unknown. To examine the relationships of LVM and function with height, LBM, and moderate-to-vigorous physical activity(MVPA) in DS, DS youth aged 10-20 years, and age-, sex-, BMI-, race-matched nonDS controls underwent echocardiography for LVM, ejection fraction (EF), and left ventricular diastolic function (measured as E/E'); dual-energy X-ray absorptiometry (DXA)-measured LBM; accelerometry for MVPA. (DS vs. nonDS median [min-max]): DS had lower height (cm) (144.5 [116.7-170.3] vs. 163.3 [134.8-186.7]; p < 0.0001); LBM (kg) (33.48 [14.5-62.3] vs 41.8 [18.07-72.46], p < 0.0001); and LVM (g) (68.3 [32.1-135] vs 94.0 [43.9-164.6], p < 0.0001); similar EF (%) (65 [54-77] vs 64 [53-77], p = 0.59); and higher E/E' (8.41 [5.54-21.4] vs 5.81 [3.44-9.56], p < 0.0001). In height2.7-adjusted models, LVM was lower in DS (ß = - 7.7, p = 0.02). With adjustment for LBM, LVM was even lower in DS (ß = - 15.1, p < 0.0001), a finding not explained by MVPA. E/E' remained higher in DS after adjustment for age, height, HR, SBP, and BMI (ß = 2.6, p < 0.0001). DS was associated with stiffer left ventricles and lower LVM, the latter magnified with LBM adjustment. Scaling to height2.7, the traditional approach for assessing LVM in youth, may underestimate LVM differences in DS. Whether lower LVM and diastolic function are intrinsic to DS, pathologic, or protective remains unknown.Clinical Trial Registration: NCT01821300.

Effectiveness of early lens extraction for the treatment of primary angle-closure glaucoma (EAGLE): a randomised controlled trial.

BACKGROUND: Primary angle-closure glaucoma is a leading cause of irreversible blindness worldwide. In early-stage disease, intraocular pressure is raised without visual loss. Because the crystalline lens has a major mechanistic role, lens extraction might be a useful initial treatment. METHODS: From Jan 8, 2009, to Dec 28, 2011, we enrolled patients from 30 hospital eye services in five countries. Randomisation was done by a web-based application. Patients were assigned to undergo clear-lens extraction or receive standard care with laser peripheral iridotomy and topical medical treatment. Eligible patients were aged 50 years or older, did not have cataracts, and had newly diagnosed primary angle closure with intraocular pressure 30 mm Hg or greater or primary angle-closure glaucoma. The co-primary endpoints were patient-reported health status, intraocular pressure, and incremental cost-effectiveness ratio per quality-adjusted life-year gained 36 months after treatment. Analysis was by intention to treat. This study is registered, number ISRCTN44464607. FINDINGS: Of 419 participants enrolled, 155 had primary angle closure and 263 primary angle-closure glaucoma. 208 were assigned to clear-lens extraction and 211 to standard care, of whom 351 (84%) had complete data on health status and 366 (87%) on intraocular pressure. The mean health status score (0·87 [SD 0·12]), assessed with the European Quality of Life-5 Dimensions questionnaire, was 0·052 higher (95% CI 0·015-0·088, p=0·005) and mean intraocular pressure (16·6 [SD 3·5] mm Hg) 1·18 mm Hg lower (95% CI -1·99 to -0·38, p=0·004) after clear-lens extraction than after standard care. The incremental cost-effectiveness ratio was £14 284 for initial lens extraction versus standard care. Irreversible loss of vision occurred in one participant who underwent clear-lens extraction and three who received standard care. No patients had serious adverse events. INTERPRETATION: Clear-lens extraction showed greater efficacy and was more cost-effective than laser peripheral iridotomy, and should be considered as an option for first-line treatment. FUNDING: Medical Research Council.

Diffusion tensor imaging in parkinsonian syndromes: a systematic review and meta-analysis.

OBJECTIVES: We performed a systematic review to assess alterations in measures of diffusion tensor imaging (DTI) in parkinsonian syndromes, exploring the potential role of DTI in diagnosis and as a candidate biomarker. METHODS: We searched EMBASE and Medline databases for DTI studies comparing parkinsonian syndromes or related dementias with controls or another defined parkinsonian syndrome. Key details for each study regarding participants, imaging methods, and results were extracted. Estimates were pooled, where appropriate, by random-effects meta-analysis. RESULTS: Of 333 results, we identified 43 studies suitable for inclusion (958 patients, 764 controls). DTI measures detected alterations in all parkinsonian syndromes, with distribution varying differentially with disease type. Nine studies were included in a meta-analysis of the substantia nigra in Parkinson disease. A notable effect size was found for lowered fractional anisotropy in the substantia nigra for patients with Parkinson disease vs controls (-0.639, 95% confidence interval -0.860 to -0.417, p < 0.0001). CONCLUSION: DTI may be a promising biomarker in parkinsonian syndromes and have a future role in differential diagnosis. Larger cohort studies are required to investigate some encouraging preliminary findings. Given the complexity of the parkinsonian syndromes, it is likely that any potential DTI biomarker would be used in combination with other relevant biomarkers.