Predictors of sleep hypoxemia in children with cystic fibrosis.

Pediatr Pulmonol. 2019 Jan 04;:

Authors: Isaiah A, Daher A, Sharma PB, Naqvi K, Mitchell RB

Abstract
OBJECTIVES: To identify the determinants of nocturnal hypoxemia in children with CF using clinical parameters, polysomnography (PSG), and lung function.
HYPOTHESIS: Sleep hypoxemia in children with CF is predicted by both apnea hypopnea index (AHI) and percent predicted forced expiratory volume in one second (pFEV1).
DESIGN: Retrospective case series.
METHODS: Children aged 5-18 years were included based on (i) a diagnosis of CF; and (ii) availability of concurrent PSG and pFEV1 data. The impact of (i) demographic and clinical parameters; and (ii) PSG and pFEV1, on the total sleep time spent with arterial oxygen saturation below 90% (TSpO2  < 90) was measured using regression analysis. P-value <0.05 was considered significant.
RESULTS: The mean age was 11.6 years (95% confidence interval: 9.5, 13.1). Twenty of 35 (57%) were boys and the mean body mass index percentile was 42.1 (31.5, 52.6). The most common ethnicity was white (66%). OSA was diagnosed in 50%. Neither demographic predictors nor clinical variables predicted the severity of hypoxemia (R2  = 0.23, P = 0.09). While pFEV1 and PSG variables accounted for significant proportion of the overall variance in TSpO2  < 90 (R2  = 0.53, P < 0.001), pFEV1 was identified as the single best predictor of sleep hypoxemia. A pFEV1 cut-off of 53% indicated a sensitivity of 0.80 and a specificity of 0.87 in predicting sleep hypoxemia.
CONCLUSIONS: pFEV1 is the best predictor of sleep hypoxemia in children with CF and referred for PSG. No demographic or clinical predictors of hypoxemia were identified in this population.

PMID: 30609295 [PubMed - as supplied by publisher]

Comparison of two sweat test systems for the diagnosis of cystic fibrosis in newborns.

Pediatr Pulmonol. 2019 Jan 04;:

Authors: Rueegg CS, Kuehni CE, Gallati S, Jurca M, Jung A, Casaulta C, Barben J, Swiss Cystic Fibrosis Screening Group

Abstract
OBJECTIVES: In the national newborn screening programme for CF in Switzerland, we compared the performance of two sweat test methods, by investigating the feasibility and diagnostic performance of the Macroduct® collection method (with chloride mesurement) and Nanoduct® test (measuring conductivity) for diagnosing CF.
STUDY-DESIGN: We included all newborns with a positive screening result between 2011 and 2015 who were referred to a CF-centre for sweat testing. In the CF-centre, a Macroduct and Nanoduct sweat test were performed simultaneously. If sweat test results were positive or borderline, a DNA analysis was performed. Final diagnosis was based on genetic mutations.
RESULTS: Over 5 years, 445 children were screened positive and in 413 (114 with CF) at least one sweat test was performed (median age at first test, 22 days); both tests were performed in 371 children. A sweat test result was more often available with the Nanoduct compared to the Macroduct (79 vs 60%, P < 0.001). The Nanoduct was equally sensitive as the Macroduct in identifying newborns with CF (sensitivity 98 vs 99%) but less specific (specificity 79 vs 93%; P-value comparing ROC curves = 0.033).
CONCLUSIONS: This national multicentre study revealed high failure rates for Macroduct and Nanoduct in newborns in real life practice. While this needs to be addressed, our results suggested that performing the Nanoduct in addition to the Macroduct might speed up the diagnostic process because it more often yields valid results with comparable diagnostic performance. The addition of the Nanoduct sweat test can therefore help to reduce the stressful time of uncertainty for parents and to start appropriate treatment earlier.

PMID: 30609259 [PubMed - as supplied by publisher]

Lipid Peroxidation Drives Renal Cyst Growth In Vitro through Activation of TMEM16A.

J Am Soc Nephrol. 2019 Jan 03;:

Authors: Schreiber R, Buchholz B, Kraus A, Schley G, Scholz J, Ousingsawat J, Kunzelmann K

Abstract
BACKGROUND: Transepithelial chloride- secretion, through the chloride channels cystic fibrosis transmembrane conductance regulator (CFTR) and TMEM16A (anoctamin 1), drives cyst enlargement in polycystic kidney disease (PKD). Polycystic kidneys are hypoxic, and oxidative stress activates TMEM16A. However, mechanisms for channel activation in PKD remain obscure.
METHODS: Using tissue samples from patients with autosomal dominant PKD, embryonic kidney cultures, and an MDCK in vitro cyst model, we assessed peroxidation of plasma membrane phospholipids in human and mouse polycystic kidneys. We also used electrophysiologic Ussing chamber and patch clamp experiments to analyze activation of TMEM16A and growth of renal cysts.
RESULTS: Peroxidation of phospholipids in human and mouse kidneys as well as MDCK cysts in vitro is probably due to enhanced levels of reactive oxygen species. Lipid peroxidation correlated with increased cyst volume as shown in renal cultures and MDCK cysts in three-dimensional cultures. Reactive oxygen species and lipid peroxidation strongly activated TMEM16A, leading to depletion of calcium ion stores and store-operated calcium influx. Activation of TMEM16A- and CFTR-dependent chloride secretion strongly augmented cyst growth. Exposure to scavengers of reactive oxygen species, such as glutathione, coenzyme Q10, or idebenone (a synthetic coenzyme Q10 homolog), as well as inhibition of oxidative lipid damage by ferrostatin-1 largely reduced activation of TMEM16A. Inhibition of TMEM16A reduced proliferation and fluid secretion in vitro.
CONCLUSIONS: These findings indicate that activation of TMEM16A by lipid peroxidation drives growth of renal cysts. We propose direct inhibition of TMEM16A or inhibition of lipid peroxidation as potentially powerful therapeutic approaches to delay cyst development in PKD.

PMID: 30606785 [PubMed - as supplied by publisher]

Cystic fibrosis: What's new in South Africa in 2019.

S Afr Med J. 2018 Dec 13;109(1):16-19

Authors: Zampoli On Behalf Of The Msac M

Abstract
Cystic fibrosis (CF) is one of the most common autosomal recessive disorders worldwide. The incidence of CF depends on the prevalence of CFTR (cystic fibrosis transmembrane conductance regulator) gene mutations in the population, which is determined by genetic diversity and ethnicity. Over 2 000 CFTR mutation variants, divided into six distinct functional classes, are now identified, but not all cause CF disease. Advancements in the molecular diagnosis of CF and recognition of a wider spectrum of CF severity have led to recent revision of CF diagnostic nomenclature and criteria. Identifying which CFTR mutations people with CF carry is important, as novel treatments that target the specific CFTR dysfunction at a molecular level are now available, and many new drugs are in the pipeline. These and other advancements in CF are comprehensively covered in the revised 5th edition of the South African Cystic Fibrosis Consensus Guidelines, published in 2017. In addition, the South African Cystic Fibrosis Registry Initiative (SACFRI) was launched in April 2018. SACFRI is a multicentre public-private collaboration of CF healthcare providers across South Africa (SA), which will prospectively collect data relating to CF diagnosis and outcomes in SA. Local SA registry data are critical to understanding the epidemiology of CF in SA, and SACFRI will be an important tool to identify and prioritise areas of CF care that require intervention.

PMID: 30606298 [PubMed - in process]

Quantifying microbial chatter: scanning electrochemical microscopy as a tool to study interactions in biofilms.

Proc Math Phys Eng Sci. 2018 Dec;474(2220):20180405

Authors: Darch SE, Koley D

Abstract
Bacteria are often found in their natural habitats as spatially organized biofilm communities. While it is clear from recent work that the ability to organize into precise spatial structures is important for fitness of microbial communities, a significant gap exists in our understanding regarding the mechanisms bacteria use to adopt such physical distributions. Bacteria are highly social organisms that interact, and it is these interactions that have been proposed to be critical for establishing spatially structured communities. A primary means by which bacteria interact is via small, diffusible molecules including dedicated signals and metabolic by-products; however, quantitatively monitoring the production of these molecules in time and space with the micron-scale resolution required has been challenging. In this perspective, scanning electrochemical microscopy (SECM) is discussed as a powerful tool to study microbe-microbe interactions through the detection of small redox-active molecules. We highlight SECM as a means to quantify and spatially resolve the chemical mediators of bacterial interactions and begin to elucidate the mechanisms used by bacteria to regulate the emergent properties of biofilms.

PMID: 30602930 [PubMed]

Peripheral blood immunophenotyping in a large cohort of patients with Shwachman-Diamond syndrome.

Pediatr Blood Cancer. 2019 Jan 02;:e27597

Authors: Bezzerri V, Vella A, Gennaro GD, Ortolani R, Nicolis E, Cesaro S, Fabrizzi B, Bronte V, Corey SJ, Cipolli M

Abstract
Shwachman-Diamond syndrome (SDS) is one of the more common inherited bone marrow failure syndromes, characterized by neutropenia, occasional thrombocytopenia, and anemia. Bone marrow evaluation reveals an increased number of monocytes and mature B cells along with decreased granulocytes. However, little is known about the subpopulations of peripheral blood cells, and few previous publications have been based on a small number of patients. Here, we report a comprehensive immunophenotypic analysis from a cohort of 37 SDS patients who display impairment mostly in the myeloid compartment with a deficiency also in the number of B cells and CD4/CD8 double-negative T cells.

PMID: 30604473 [PubMed - as supplied by publisher]

Cystic fibrosis in Tunisian children: a review of 32 children.

Afr Health Sci. 2018 Sep;18(3):664-670

Authors: Boussetta K, Khalsi F, Bahri Y, Belhadj I, Tinsa F, Messaoud TB, Hamouda S

Abstract
Background: Cystic fibrosis is rare in Tunisia. Its diagnosis requires experienced specialists. Its prognosis is poor in developing countries.
Objectives: To study the epidemiologic, clinical, genetic features and the therapeutic challenges of cystic fibrosis in Tunisian children.
Methods: Covering a period of 21 years, this retrospective study included all patients with a definite diagnosis of cystic fibrosis from the Pediatrics Department B of The Children's Hospital of Tunis.
Results: Data from 32 children (14 boys and 18 girls) were collected. The diagnosis was made during the first year of life in 28 cases. Meconium ileus was found in 5 cases, respiratory manifestations in 22 cases, chronic diarrhea in 19 cases, faltering growth in 17 cases and a pseudo Barter syndrome in 2 cases. The sweat chloride test was positive in all cases. The most frequent mutation was F508del (56% of cases). Respiratory complications marked the outcome. Among our 32 patients, 15 patients (50%) died at an average age of 5 years and 3 months, mainly due to respiratory failure. The mean age of the surviving patients was 5 years.
Conclusion: Cystic fibrosis prognosis is poor in our series compared to developed countries due to the longer diagnostic delay and the limited therapeutic options.

PMID: 30602999 [PubMed - in process]

The Role of Genetics in Pancreatitis.

Gastrointest Endosc Clin N Am. 2018 Oct;28(4):587-603

Authors: Hasan A, Moscoso DI, Kastrinos F

Abstract
Individuals with acute recurrent and chronic pancreatitis may have an inherited predisposition to the development of the disease. Pancreatitis in the setting of a significant family history of the disease can be classified as hereditary or familial pancreatitis. In this article, the authors closely examine the specific genes implicated in pancreatitis, investigate the role of genetic testing for diagnosis, and describe the impact of genetic testing results on clinical management.

PMID: 30241646 [PubMed - indexed for MEDLINE]

Improving the Affordability of Prescription Medications for People with Chronic Respiratory Disease. An Official American Thoracic Society Policy Statement.

Am J Respir Crit Care Med. 2018 Dec 01;198(11):1367-1374

Authors: Patel MR, Press VG, Gerald LB, Barnes T, Blake K, Brown LK, Costello RW, Crim C, Forshag M, Gershon AS, Goss CH, Han MK, Lee TA, Sweet S, Gerald JK

Abstract
BACKGROUND: Mounting evidence indicates that out-of-pocket costs for prescription medications, particularly among low- and middle-income patients with chronic diseases, are imposing financial burden, reducing medication adherence, and worsening health outcomes. This problem is exacerbated by a paucity of generic alternatives for prevalent lung diseases, such as asthma and chronic obstructive pulmonary disease, as well as high-cost medicines for rare diseases, such as cystic fibrosis. Affordability and access challenges are especially salient in the United States, as citizens of many other countries pay lower prices for and have greater access to prescription medications.
METHODS: The American Thoracic Society convened a multidisciplinary committee comprising experts in health policy pharmacoeconomics, behavioral sciences, and clinical care, along with individuals providing industry and patient perspectives. The report and its recommendation were iteratively developed over a year of in-person, telephonic, and electronic deliberation.
RESULTS: The committee unanimously recommended the establishment of a publicly funded, politically independent, impartial entity to systematically draft evidence-based pharmaceutical policy recommendations. The goal of this entity would be to generate evidence and action steps to ensure people have equitable and affordable access to prescription medications, to maximize the value of public and private pharmaceutical expenditures on health, to support novel drug development within a market-based economy, and to preserve clinician and patient choice regarding personalized treatment. An immediate priority is to examine the evidence and make recommendations regarding the need to have essential medicines with established clinical benefit from each drug class in all Tier 1 formularies and propose recommendations to reduce barriers to timely generic drug availability.
CONCLUSIONS: By making explicit, evidence-based recommendations, the entity can support the establishment of coherent national policies that expand access to affordable medications, improve the health of patients with chronic disease, and optimize the use of public and private resources.

PMID: 30601674 [PubMed - in process]

Evaluation of noninvasive markers for the diagnosis of cystic fibrosis liver disease.

Scand J Gastroenterol. 2019 Jan 02;:1-6

Authors: Alexopoulou A, Pouriki S, Vasilieva L, Alexopoulos T, Filaditaki V, Gioka M, Diamantea F, Dourakis SP

Abstract
OBJECTIVES: In cystic fibrosis (CF), liver disease (LD) is the third leading cause of mortality. As liver biopsy was considered inconsistent in CFLD diagnosis, a combination of modalities were utilized in the conventional Debray criteria (DC). More recently, noninvasive liver fibrosis biomarkers were applied by Koh et al (New criteria-NC). In the current study, we aimed to evaluate noninvasive biomarkers for the CFLD diagnosis.
METHODS: Longitudinal data were collected from a cohort of genetically confirmed CF patients. CFLD was diagnosed by both DC and NC. Apart from transient elastography (TE) > 6.8 kPa, biomarkers incorporated in the NC included AST/ALT-ratio (AAR) ≥ 1, FIB-4 index ≥3.25 and APRI >0.50.
RESULTS: 62 patients with CF, [56.5% male, age at enrollment 25 (22-31) years], were prospectively followed-up for 33 (28-36) months. Sixteen (25.8%) and 27 (43.5%) patients met DC and NC, respectively. Twenty-four fulfilling NC had at least one positive biomarker (6 TE, 7 AAR, 6 both TE and AAR, 2 both APRI and AAR and 3 both APRI and TE). Thirteen (48.1%) had diffuse LD/cirrhosis by the NC and all had at least one additional parameter classifying them as CFLD. From the 14 (51.8%) with no-diffuse-LD, 64.3%, 14.3% and 21.4% had 2, 3 and 4 of the necessary modalities incorporated in NC, respectively, confirming their classification as CFLD. TE was 100% specific to rule in CFLD but had a moderate sensitivity.
CONCLUSIONS: NC were able to identify 17.7% more CFLD patients compared to DC. The multiple biomarkers incorporated in NC may enhance the ability to detect CFLD.

PMID: 30600723 [PubMed - as supplied by publisher]

Functional analysis of the p.[Arg74Trp;Val201Met;Asp1270Asn]/p.Phe508del CFTR mutation genotype in human native colon.

Mol Genet Genomic Med. 2019 Jan 01;:

Authors: Schucht S, Minso R, Lex C, Reiss J, Stanke F, Tamm S, van Barneveld A, Tümmler B

Abstract
BACKGROUND: The impact of complex alleles on CFTR processing and function has yet not been investigated in native human tissue.
METHODS: Intestinal current measurements (ICM) followed by CFTR immunoblot were performed on rectal biopsies taken from two siblings who are compound heterozygous for the CFTR mutations p.Phe508del and the complex allele p.[Arg74Trp;Val201Met;Asp1270Asn].
RESULTS: Normal and subnormal chloride secretory responses in the ICM were associated with normal and fourfold reduced amounts of the mature glycoform band C CFTR, respectively, consistent with the unequal clinical phenotype of the siblings.
CONCLUSION: The combined use of bioassay and protein analysis is particularly meaningful to resolve the CFTR phenotype of "indeterminate" borderline CFTR genotypes on a case-to-case basis.

PMID: 30600599 [PubMed - as supplied by publisher]

A posttranslational modification code for CFTR maturation is altered in cystic fibrosis.

Sci Signal. 2019 Jan 01;12(562):

Authors: Pankow S, Bamberger C, Yates JR

Abstract
The multistep process regulating the maturation of membrane proteins in the endoplasmic reticulum (ER) and the secretory pathway is disrupted in many protein misfolding disorders. Mutations in the ion channel CFTR that impair its folding and subsequent localization to the plasma membrane cause cystic fibrosis (CF), an inherited and eventually lethal disease that impairs the function of multiple organs, mostly the lungs. Here, we found that proper maturation of CFTR is dependent on cross-talk between phosphorylation and methylation events in the regulatory insertion (RI) element of the protein. Manipulating these posttranslational modifications (PTMs) prevented the maturation of wild-type CFTR and instead induced its degradation by ER quality control systems. Deletion of Phe508 (ΔF508), the most prevalent mutation in CF, and other mutations in CFTR that impair its trafficking, such as N1303K, also led to quantitative and qualitative PTM changes that prevented the maturation of misfolded CFTR. Further analysis revealed that a wild-type CFTR-like PTM pattern and function was restored in ΔF508 CFTR when cells were cultured at 28°C but only in the presence of the kinase CK2α. Furthermore, the ability to replicate this PTM pattern predicted the efficacy of treatments in restoring ΔF508 CFTR activity. Accordingly, evaluation of patient information revealed that point mutations of several of the modification sites are associated with clinical CF. These findings identify a minimal quantitative and qualitative PTM code for CFTR maturation that distinguishes correctly folded from misfolded CFTR.

PMID: 30600261 [PubMed - in process]

Bio-psycho-social-spiritual needs of adolescents and young adults with life-threatening illnesses: Implications for social work practice.

Soc Work Health Care. 2018 04;57(4):250-266

Authors: Beerbower E, Winters D, Kondrat D

Abstract
This paper explores the biopsychosocial and spiritual needs of adolescents and young adults (AYA) with life-threatening or terminal illnesses. AYA are situated between childhood and adulthood (ages 15-25) and have distinct biopsychosocial and spiritual needs unique to their developmental stage. Having a life-threatening or terminal illness directly challenges normal AYA developmental tasks and identity formation. AYA experience more troubling physical symptoms during the dying process compared to other age groups, which leads to significant psychological distress and an increased need for pharmacological treatments. In general, AYA desire to be fully informed and involved in the health care decision-making process, leading to ethical dilemmas when the AYA is a minor and their wishes differ from the wishes of their legal guardian(s). Social workers are especially well-equipped to serve this population due to aligning professional standards and ability to advocate for holistic care within interdisciplinary teams. Additional research is needed to tailor holistic interventions to meet the needs of this population.

PMID: 29377778 [PubMed - indexed for MEDLINE]

Vertex CF data wow Wall Street.

Nat Biotechnol. 2017 09 11;35(9):807

Authors:

PMID: 28898228 [PubMed - indexed for MEDLINE]

Sensorineural hearing loss in children with sickle cell disease.

Int J Pediatr Otorhinolaryngol. 2018 Dec 05;118:110-114

Authors: Farrell AN, Landry AM, Yee ME, Leu RM, Goudy SL

Abstract
INTRODUCTION: Sensorineural hearing loss (SNHL) has been reported to occur at increased frequency in the pediatric sickle cell disease (SCD) population, likely secondary to ototoxic medication regimens and repeat sickling events that lead to end organ damage. Risk and protective factors of SNHL in this population are not fully characterized. The objective of this study was to describe audiology results in children with SCD and the prevalence and sequelae of SNHL.
METHODS: A comprehensive clinical database of 2600 pediatric SCD patients treated at 1 institution from 2010-16 was retrospectively reviewed to identify all patients who were referred for audiologic testing. Audiologic test results, patient characteristics, and SCD treatments were reviewed.
RESULTS: 181 SCD children (97 male, 153 HbSS) underwent audiologic testing, with 276 total audiology encounters, ranging 1-9 per patient. Mean age at first audiogram was 8.9 ± 5.2 years. 29.8% had prior cerebrovascular infarct and an additional 25.4% had prior abnormal transcranial Doppler screens documented at time of first audiogram. Overall, 13.3% had documented hearing loss, with 6.6% SNHL. Mean pure tone average (PTA) among patients with SNHL ranged from mild to profound hearing loss (Right: 43.3 ± 28.9, Left: 40.8 ± 29.7), sloping to more severe hearing loss at higher frequencies.
CONCLUSIONS: Hearing loss was identified in a significant subset of children with SCD and the hearing loss ranged from normal to profound. Though the overall prevalence of SNHL in SCD patients was low, baseline audiology screening should be considered.

PMID: 30599285 [PubMed - as supplied by publisher]

Structural and functional characterization of TgpA, a critical protein for the viability of Pseudomonas aeruginosa.

J Struct Biol. 2018 Dec 29;:

Authors: Uruburu M, Mastrangelo E, Bolognesi M, Ferrara S, Bertoni G, Milani M

Abstract
Pseudomonas aeruginosa is an opportunistic pathogen associated with severe diseases, such as cystic fibrosis. During an extensive search for novel essential genes, we identified tgpA (locus PA2873) in P. aeruginosa PAO1, as a gene playing a critical role in bacterial viability. TgpA, the translated protein, is an internal membrane protein with a periplasmic soluble domain, predicted to be endowed with a transglutaminase-like fold, hosting the Cys404, His448, and Asp464 triad. We report here that Cys404 mutation hampers the essential role of TgpA in granting P. aeruginosa viability. Moreover, we present the crystal structure of the TgpA periplasmic domain at 1.6 Å resolution as a first step towards structure-activity analysis of a new potential target for the discovery of antibacterial compounds.

PMID: 30599211 [PubMed - as supplied by publisher]

Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion.

Cell Mol Life Sci. 2019 Jan 01;:

Authors: Valdivieso ÁG, Clauzure M, Massip-Copiz MM, Cancio CE, Asensio CJA, Mori C, Santa-Coloma TA

Abstract
Mutations in the gene encoding the CFTR chloride channel produce cystic fibrosis (CF). CF patients are more susceptible to bacterial infections in lungs. The most accepted hypothesis sustains that a reduction in the airway surface liquid (ASL) volume favor infections. Alternatively, it was postulated that a reduced HCO3- transport through CFTR leads to a decreased ASL pH, favoring bacterial colonization. The issue is controversial, since recent data from cultured primary cells and CF children showed normal pH values in the ASL. We have reported previously a decreased mitochondrial Complex I (mCx-I) activity in cultured cells with impaired CFTR activity. Thus, we hypothesized that the reduced mCx-I activity could lead to increased lactic acid production (Warburg-like effect) and reduced extracellular pH (pHe). In agreement with this idea, we report here that cells with impaired CFTR function (intestinal Caco-2/pRS26, transfected with an shRNA-CFTR, and lung IB3-1 CF cells) have a decreased pHe. These cells showed increased lactate dehydrogenase (LDH) activity, LDH-A expression, and lactate secretion. Similar effects were reproduced in control cells stimulated with recombinant IL-1β. The c-Src and JNK inhibitors PP2 and SP600125 were able to increase the pHe, although the differences between control and CFTR-impaired cells were not fully compensated. Noteworthy, the LDH inhibitor oxamate completely restored the pHe of the intestinal Caco-2/pRS26 cells and have a significant effect in lung IB3-1 cells; therefore, an increased lactic acid secretion seems to be the key factor that determine a reduced pHe in these epithelial cells.

PMID: 30599064 [PubMed - as supplied by publisher]

[Follow-up protocol of patients with cystic fibrosis diagnosed by newborn screening].

An Pediatr (Barc). 2018 Dec 28;:

Authors: Gartner S, Mondéjar-López P, Asensio de la Cruz Ó, Grupo de Trabajo de Fibrosis Quística de la Sociedad Española de Neumología Pediátrica

Abstract
Newborn screening (NBS) for cystic fibrosis (CF) is well-established in many countries and provides the opportunity for an early diagnosis and treatment before the development of irreversible structural lung damage. In 1999, Catalonia, Castilla-León, and the Balearic Islands started the NBS programme for CF. In the last 10 years its implementation rapidly spread and all the autonomies offer the NBS programme for CF since 2015. There are many different strategies across Spain. It is believed that it is very opportune to have an updated and consensual guide for the diagnosis, follow-up, and treatment of patients diagnosed by neonatal screening.

PMID: 30598406 [PubMed - as supplied by publisher]

Integrative expression analysis identifies a novel interplay between CFTR and linc-SUMF1-2 that involves CF-associated gene dysregulation.

Biochem Biophys Res Commun. 2018 Dec 28;:

Authors: Kamei S, Maruta K, Fujikawa H, Nohara H, Ueno-Shuto K, Tasaki Y, Nakashima R, Kawakami T, Eto Y, Suico MA, Suzuki S, Gruenert DC, Li JD, Kai H, Shuto T

Abstract
Cystic fibrosis transmembrane regulator (CFTR) is a cyclic AMP-dependent Cl- channel, and its dysfunction, due to CFTR gene mutations, causes the lethal inherited disorder cystic fibrosis (CF). To date, widespread dysregulation of certain coding genes in CF airway epithelial cells is well studied and considered as the driver of pulmonary abnormality. However, the involvement of non-coding genes, novel classes of functional RNAs with little or no protein-coding capacity, in the regulation of CF-associated gene dysregulation is poorly understood. Here, we utilized integrative analyses of human transcriptome array (HTA) and characterized 99 coding and 91 non-coding RNAs that are dysregulated in CFTR-defective CF bronchial epithelial cell line CFBE41o-. Among these genes, the expression level of linc-SUMF1-2, an intergenic non-coding RNA (lincRNA) whose function is unknown, was inversely correlated with that of WT-CFTR and consistently higher in primary human CF airway epithelial cells (DHBE-CF). Further integrative analyses under linc-SUMF1-knockdown condition determined MXRA5, SEMA5A, CXCL10, AK022877, CTGF, MYC, AREG and LAMB3 as both CFTR- and linc-SUMF1-2-dependent dysregulated gene sets in CF airway epithelial cells. Overall, our analyses reveal linc-SUMF1-2 as a dysregulated non-coding gene in CF as well as CFTR-linc-SUMF1-2 axis as a novel regulatory pathway involved in CF-associated gene dysregulation.

PMID: 30598261 [PubMed - as supplied by publisher]

Successful lung transplantation for chronic Mycobacterium abscessus infection in advanced cystic fibrosis, a case series.

Transpl Infect Dis. 2018 Dec 30;:e13046

Authors: Raats D, Lorent N, Saegeman V, Vos R, Van Ingen J, Verleden G, Van Raemdonck D, Dupont L

Abstract
Pulmonary Mycobacterium abscessus infection in cystic fibrosis (CF) patients is difficult to treat and considered a contra-indication for lung transplantation in most centers. We present four CF patients with chronic pulmonary M. abscessus infection, in whom lung transplantation was performed. Through intensive treatment before transplantation, we achieved control of the infection in all but one patient. After a mean of 16 months of follow up, three patients are doing well, without evidence of local or disseminated recurrence. One patient died early post-transplant due to an unrelated cause. These findings support the possibility of lung transplantation with favorable outcome in CF patients with M. abscessus infection. This article is protected by copyright. All rights reserved.

PMID: 30597699 [PubMed - as supplied by publisher]