A novel surfactant protein C gene mutation associated with progressive respiratory failure in infancy.

Pediatr Pulmonol. 2017 Jan;52(1):57-68

Authors: Litao MK, Hayes D, Chiwane S, Nogee LM, Kurland G, Guglani L

Abstract
Mutations of the Surfactant Protein C (SPC) gene (SFTPC) have been associated with childhood interstitial lung disease (chILD) with variable age of onset, severity of lung disease, and outcomes. We report a novel mutation in SFTPC [c.435G->A, p.(Gln145)] that was associated with onset of symptoms in early infancy, progressive respiratory failure with need for prolonged mechanical ventilatory support, and eventual lung transplant at 1 year of age. While the mutation was not predicted to alter the amino acid sequence of the SP-C precursor protein, analysis of SP-C transcripts demonstrated skipping of exon 4. Because of limited data about the outcomes of infants with SFTPC mutations, we conducted a systematic review of all the SFTPC mutations reported in the literature in order to define their presenting features, clinical and radiologic features, and outcomes. Further advances in our understanding of chILD and creation of an international registry will help to track these patients and their outcomes. Pediatr Pulmonol. 2017;52:57-68. © 2016 Wiley Periodicals, Inc.

PMID: 27362365 [PubMed - indexed for MEDLINE]

A de novo interstitial deletion of 7q31.2q31.31 identified in a girl with developmental delay and hearing loss.

Am J Med Genet C Semin Med Genet. 2016 Jun;172(2):102-8

Authors: Zhao J, Noon SE, Krantz ID, Wu Y

Abstract
We report on a 4-year-old female who presented with unilateral sensorineural hearing loss and a concern for developmental delay. A genome-wide SNP array analysis was performed and revealed a de novo 3.2 Mb interstitial deletion of chromosome 7q31.2q31.31. This region contains thirteen protein-encoding genes. It is unknown whether haploinsufficiency of any of these genes is responsible for the clinical features of our patient. We reviewed, the clinical phenotype of a previously published 7q31.3 deletion patient and 18 additional patients with overlapping 7q31 deletions listed in the DECIPHER database. The most consistent feature in these patients and our proband is delayed speech and language development. Hearing loss is presented both in our proband and the published 7q31.3 patient. Our study suggests that a small region on chromosome 7q31.3 encompassing four genes, CFTR, CTTNBP2, NAA38, and ANKRD7, may represent a new locus for congenital hearing loss and/or speech development. © 2016 Wiley Periodicals, Inc.

PMID: 27075776 [PubMed - indexed for MEDLINE]

A Link Between a Common Mutation in CFTR and Impaired Innate and Adaptive Viral Defence.

J Infect Dis. 2017 Sep 09;:

Authors: Svedin E, Utorova R, Hühn MH, Larsson P, Stone VM, Garimella M, Lind K, Hägglöf T, Pincikova T, Laitinen O, McInerney GM, Scholte B, Hjelte L, Karlsson MCI, Flodström-Tullberg M

Abstract
Acute respiratory virus infections predispose the Cystic Fibrosis (CF) lung to chronic bacterial colonization, which contributes to high mortality. For reasons unknown, respiratory virus infections have a prolonged duration in CF. Here, we demonstrate that mice carrying the most frequent CFTR mutation in humans, F508del, show increased morbidity and mortality following infection with a common human enterovirus. F508del mice demonstrated impaired viral clearance, a slower type I interferon response and delayed production of virus neutralizing antibodies. While the F508 mice had a normal immune cell repertoire, unchanged serum immunoglobulin concentrations and an intact immune response to a T cell-independent antigen, their response to a T cell-dependent antigen was significantly delayed. Our studies reveal a novel function for CFTR in antiviral immunity and demonstrate that the F508 mutation in cftr is coupled to an impaired adaptive immune response. This important insight could open up new approaches for patient care and treatment.

PMID: 28968805 [PubMed - as supplied by publisher]

[Profile of gastrointestinal diseases in a pediatric gastroenterology center in Colombia: 15 years of follow-up].

Biomedica. 2017 Sep 01;37(3):315-323

Authors: Daza W, Dadan S, Higuera M

Abstract
INTRODUCTION: The profile of gastrointestinal diseases is constantly changing globally and locally affecting suspected diagnosis and medical methods.
OBJECTIVE: To establish the main diagnoses in a gastroenterology, hepatology, and pediatric nutrition unit in Bogota between 2009 and 2013, and to compare with findings from the same unit during the two prior five-year periods (1997 to 2006).
MATERIALS AND METHODS: We conducted a retrospective descriptive study. Medical records were reviewed to extract diagnoses. Data from the two previous five-year periods were taken from institutional records. A univariate analysis was performed, along with calculation of absolute and relative frequencies for qualitative variables, and central tendency and dispersion measures for quantitative variables.
RESULTS: The study collected the diagnoses of 1,171 patients, 51.8% (607) of whom were male, and 64% (753/1171), under five years of age. The main diagnoses were: constipation (33.9%), food allergy (23.5%), eating disorders (5.5%), gastroesophageal reflux disease (4.1%), peptic ulcer disease (4.1%), persistent diarrhea (3.8%) and cystic fibrosis (3.4%). Upon comparing this period with the two previous ones, we observed that peptic ulcer disease decreased while constipation, which was in the second position, rose to the first place. Food allergy, not registered within the first ten diagnoses in previous periods, appeared during this last period.
CONCLUSIONS: During the last five years, constipation was the first gastrointestinal diagnosis followed by food allergy, in agreement with the global trend. It is essential, therefore, to apply diagnostic algorithms, timely treatment, and prevention.

PMID: 28968008 [PubMed - in process]

Endoplasmic Reticulum Stress Is a Danger Signal Promoting Innate Inflammatory Responses in Bronchial Epithelial Cells.

J Innate Immun. 2016;8(5):464-78

Authors: Mijošek V, Lasitschka F, Warth A, Zabeck H, Dalpke AH, Weitnauer M

Abstract
Endoplasmic reticulum (ER) stress is associated with chronic pulmonary inflammatory diseases. We hypothesized that the combined activation of both Toll-like receptor (TLR) signaling and ER stress might increase inflammatory reactions in otherwise tolerant airway epithelial cells. Indeed, ER stress resulted in an increased response of BEAS-2B and human primary bronchial epithelial cells to pathogen-associated molecular pattern stimulation with respect to IL6 and IL8 production. ER stress elevated p38 and ERK MAP kinase activation, and pharmacological inhibition of these kinases could inhibit the boosting effect. Knockdown of unfolded protein response signaling indicated that mainly PERK and ATF6 were responsible for the synergistic activity. Specifically, PERK and ATF6 mediated increased MAPK activation, which is needed for effective cytokine secretion. We conclude that within airway epithelial cells the combined activation of TLR signaling and ER stress-mediated MAPK activation results in synergistic proinflammatory activity. We speculate that ER stress, present in various chronic pulmonary diseases, boosts TLR signaling and therefore proinflammatory cytokine production, thus acting as a costimulatory danger signal.

PMID: 27423489 [PubMed - indexed for MEDLINE]

Exercise performance and quality of life in children with cystic fibrosis and mildly impaired lung function: relation with antibiotic treatments and hospitalization.

Eur J Pediatr. 2017 Sep 30;:

Authors: Vandekerckhove K, Keyzer M, Cornette J, Coomans I, Pyl F, De Baets F, Schelstraete P, Haerynck F, De Wolf D, Van Daele S, Boone J

Abstract
This study evaluates the impact of antibiotic treatments and hospitalization on exercise performance and health-related quality of life (QOL) in children with mild cystic fibrosis (CF) lung disease. Forty-seven children between 7 and 17 years with mild CF underwent a maximal exercise test including spiro-ergometry and filled out a QOL-questionnaire (PedsQL™). Amount of antibiotic treatments (AB) and hospitalization days in the last 3 years were reviewed. FEV1% was mildly decreased (91.7 ± 17.9 L/min, p = 0.02). Maximal oxygen consumption (VO2max), test duration and anaerobic threshold were lower compared to a control population (VO2max% 94 ± 15 vs 103 ± 13, p = 0.009). FEV1% correlated with AB and hospitalization episodes in the last year and 3 years before testing, VO2max% only correlated with AB in the last 3 years. Domains of school functioning and emotional functioning were low. Children with higher VO2max% and less AB in the last 3 years had better physical health. Physical health and school functioning were negatively correlated with hospitalization days in the last year.
CONCLUSION: Patients with mild CF lung disease have good exercise performance although still lower than the normal population. VO2max% is affected by number of antibiotic treatments over a longer period. There is an impact of hospitalization days on quality of life. What is Known: • Children with CF have lower exercise performance; there is an association between hospitalization frequency and exercise performance • Quality of life is diminished in children with CF and influenced by respiratory infections What is New: • Even patients with mild CF lung disease have lower maximal exercise performance (VO 2 max) and a lower anaerobic threshold; VO 2 max is lower in children who had more antibiotic treatments in the last 3 years • School and emotional functioning are diminished in children with mild CF lung disease; hospitalization is negatively correlated with school functioning and physical functioning.

PMID: 28965267 [PubMed - as supplied by publisher]

Burkholderia cepacia complex in cystic fibrosis in a Brazilian reference center.

Med Microbiol Immunol. 2017 Sep 30;:

Authors: Dentini P, Marson FAL, Bonadia LC, Bertuzzo CS, Ribeiro AF, Levy CE, Ribeiro JD

Abstract
The Burkholderia cepacia complex (BCC) can cause a severe decline in lung function in cystic fibrosis (CF). Our objective was to determine the BCC prevalence and to evaluate its clinical impact on CF. Clinical and laboratory variables were determined for CF patients with BCC (Group-A = 50 patients) and without BCC (Group-B = 134 patients). The microorganisms were identified by biochemical tests, the Vitek2(®)Compact test, recA-PCR and recA-nested-PCR with species-specific primers and DNA sequencing. The patients were evaluated by the Shwachman-Kulczycki score (SKCS), Bhalla score (BS), spirometry and body mass index (BMI). The BCC prevalence was 22.5%. The most common species were Burkholderia multivorans (30%), Burkholderia cepacia (24%), Burkholderia cenocepacia IIIA (10%), B. cenocepacia IIIB (2%) and Burkholderia vietnamiensis (2%). There was difference between the groups in nutritional status (p = 0.02) and general activity (p = 0.026). There was difference in total BS points (p = 0.04) and the following parameters: bronchiectasis severity (p = 0.007), peribronchial thickening (p = 0.013), bronchiectasis extent (p = 0.01) and general aspects of the affected bronchial zone (p = 0.02). The respiratory disorder classifications were as follows: obstructive-4.8% (Group-A) and 23.8% (Group-B); restrictive-9.5% (Group-A and Group-B); obstructive + restrictive-19% (Group-A) and 1.6% (Group-B); and obstructive + restrictive with a decreased forced expiratory flow-47.6% (Group-A) and 30.2% (Group-B) (p = 0.02). Nutritional status was a minor contributing factor to weight, height and BMI in the Group-A (p = 0.02). The BCC prevalence, particularly the prevalence of B. multivorans, was higher in this study. The SKCS, BS, spirometry and nutritional status results showed that BCC has a negative impact on clinical status. Phenotypic methods are useful for the identification of presumptive BCC. The Vitek2(®)Compact test showed accuracy in BCC identification. PCR, nested-PCR, and recA sequencing showed specificity in BCC species identification.

PMID: 28965239 [PubMed - as supplied by publisher]

Physicochemical stability and aerosolization performance of dry powder inhalation system containing ciprofloxacin hydrochloride.

J Pharm Biomed Anal. 2017 Sep 22;148:73-79

Authors: Karimi K, Katona G, Csóka I, Ambrus R

Abstract
Antibiotic delivery in form of dry powder inhalation has been studied for possible clinical treatment of respiratory tract infection in the recent years. Dry powder inhalation of ciprofloxacin hydrochloride (CIP) assures local antibacterial activity and comfort of easy application. The aim of this work was to test the stability of co-spray-dried CIP in carrier free system. Since the microparticles in the dry powder system are amorphous and do not contain any stabilizer, the effects of temperature and relative humidity (RH) on the physicochemical properties and aerosolization behavior are very important. Therefore investigation of the role of excipients (such as polyvinyl alcohol (PVA), l-leucine (LEU) and hydroxypropyl-beta-cyclodextrin (CD)) on physicochemical stability and aerosolization performance is essential element prior designing the final dosage form. Stability tests (stress and accelerated) were performed at 40±2°C and 75±5% RH during 6 months. Particle characterization and size measurement - as the most important parameters in aerodynamic behavior - were done by the laser diffraction method, the surface morphology of microparticles was evaluated by scanning electron microscopy (SEM). The physiochemical properties of microparticles were investigated by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). The resulting aerodynamic behavior of microparticles was studied by Andersen cascade impactor. The overall stability results (against RH and temperature) showed that microparticles containing CIP and LEU alone and in combination with the other excipients were more stable than those containing PVA or CD alone. In relation to fine particle fraction and mass median aerodynamic diameter (determining the aerosolization parameters), it was found that the particle size and particle shape did not show significant changes after the storage. Among the excipients LEU was found to have many advantages, including relatively simple formulation, enhanced aerosolization behaviour, convenient portability and inherently improved stability. Such a composition may serve as an innovative drug delivery system for the local treatment of respiratory tract infection and cystic fibrosis.

PMID: 28965047 [PubMed - as supplied by publisher]

Real life practice of sweat testing in Europe.

J Cyst Fibros. 2017 Sep 27;:

Authors: Cirilli N, Southern KW, Buzzetti R, Barben J, Nährlich L, Munck A, Wilschanski M, De Boeck K, Derichs N, of the ECFS Diagnostic Network Working Group

Abstract
Evidence based guidelines exist for sweat testing, which remains a key component of a diagnosis of cystic fibrosis (CF), especially following newborn bloodspot screening (NBS). There are emerging challenges with respect to maintaining a valid sweat test service, notably a smaller number of sweat tests ordered in regions with established NBS programmes where Pediatricians refer less children for sweat testing, younger patients and equipment becoming obsolete. The ECFS Diagnostic Network Working Group has undertaken a comprehensive survey to better define sweat test practice across Europe. The survey was completed by 136 European respondents representing a CF center or laboratory providing a sweat test service (65% from regions with NBS for CF). There was considerable variance in practice, often not consistent with guidelines. In particular collection of sweat from two sites was rarely reported in European centres in contrast to US guidelines. There was a range of different references quoted for cut-off for both a positive and intermediate test. Most responses suggest cost is becoming an increasing issue and is not sufficiently reimbursed. This work will inform best practice guidelines and resources to sustain and improve sweat testing in Europe.

PMID: 28964647 [PubMed - as supplied by publisher]

Pediatric lung transplantation.

Semin Pediatr Surg. 2017 Aug;26(4):213-216

Authors: Bryant R, Morales D, Schecter M

Abstract
Pediatric lung transplantation is a highly specialized clinical endeavor. Since the late 1980's, there have only been slightly more than 2200 implants reported to the International Society for Heart and Lung transplantation registry. This review will discuss the historical aspects of pediatric lung transplantation. It will familiarize the reader with the current indications for transplant and the referral and listing process. The current state of lung assist devices as a bridge to pediatric lung transplantation is discussed in addition to the technical aspects of the transplant procedure. Finally, posttransplant outcomes, including anticipated morbidity and the role of retransplantation, are clarified.

PMID: 28964476 [PubMed - in process]

Incidental late diagnosis of cystic fibrosis following AH1N1 influenza virus pneumonia: a case report.

J Med Case Rep. 2017 Oct 01;11(1):278

Authors: Iadevaia C, Iacotucci P, Carnovale V, Calabrese C, Rea G, Ferrara N, Perrotta F, Mazzarella G, Bianco A

Abstract
BACKGROUND: Cystic fibrosis is an autosomal recessive disorder characterized by chronic progressive multisystem involvement. AH1N1 virus infections caused classic influenza symptoms in the majority of cystic fibrosis patients while others experienced severe outcomes.
CASE PRESENTATION: We report a case of late incidental cystic fibrosis diagnosis in a young Caucasian man suffering from respiratory failure following infection due to AH1N1 influenza virus. The patient was admitted to our department with fever, cough, and dyspnea at rest unresponsive to antibiotics CONCLUSIONS: Late diagnosis of cystic fibrosis in uncommon. This report highlights the importance of early cystic fibrosis diagnosis to minimize risk of occurrence of potential life-threatening complications.

PMID: 28964265 [PubMed - in process]

Risk factors for multidrug-resistant pathogens in bronchiectasis exacerbations.

BMC Infect Dis. 2017 Sep 30;17(1):659

Authors: Menéndez R, Méndez R, Polverino E, Rosales-Mayor E, Amara-Elori I, Reyes S, Sahuquillo-Arce JM, Fernández-Barat L, Alcaraz V, Torres A

Abstract
BACKGROUND: Non-cystic fibrosis bronchiectasis is a chronic structural lung condition that courses with recurrent infectious exacerbations that lead to frequent antibiotic treatment making this population more susceptible to acquire pathogens with antibiotic resistance. We aimed to investigate risk factors associated with isolation of multidrug-resistant pathogens in bronchiectasis exacerbations.
METHODS: A prospective observational study was conducted in two tertiary-care hospitals, enrolling patients when first exacerbation appeared. Multidrug-resistance was determined according to European Centre of Diseases Prevention and Control classification.
RESULTS: Two hundred thirty three exacerbations were included and microorganisms were isolated in 159 episodes. Multidrug-resistant pathogens were found in 20.1% episodes: Pseudomonas aeruginosa (48.5%), methicillin-resistant Staphylococcus aureus (18.2%) and Extended spectrum betalactamase + Enterobacteriaceae (6.1%), and they were more frequent in exacerbations requiring hospitalization (24.5% vs. 10.2%, p: 0.016). Three independent multidrug-resistant risk factors were found: chronic renal disease (Odds ratio (OR), 7.60, 95% CI 1.92-30.09), hospitalization in the previous year (OR, 3.88 95% CI 1.37-11.02) and prior multidrug-resistant isolation (OR, 5.58, 95% CI 2.02-15.46). The proportion of multidrug-resistant in the 233 exacerbations was as follows: 3.9% in patients without risk factors, 12.6% in those with 1 factor and 53.6% if ≥2 risk factors.
CONCLUSIONS: Hospitalization in the previous year, chronic renal disease, and prior multidrug-resistant isolation are risk factors for identification multidrug-resistant pathogens in exacerbations. This information may assist clinicians in choosing empirical antibiotics in daily clinical practice.

PMID: 28964261 [PubMed - in process]

[Chronic Pseudomonas aeruginosa airway colonization in cystic fibrosis patients : Prevention concepts].

Internist (Berl). 2017 Sep 29;:

Authors: Dittrich AM

Abstract
Pseudomonas aeruginosa (PsA) is a hallmark pathogen of the lung disease in cystic fibrosis (CF) patients. Chronic PsA colonization is a central factor in the course of CF lung disease. PsA contributes considerably to morbidity and mortality, and also has a significant impact on quality of life and the costs of CF treatment. Prevention of chronic colonization has therefore been a major goal in the treatment of CF patients for many years now. In the present article, studies are presented which suggest that prevention of chronic colonization can be achieved. Approaches to prevent chronic PsA colonization are critically evaluated and recommendations for preventative approaches are generated from this discussion.

PMID: 28963697 [PubMed - as supplied by publisher]

Epithelial Chloride Transport by CFTR Requires TMEM16A.

Sci Rep. 2017 Sep 29;7(1):12397

Authors: Benedetto R, Ousingsawat J, Wanitchakool P, Zhang Y, Holtzman MJ, Amaral M, Rock JR, Schreiber R, Kunzelmann K

Abstract
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is the secretory chloride/bicarbonate channel in airways and intestine that is activated through ATP binding and phosphorylation by protein kinase A, but fails to operate in cystic fibrosis (CF). TMEM16A (also known as anoctamin 1, ANO1) is thought to function as the Ca(2+) activated secretory chloride channel independent of CFTR. Here we report that tissue specific knockout of the TMEM16A gene in mouse intestine and airways not only eliminates Ca(2+)-activated Cl(-) currents, but unexpectedly also abrogates CFTR-mediated Cl(-) secretion and completely abolishes cAMP-activated whole cell currents. The data demonstrate fundamentally new roles of TMEM16A in differentiated epithelial cells: TMEM16A provides a mechanism for enhanced ER Ca(2+) store release, possibly engaging Store Operated cAMP Signaling (SOcAMPS) and activating Ca(2+) regulated adenylyl cyclases. TMEM16A is shown to be essential for proper activation and membrane expression of CFTR. This intimate regulatory relationship is the cause for the functional overlap of CFTR and Ca(2+)-dependent chloride transport.

PMID: 28963502 [PubMed - in process]

Rifampicin potentiation of aminoglycoside activity against cystic fibrosis isolates of Pseudomonas aeruginosa.

J Antimicrob Chemother. 2017 Sep 05;:

Authors: Mikalauskas A, Parkins MD, Poole K

Abstract
Objectives: Rifampicin potentiates the activity of aminoglycosides (AGs) versus Pseudomonas aeruginosa by targeting the AmgRS two-component system. In this study we examine the impact of rifampicin on the AG susceptibility of cystic fibrosis (CF) lung isolates of P. aeruginosa and the contribution of AmgRS to AG resistance in these isolates.
Methods: amgR deletion derivatives of clinical isolates were constructed using standard gene replacement technology. Susceptibility to AGs ± rifampicin (at ½ MIC) was assessed using a serial 2-fold dilution assay.
Results: Rifampicin showed a variable ability to potentiate AG activity versus the CF isolates, enhancing AG susceptibility between 2- and 128-fold. Most strains showed potentiation for at least two AGs, with only a few strains showing no AG potentiation by rifampicin. Notably, loss of amgR increased AG susceptibility although rifampicin potentiation of AG activity was still observed in the Δ amgR derivatives.
Conclusions: AmgRS contributes to AG resistance in CF isolates of P. aeruginosa and rifampicin shows a variable ability to potentiate AG activity against these, highlighting the complexity of AG resistance in such isolates.

PMID: 28961705 [PubMed - as supplied by publisher]

Powerful tools for genetic modification: Advances in gene editing.

Pediatr Pulmonol. 2017 Sep 27;:

Authors: Roesch EA, Drumm ML

Abstract
Recent discoveries and technical advances in genetic engineering, methods called gene or genome editing, provide hope for repairing genes that cause diseases like cystic fibrosis (CF) or otherwise altering a gene for therapeutic benefit. There are both hopes and hurdles with these technologies, with new ideas emerging almost daily. Initial studies using intestinal organoid cultures carrying the common, F508del mutation have shown that gene editing by CRISPR/Cas9 can convert cells lacking CFTR function to cells with normal channel function, providing a precedent that this technology can be harnessed for CF. While this is an important precedent, the challenges that remain are not trivial. A logistical issue for this and many other genetic diseases is genetic heterogeneity. Approximately, 2000 mutations associated with CF have been found in CFTR, the gene responsible for CF, and thus a feasible strategy that would encompass all individuals affected by the disease is particularly difficult to envision. However, single strategies that would be applicable to all subjects affected by CF have been conceived and are being investigated. With all of these approaches, efficiency (the proportion of cells edited), accuracy (how often other sites in the genome are affected), and delivery of the gene editing components to the desired cells are perhaps the most significant, impending hurdles. Our understanding of each of these areas is increasing rapidly, and while it is impossible to predict when a successful strategy will reach the clinic, there is every reason to believe it is a question of "when" and not "if."

PMID: 28960896 [PubMed - as supplied by publisher]

Prenatal Bowel Findings in Male Siblings With a Confirmed FOXP3 Mutation.

J Ultrasound Med. 2017 Sep 29;:

Authors: Griswold C, Durica AR, Dennis LG, Jewell AF

Abstract
There are multiple etiologies for fetal dilated bowel loops on ultrasonography (US), and we present a unique case of male siblings with a forkhead box P3 (FOXP3) mutation. Both children presented with fetal bowel anomalies on prenatal US. Family histories of cystic fibrosis and immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome were reported. Amniocentesis in both pregnancies identified a normal male karyotype and the familial mutation associated with IPEX syndrome. IPEX syndrome is one of a group of conditions known as congenital diarrhea disorders. Other congenital diarrhea disorder cases have presented with similar prenatal US findings. As a result of these associations, we suggest considering IPEX syndrome as a potential cause of fetal bowel anomalies, particularly with a known family history. However, continued research into the phenotypic and genotypic correlations for IPEX syndrome is likely needed to better understand this possible prenatal presentation.

PMID: 28960390 [PubMed - as supplied by publisher]

Case report of a potential association between Burkholderia cepacia and preterm delivery of a twin pregnancy following in vitro fertilization.

Int J Gynaecol Obstet. 2017 Sep 28;:

Authors: Baka S, Dramountani M, Karachalios C, Michaliadis I, Kouskouni E, Panoulis K

Abstract
Vaginal colonization of Burkholderia cepacia was identified as a potentially complicating factor during a high-risk pregnancy. Although first described as a phytopathogen and used as a bio-pesticide, Burkholderia cepacia, an aerobic, glucose non-fermenting, multidrug-resistant Gram-negative rod, has emerged as a significant opportunistic pathogen causing severe pulmonary infections, mostly in patients who have cystic fibrosis and are immunocompromised [1]. Owing to its ability to survive and proliferate in nutrient-poor liquids and moist environments, hospital outbreaks have been associated with contaminated intravenous solutions, disinfectants, hospital equipment, and person-to-person contact [1,2]. This micro-organism has been isolated in vaginal cultures after using disinfectant solutions contaminated with B. cepacia for vaginal examination [2]. More importantly, even in the absence of predisposing factors, it has been recognized as a significant cause of neonatal sepsis [3]. This article is protected by copyright. All rights reserved.

PMID: 28960292 [PubMed - as supplied by publisher]

ζ potential changing nanoparticles as cystic fibrosis transmembrane conductance regulator gene delivery system: an in vitro evaluation.

Nanomedicine (Lond). 2017 Sep 29;:

Authors: Prüfert F, Bonengel S, Köllner S, Griesser J, Wilcox MD, Chater PI, Pearson JP, Bernkop-Schnürch A

Abstract
AIM: Aim of the study was the development of ζ potential changing nanoparticles as gene delivery system for the cystic fibrosis transmembrane conductance regulator gene.
METHODS: Chitosan and carboxymethyl cellulose were modified with phosphotyrosine, a substrate for the brush border enzyme alkaline phosphatase. With these synthesized derivatives, different nanoparticle formulations, including the cystic fibrosis transmembrane conductance regulator gene were prepared by ionic gelation.
RESULTS: A change from negative to positive ζ potential after enzymatic cleavage could be observed. Transfection studies with HEK-293 and Caco-2 cells showed transfection rates comparable to Lipofectamine 2000. Transfection efficiencies were significantly decreased when phosphate cleavage and thus ζ potential change was inhibited by phosphatase inhibitor.
CONCLUSION: The developed nanoparticles represent a promising gene delivery system.

PMID: 28960133 [PubMed - as supplied by publisher]

Improving the care of patients with cystic fibrosis (CF).

BMJ Open Qual. 2017;6(2):e000020

Authors: Khan AA, Nash EF, Whitehouse J, Rashid R

Abstract
BACKGROUND: The West Midlands Adult Cystic Fibrosis (CF) Centre based at Birmingham Heartlands Hospital provides care for adults with CF in the West Midlands. People with CF are prone to pulmonary exacerbations, which often require inpatient admission for intravenous antibiotics. We observed that the admission process was efficient during working hours (9:00-17:00, Monday-Friday) when the CF team are routinely available, but out-of-working hours, there were delays in these patients being clerked and receiving their first antibiotic dose. We were concerned that this was resulting in quality and potential safety issues by causing delays in starting treatment and prolonging hospital inpatient stays. We therefore undertook a quality improvement project (QIP) aimed at addressing these issues. An initial survey showed median time to clerk of 5 hours, with 60% of patients missing their first dose of antibiotics and mean length of stay of 16 days.
METHODS: We applied the Plan-Do-Study-Act (PDSA) cycle approach, with the first PDSA cycle involving raising awareness of the issue through education to doctors, nurses and patients.
RESULTS: This led to a reduction of median time to clerk from 5 to 2 hours with 23% of patients missing their first antibiotic dose and mean length of stay reducing to 14 days. The second cycle involved introducing an admissions checklist and displaying education posters around the hospital, resulting in median time to clerk remaining at 2 hours but only 20% of patients missing their first antibiotic dose and the mean length of stay remaining at 14 days.
CONCLUSION: This QIP has improved the out-of-hours admissions process for adults with CF in our centre. We plan to review the longer term effects of the project including sustainability, effects on clinical outcomes and patient satisfaction.

PMID: 28959778 [PubMed]