Evaluation of a bovine antibody test for diagnosing Mycobacterium avium complex in patients with cystic fibrosis.

Pediatr Pulmonol. 2016 Sep 20;

Authors: Qvist T, Pressler T, Katzenstein TL, Høiby N, Collins MT

Abstract
INTRODUCTION: The aim of this study was to test a commercial bovine enzyme-linked immunosorbent assay for investigating antibody activity against Mycobacterium avium complex.
METHODS: All patients at the Copenhagen Cystic Fibrosis (CF) Center who had culture for nontuberculous mycobacteria performed were included. A commercially available antibody test used in veterinary medicine, was adjusted for human use, and applied to patient sera in a cross sectional test. The test positivity threshold was determined using a receiver operating curve (ROC). A longitudinal analysis of antibody kinetics before and after culture conversion was performed in case patients.
RESULTS: Out of 286 included subjects, six had clinical M. avium complex pulmonary disease at the time of sera sampling. These patients presented with higher antibody test values (P-value <0.01). A test cut point of 0.78 was chosen, corresponding to a sensitivity of 100% (54-100), specificity of 66% (60-72), a positive predictive value of 6% (2-13), and negative predictive value of 100% (98-100).
CONCLUSION: While not suited for direct diagnosis of M. avium complex due to a high number of false positive subjects, the assay proved useful at ruling out pulmonary disease. Screening sera from patients with CF could guide clinicians to focus attention on patients at higher risk of M. avium complex pulmonary disease. Pediatr Pulmonol. 2016; 9999:XX-XX. © 2016 Wiley Periodicals, Inc.

PMID: 27648735 [PubMed - as supplied by publisher]

Impact of the shape of the needle tip on the efficacy of flushing implantable port chambers.

J Vasc Access. 2016 Aug 18;:0

Authors: Guiffant G, Dupont C, Merckx J

Abstract
INTRODUCTION: To follow international guidelines and protect healthcare workers from needle stick injuries, manufacturers now provide safety non-coring needles.
METHODS: Numerical simulations show the potential efficacy of infusion and flushing flow in straight and curved side wall port chambers from a beveled non-coring needle (BNCN) or a bevel-free cannula (BFC).
RESULTS: In straight and curved side wall port chambers, the stream of flow with a BNCN is determined by the direction of the bevel, whereas the outlet stream from a BFC leads to a cylindrical symmetric flow. This, along with the position of the BFC impacts the wall shear rate of the port chamber, and the hydraulic resistance within the chamber.
DISCUSSION: This last factor has never been the subject of extensive hydrodynamic study. Caregiver safety and patient comfort are paramount but physics show that the shape of the needle tip affects the hydrodynamics of the injected flow.
CONCLUSIONS: The presence of a bevel at the needle tip is a key factor for ensuring efficient flushing of the port. The absence of a bevel may increase hydraulic resistance and deposits in the port chamber. Implantable port flushing protocols must take this notion into account if the patency of port chambers is to be maintained. The clinical impact of this study has yet to be determined.

PMID: 27646926 [PubMed - as supplied by publisher]

Palmar wrinkling: Identification of a peculiar pattern at incident light dermoscopy with confocal microscopy correlation.

J Am Acad Dermatol. 2016 Oct;75(4):e143-e145

Authors: Lacarrubba F, Verzì AE, Leonardi S, Trovato G, Micali G

PMID: 27646757 [PubMed - as supplied by publisher]

The Mucus Barrier to Inhaled Gene Therapy.

Mol Ther. 2016 Sep 20;

Authors: Duncan GA, Jung J, Hanes J, Soo Suk J

Abstract
Recent evidence suggests that the airway mucus gel layer may be impermeable to the viral and synthetic gene vectors used in past inhaled gene therapy clinical trials for diseases like cystic fibrosis. These findings support the logic that inhaled gene vectors that are incapable of penetrating the mucus barrier are unlikely to provide meaningful benefit to patients. In this review, we discuss the biochemical and biophysical features of mucus that contribute its barrier function, and how these barrier properties may be reinforced in patients with lung disease. We next review biophysical techniques used to assess the potential ability of gene vectors to penetrate airway mucus. Finally, we provide new data that suggest that fresh human airway mucus should be used to test the penetration rates of gene vectors. The physiological barrier properties of spontaneously expectorated CF sputum remained intact up to 24 hours after collection when refrigerated at 4ºC. Conversely, the barrier properties were significanctly altered after freezing and thawing of sputum samples. Gene vectors capable of overcoming the airway mucus barrier hold promise as a means to provide the widespread gene transfer throughout the airway epithelium required to achieve meaningful patient outcomes in inhaled gene therapy clinical trials.

PMID: 27646604 [PubMed - as supplied by publisher]

Lung Clearance Index (LCI) in Patients with Bronchiolitis Obliterans: A Preliminary Report and Comparison to Cystic Fibrosis Patients.

Lung. 2016 Aug 31;

Authors: Gur M, Yaacoby-Bianu K, Ilivitzki A, Bar-Yoseph R, Nir V, Hakim F, Toukan Y, Bentur L

Abstract
INTRODUCTION: Bronchiolitis obliterans (BO) is a chronic airway disease following an insult to the lower respiratory tract. Lung clearance index (LCI) measures ventilation inhomogeneity and has been studied in cystic fibrosis (CF). We aimed to evaluate LCI in BO and to compare it to LCI in CF patients.
METHODS: LCI was measured in BO patients, compared to CF patients, and correlated with spirometry and CT findings.
RESULTS: Twenty BO patients and 26 CF patients (with similar mean age and BMI) underwent evaluation. FEV1 % and FEF25-75 % predicted were significantly lower in the BO group (60.5 ± 17.8 vs. 72.7 ± 20.7, p = 0.041, and 42.8 ± 22.8 vs. 66.4 ± 37.4, p = 0.017, respectively). In both groups, LCI was inversely correlated with FVC %, FEV1 %, and FEF25-75 % predicted. LCI  % was slightly higher (190.4 ± 63.5 vs. 164.9 ± 39.4, p = 0.1) and FRC gas % (measured by multiple breath washout) was significantly higher in the BO group (92.5 ± 35.9 vs. 71.3 ± 18, p = 0.014). The strength of statistical association between the lower FEF25-75 % values and the higher LCI values was stronger in BO patients.
CONCLUSIONS: Similar to CF, LCI may provide estimation of ventilation inhomogeneity in BO. The results indicate greater small airway involvement and air trapping in BO. Further prospective longitudinal studies evaluating the correlation of LCI measurements with multiple clinical and physiological parameters should be performed to assess the clinical benefit of LCI measurement in BO.

PMID: 27645685 [PubMed - as supplied by publisher]

Immediate and catastrophic antibody-mediated rejection in a lung transplant recipient with anti-angiotensin II receptor type 1 and anti-endothelin-1 receptor type A antibodies.

Am J Transplant. 2016 Sep 19;

Authors: Cozzi E, Calabrese F, Schiavon M, Feltracco P, Seveso M, Carollo C, Loy M, Cardillo M, Rea F

Abstract
Preexisting donor-specific anti-HLA antibodies (DSA) have been associated with reduced survival of lung allografts. However, antibodies with specificities other than HLA may have a detrimental role on the lung transplant outcome. A young man with cystic fibrosis underwent lung transplantation with organs from a suitable deceased donor. At the time of transplantation, there were no anti-HLA DSA. During surgery, the patient developed a severe and intractable pulmonary hypertension associated with right ventricle dysfunction which required artero-venous ECMO. Following a brief period of clinical improvement, a rapid deterioration of hemodynamics led to the patient demise on postoperative day 5. Postmortem studies showed that lung specimens taken at the end of surgery were compatible with antibody-mediated rejection (AMR) whilst terminal samples evidenced diffuse capillaritis, blood extravasation, edema and microthrombi, with foci of acute cellular rejection (A3). Immunological investigations demonstrated the presence of preexisting antibodies against the endothelin-1 receptor type A (ETA R) and the angiotensin II receptor type 1 (AT1 R), two of the most potent vasoconstrictors reported to date, whose levels slightly rose following transplantation. These data suggest that preexisting anti-ETA R and anti-AT1 R antibodies may have contributed to the onset of AMR and to the catastrophic clinical course of this patient. This article is protected by copyright. All rights reserved.

PMID: 27640901 [PubMed - as supplied by publisher]

[Causal therapy is available].

MMW Fortschr Med. 2016 Jun 23;158(12):74

Authors: Meißner T

PMID: 27324018 [PubMed - indexed for MEDLINE]

High Penetrance of the PRSS1 A16V Mutation in a Kindred With SPINK1 N34S and CFTR TG11-5T Co-mutations.

Pancreas. 2016 Jan;45(1):e2-4

Authors: Moran RA, Quesada-Vazquez N, Sinha A, de-Madaria E, Singh VK

PMID: 26658045 [PubMed - indexed for MEDLINE]

Onset of persistent pseudomonas aeruginosa infection in children with cystic fibrosis with interval censored data.

BMC Med Res Methodol. 2016;16(1):122

Authors: Wang W, Chen MH, Chiou SH, Lai HC, Wang X, Yan J, Zhang Z

Abstract
BACKGROUND: Persistent Pseudomonas aeruginosa (PPA) infection promotes lung function deterioration in children with cystic fibrosis (CF). Although early CF diagnosis through newborn screening (NBS) has been shown to provide nutritional/growth benefit, it is unclear whether NBS lowers the risk of PPA infection and how the effect of NBS vary with age. Modeling the onset age of PPA infection is challenging because 1) the onset age of PPA infection is interval censored in patient registry data; and 2) some risk factors such as NBS may have time-varying effects.
METHODS: This problem fits into the framework of a recently developed Bayesian dynamic Cox model for interval censored data, where each regression coefficient is allowed to be time-varying to an extent determined by the data.
RESULTS: Application of the methodology to data from the CF Foundation Patient Registry revealed interesting findings. Compared with patients with meconium ileus or diagnosed through signs or symptoms, patients diagnosed through NBS had significantly lower risks of acquiring PPA infection between age 1 and 2 years, and the benefit in survival rate was found to last up to age 4 years. Two cohorts of five years apart were compared. Patients born in cohort 2003-2004 had significantly lower risks of the PPA infections at any age up to 4 years than those born in 1998-1999.
CONCLUSIONS: The study supports benefits of NBS on PPA infection in early childhood. In addition, our analyses demonstrate that patients in the more recent cohort had significantly lower risks of acquiring PPA infection up to age 4 years, which suggests improved CF treatment and care over time.

PMID: 27639560 [PubMed - as supplied by publisher]

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2016/09/18

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2016/09/17

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

8 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2016/09/16

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2016/09/15

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

10 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2016/09/14

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2016/09/13

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Relationship between pulmonary hyperinflation and dyspnoea severity during acute exacerbations of cystic fibrosis.

Respirology. 2016 Sep 11;

Authors: Nicholson TT, Barry PJ, Waterhouse DF, Nolan GM, Mckone EF, Gallagher CG

Abstract
BACKGROUND AND OBJECTIVE: Acute exacerbations of cystic fibrosis (CF) occur frequently throughout the course of the disease. Dyspnoea is the most common and distressing symptom experienced by patients during these episodes. We tested the hypothesis that pulmonary hyperinflation is an important determinant of dyspnoea severity during acute exacerbations.
METHODS: We studied patients during an acute exacerbation of CF. Lung volumes, spirometry and dyspnoea scores were measured at Day 0, Day 7, at the end of treatment (EOT) and 14 days following the EOT.
RESULTS: At the start of treatment, mean residual volume (RV)/total lung capacity (TLC) was 54.9%, which decreased significantly with treatment, as did vital capacity (VC), inspiratory capacity (IC) and dyspnoea scores. IC was the only independent predictor of dyspnoea severity.
CONCLUSION: Our study demonstrates significant improvements in hyperinflation, spirometry and dyspnoea scores with treatment of acute exacerbations of CF. Hyperinflation, rather than airflow limitation, may contribute towards the increased dyspnoea during exacerbations.

PMID: 27614791 [PubMed - as supplied by publisher]

An overview of concept mapping in Dutch mental health care.

Eval Program Plann. 2016 Sep 3;

Authors: Nabitz U, van Randeraad-van der Zee C, Kok I, von Bon-Martens M, Severens P

Abstract
About 25 years ago, concept mapping was introduced in the Netherlands and applied in different fields. A collection of concept mapping projects conducted in the Netherlands was identified, in part in the archive of the Netherlands Institute of Mental Health and Addiction (Trimbos Institute). Some of the 90 identified projects are internationally published. The 90 concept mapping projects reflect the changes in mental health care and can be grouped into 5-year periods and into five typologies. The studies range from conceptualizing the problems of the homeless to the specification of quality indicators for treatment programs for patients with cystic fibrosis. The number of concept mapping projects has varied over time. Growth has been considerable in the last 5 years compared to the previous 5 years. Three case studies are described in detail with 12 characteristics and graphical representations. Concept mapping aligns well with the typical Dutch approach of the "Poldermodel." A broad introduction of concept mapping in European countries in cooperation with other countries, such as the United States and Canada, would strengthen the empirical basis for applying this approach in health care policy, quality, and clinical work.

PMID: 27614364 [PubMed - as supplied by publisher]

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2016/09/11

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Inoculation density and nutrient level determine the formation of mushroom-shaped structures in Pseudomonas aeruginosa biofilms.

Sci Rep. 2016;6:32097

Authors: Ghanbari A, Dehghany J, Schwebs T, Müsken M, Häussler S, Meyer-Hermann M

Abstract
Pseudomonas aeruginosa often colonises immunocompromised patients and the lungs of cystic fibrosis patients. It exhibits resistance to many antibiotics by forming biofilms, which makes it hard to eliminate. P. aeruginosa biofilms form mushroom-shaped structures under certain circumstances. Bacterial motility and the environment affect the eventual mushroom morphology. This study provides an agent-based model for the bacterial dynamics and interactions influencing bacterial biofilm shape. Cell motility in the model relies on recently published experimental data. Our simulations show colony formation by immotile cells. Motile cells escape from a single colony by nutrient chemotaxis and hence no mushroom shape develops. A high number density of non-motile colonies leads to migration of motile cells onto the top of the colonies and formation of mushroom-shaped structures. This model proposes that the formation of mushroom-shaped structures can be predicted by parameters at the time of bacteria inoculation. Depending on nutrient levels and the initial number density of stalks, mushroom-shaped structures only form in a restricted regime. This opens the possibility of early manipulation of spatial pattern formation in bacterial colonies, using environmental factors.

PMID: 27611778 [PubMed - as supplied by publisher]

Different next generation sequencing platforms produce different microbial profiles and diversity in cystic fibrosis sputum.

J Microbiol Methods. 2016 Sep 5;

Authors: Hahn A, Sanyal A, Perez G, Colberg-Poley AM, Campos J, Rose M, Pérez-Losada M

Abstract
BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disease characterized by recurrent lung infections. Studies of the lung microbiome have shown an association between decreasing diversity and progressive disease. 454 pyrosequencing has frequently been used to study the lung microbiome in CF, but will no longer be supported. We sought to identify the benefits and drawbacks of using two state-of-the-art next generation sequencing (NGS) platforms, MiSeq and PacBio RSII, to characterize the CF lung microbiome. Each has its advantages and limitations.
METHODS: Twelve samples of extracted bacterial DNA were sequenced on both MiSeq and PacBio NGS platforms. DNA was amplified for the V4 region of the 16S rRNA gene and libraries were sequenced on the MiSeq sequencing platform, while the full 16S rRNA gene was sequenced on the PacBio RSII sequencing platform. Raw FASTQ files generated by the MiSeq and PacBio platforms were processed in mothur v1.35.1.
RESULTS: There was extreme discordance in alpha-diversity of the CF lung microbiome when using the two platforms. Because of its depth of coverage, sequencing of the 16S rRNA V4 gene region using MiSeq allowed for the observation of many more operational taxonomic units (OTUs) and higher Chao1 and Shannon indices than the PacBio RSII. Interestingly, several patients in our cohort had Escherichia, an unusual pathogen in CF. Also, likely because of its coverage of the complete 16S rRNA gene, only PacBio RSII was able to identify Burkholderia, an important CF pathogen.
CONCLUSION: When comparing microbiome diversity in clinical samples from CF patients using 16S sequences, MiSeq and PacBio NGS platforms may generate different results in microbial community composition and structure. It may be necessary to use different platforms when trying to correctly identify dominant pathogens versus measuring alpha-diversity estimates, and it would be important to use the same platform for comparisons to minimize errors in interpretation.

PMID: 27609714 [PubMed - as supplied by publisher]