Bronchoscopic instillation of DNase to manage refractory lobar atelectasis in a lung cancer patient.

Ann Transl Med. 2019 Aug;7(15):363

Authors: Assallum H, Song TY, DeLorenzo L, Harris K

Abstract
Lobar atelectasis is a common complication in lung cancer. It can be caused by direct endobronchial tumorous seeding or indirectly by mucus plugs due to bacterial lung infections. Treatment is usually conservative, with or without therapeutic bronchoscopy. Dornase alfa is a recombinant human deoxyribonuclease I (rhDNase), an enzyme that selectively cleaves DNA, thus reducing mucous viscosity. rhDNase has been used as a mucolytic agent in cystic fibrosis (CF) patients. Though bronchoscopically instilled rhDNase has been reported as a treatment for persistent lobar atelectasis in newborn and pediatric populations, its use in adults has not been well established.

PMID: 31516909 [PubMed]

Mycophenolate mofetil as an alternative treatment in sarcoidosis.

Pulm Pharmacol Ther. 2019 Sep 10;:101840

Authors: Papiris S, Stagaki E, Papadaki G, Kolilekas L, Korbila I, Apollonatou V, Kallieri M, Gialafos H, Chatziioannou S, Papaioannou AI, Manali ED

Abstract
INTRODUCTION: In sarcoidosis although no better drug therapy than corticosteroids (CS) has emerged, alternative immunosuppressive agents are used when indicated. Mycophenolate mofetil (MMF) presents rapid action, a considerable safety profile and absence of lung toxicity. Few data exist so far on its use in patients with sarcoidosis. This is a retrospective study on the effectiveness and safety of MMF in patients with sarcoidosis.
MATERIALS AND METHODS: All patients with biopsy proven sarcoidosis treated for at least 1 year with MMF from 2008 to 2017 in our department are evaluated.
RESULTS: Eight patients with both pulmonary and extrapulmonary disease are included in the analysis. During follow-up, symptoms and chest radiological findings improved in all. A statistically significant improvement of FEV1 and FVC is reported (p = 0.010 and p = 0.021 respectively). Cardiac and renal disease resolved during treatment while dermal disease significantly improved. MMF permitted CS dose reduction from 15.0 (10.0, 35.0) to 2.5 (0.0, 5.0) mg prednisolone (or equivalent), p = 0.016. All patients but one, tolerated well MMF.
CONCLUSION: MMF as an alternative drug in systemic sarcoidosis, proved safe and effective, permitting the reduction of the dose of oral CS and leading to clinical, functional and radiological improvement.

PMID: 31518648 [PubMed - as supplied by publisher]

The COPD multi-dimensional phenotype: A new classification from the STORICO Italian observational study.

PLoS One. 2019;14(9):e0221889

Authors: Antonelli Incalzi R, Canonica GW, Scichilone N, Rizzoli S, Simoni L, Blasi F, STORICO study group

Abstract
BACKGROUND: This paper is aimed to (i) develop an innovative classification of COPD, multi-dimensional phenotype, based on a multidimensional assessment; (ii) describe the identified multi-dimensional phenotypes.
METHODS: An exploratory factor analysis to identify the main classificatory variables and, then, a cluster analysis based on these variables were run to classify the COPD-diagnosed 514 patients enrolled in the STORICO (trial registration number: NCT03105999) study into multi-dimensional phenotypes.
RESULTS: The circadian rhythm of symptoms and health-related quality of life, but neither comorbidity nor respiratory function, qualified as primary classificatory variables. Five multidimensional phenotypes were identified: the MILD COPD characterized by no night-time symptoms and the best health status in terms of quality of life, quality of sleep, level of depression and anxiety, the MILD EMPHYSEMATOUS with prevalent dyspnea in the early-morning and day-time, the SEVERE BRONCHITIC with nocturnal and diurnal cough and phlegm, the SEVERE EMPHYSEMATOUS with nocturnal and diurnal dyspnea and the SEVERE MIXED COPD distinguished by higher frequency of symptoms during 24h and worst quality of life, of sleep and highest levels of depression and anxiety.
CONCLUSIONS: Our results showed that properly collected respiratory symptoms play a primary classificatory role of COPD patients. The longitudinal observation will disclose the discriminative and prognostic potential of the proposed multidimensional phenotype.
TRIAL REGISTRATION: Trial registration number: NCT03105999, date of registration: 10th April 2017.

PMID: 31518364 [PubMed - in process]

Validation of the "Good2Go": the first French-language transition readiness questionnaire.

Eur J Pediatr. 2019 Sep 13;:

Authors: Mellerio H, Jacquin P, Trelles N, Le Roux E, Belanger R, Alberti C, Tubiana-Rufi N, Stheneur C, Guilmin-Crépon S, Devilliers H

Abstract
The use of transition readiness questionnaires is strongly recommended in adolescents with chronic conditions. The aim of our study was to validate "Good2Go," the first French-language transition readiness questionnaire. We analyzed the data from 2 multicentric studies (Canada and France) involving adolescents with chronic conditions (type 1 diabetes, inflammatory bowel disease, cystic fibrosis, epilepsy, juvenile idiopathic arthritis). Content and construct validity were examined using factorial and Rasch analysis (structural validity), Spearman's correlation, and Mann-Whitney test (external validity). Cronbach's α and intra-class correlation coefficients explored reliability. Cognitive interviews assessed wording comprehension and item appropriateness. Good2Go was completed by 321 participants (boys = 51%; mean age = 16.4 years (standard deviation = 1.5; min = 14.0; max = 18.0); Canada = 51.1%). Factor analysis identified 3 domains: "health self-advocacy," "knowledge about chronic conditions," and "self-management skills." The 3-domain structure showed a satisfying Rasch fit, internal consistency, and test-retest reliability. Good2Go domain scores were significantly higher in participants over 17 years of age, indicating satisfactory external validity.Conclusion: Good2Go is a valid 20-item questionnaire to assess transition readiness in adolescents with chronic conditions and may be useful in routine care to propose individually tailored preparation for their transfer to adult healthcare. Further research is now needed to analyze correlation between domain scores and success of transition. What is Known: • In adolescents with chronic conditions, the use of transition readiness questionnaires is recommended to propose individually tailored preparation for their transfer to adult healthcare. • However, no French-language questionnaire has been so far validated. What is New: • Based on a complete validation methodology, this study highlights that the French-language 20-items Good2Go questionnaire has good psychometric properties. • It explores all transition key points though 3 scored domains: "health self-advocacy", "knowledge about chronic disease" and "self-management skills".

PMID: 31515671 [PubMed - as supplied by publisher]

An Unusual Lung Mass of Heterotopic Pancreatic Tissue in a Neonate With an Elevated Immunoreactive Trypsinogen on Newborn Screen.

Pediatr Dev Pathol. 2019 Sep 12;:1093526619876820

Authors: Rao A, Wagner ES, Wieck MM, Raiji MT, Schulte JJ, Husain AN, Azzam R

Abstract
We present a case of a neonate with tracheoesophageal fistula and esophageal atresia along with a suspicious lung mass who had a false-positive newborn screen for cystic fibrosis due to an elevated serum immunoreactive trypsinogen with an additionally elevated serum lipase. The infant's lung mass was found to contain heterotopic pancreatic tissue consisting of acini, ducts, and islet cells, without an associated gastrointestinal duplication cyst. This constellation of congenital abnormalities has not been described in previous literature. Also, this is the first reported case of a neonate with elevated serum pancreatic enzymes in which the underlying etiology was discovered to be heterotopic pancreas.

PMID: 31514577 [PubMed - as supplied by publisher]

Niche partitioning of a pathogenic microbiome driven by chemical gradients.

Sci Adv. 2018 09;4(9):eaau1908

Authors: Quinn RA, Comstock W, Zhang T, Morton JT, da Silva R, Tran A, Aksenov A, Nothias LF, Wangpraseurt D, Melnik AV, Ackermann G, Conrad D, Klapper I, Knight R, Dorrestein PC

Abstract
Environmental microbial communities are stratified by chemical gradients that shape the structure and function of these systems. Similar chemical gradients exist in the human body, but how they influence these microbial systems is more poorly understood. Understanding these effects can be particularly important for dysbiotic shifts in microbiome structure that are often associated with disease. We show that pH and oxygen strongly partition the microbial community from a diseased human lung into two mutually exclusive communities of pathogens and anaerobes. Antimicrobial treatment disrupted this chemical partitioning, causing complex death, survival, and resistance outcomes that were highly dependent on the individual microorganism and on community stratification. These effects were mathematically modeled, enabling a predictive understanding of this complex polymicrobial system. Harnessing the power of these chemical gradients could be a drug-free method of shaping microbial communities in the human body from undesirable dysbiotic states.

PMID: 30263961 [PubMed - indexed for MEDLINE]

ICER report for peanut OIT comes up short.

Ann Allergy Asthma Immunol. 2019 Sep 09;:

Authors: Eiwegger T, Anagnostou K, Arasi S, Bégin P, Ben-Shoshan M, Beyer K, Blumchen K, Brough H, Caubet JC, Chan ES, Chinthrajah S, Davis CM, Roches AD, Du Toit G, Elizur A, Galli SJ, Håland G, Hoffmann-Sommergruber K, Kim H, Leung DYM, Muraro A, Nurmatov UB, Pajno GB, Sindher S, Szepfalusi Z, Torres MJ, Upton J, Worm M, Nadeau K

PMID: 31513908 [PubMed - as supplied by publisher]

Synchronous multiple non-small cell lung cancers in an allograft lung recipient.

Lung Cancer. 2018 10;124:291-292

Authors: Pujol JL, Jean-Baptiste S, Bommart S, Roch B

Abstract
We described a case report of synchronous non-small cell lung cancers arising in lung transplants after allograft. Immunosuppressive therapy of the recipient induced an accelerated growth rate of primary tumour and metastases as was been observed in orthotopic liver allograft for hepatocellular carcinoma.

PMID: 30268475 [PubMed - indexed for MEDLINE]

Prevalence of Bactericidal/Permeability-Increasing Protein Autoantibodies in Cystic Fibrosis Patients: Systematic Review and Meta-Analysis.

Pediatr Allergy Immunol Pulmonol. 2019 Jun 01;32(2):45-51

Authors: Iwuji K, Larumbe-Zabala E, Bijlani S, Nugent K, Kanu A, Manning E, Solis X

Abstract
Background: There have been varying reports on the prevalence of antineutrophil cytoplasmic antibodies with bactericidal/permeability-increasing protein (BPI-ANCA) specificity in cystic fibrosis (CF) patients. These autoantibodies are believed to develop in response to infection and colonization, especially with Pseudomonas aeruginosa. The aim of this review was to estimate the overall prevalence of BPI-ANCA in CF patients. Methods: We searched PubMed, Scopus, and Embase databases for studies reporting the prevalence of BPI-ANCA in CF patients. We also searched the Journal of Cystic Fibrosis and our institution's library for relevant studies on BPI-ANCA. We calculated the proportion with a 95% confidence interval (CI) to assess the prevalence of BPI-ANCA in the individual studies and then pooled the results using a random effects model. Publication bias was assessed using graphical and statistical methods. Finally, we assessed statistical heterogeneity using the I 2 test. Results: Our search yielded 12 eligible studies published between 1996 and 2015. The prevalence of BPI-ANCA in patients with CF varied from 17.9% to 83% with a pooled prevalence of 49.45% (95% CI 35.53-63.42). No evidence of bias was found. However, there was evidence of statistically significant variation in the prevalence estimate due to heterogeneity (I 2 = 93.4%, P < 0.01). Conclusions: Given the highly varying prevalence of BPI-ANCA in patients with CF, more well-designed prospective clinical studies are needed to determine its true prevalence and clinical relevance.

PMID: 31508255 [PubMed]

Predictive value of genomic screening: cross-sectional study of cystic fibrosis in 50,788 electronic health records.

NPJ Genom Med. 2019;4:21

Authors: Sugunaraj JP, Brosius HM, Murray MF, Manickam K, Stamm JA, Carey DJ, Mirshahi UL

Abstract
Doubts have been raised about the value of DNA-based screening for low-prevalence monogenic conditions following reports of testing this approach using available electronic health record (EHR) as the sole phenotyping source. We hypothesized that a better model for EHR-focused examination of DNA-based screening is Cystic Fibrosis (CF) since the diagnosis is proactively sought within the healthcare system. We reviewed CFTR variants in 50,778 exomes. In 24 cases with bi-allelic pathogenic CFTR variants, there were 21 true-positives. We considered three cases "potential" false-positives due to limitations in available EHR phenotype data. This genomic screening exhibited a positive predictive value of 87.5%, negative predictive value of 99.9%, sensitivity of 95.5%, and a specificity of 99.9%. Despite EHR-based phenotyping limitations in three cases, the presence or absence of pathogenic CFTR variants has strong predictive value for CF diagnosis when EHR data is used as the sole phenotyping source. Accurate ascertainment of the predictive value of DNA-based screening requires condition-specific phenotyping beyond available EHR data.

PMID: 31508243 [PubMed]

Rethinking Strategies for Positive Newborn Screening Result (NBS+) Delivery (ReSPoND): a process evaluation of co-designing interventions to minimise impact on parental emotional well-being and stress.

Pilot Feasibility Stud. 2019;5:108

Authors: Chudleigh J, Bonham J, Bryon M, Francis J, Moody L, Morris S, Simpson A, Ulph F, Southern K

Abstract
Background: Newborn blood spot (NBS) screening seeks to prevent ill health, disability and death through early diagnosis and effective intervention. Each year, around 10,000 parents of babies born in England are given a positive NBS result indicating their child may be affected or carriers of one of the nine conditions currently screened for. Despite guidance, these results are inconsistently delivered to parents across geographical regions. There is evidence that many parents are dissatisfied with how NBS results are communicated to them and that poor communication practices can lead to various negative sequelae. The purpose of this study is to co-design, implement and undertake a process evaluation of new, co-designed interventions to improve delivery of initial positive NBS results to parents.
Methods: This mixed-methods study will use four phases with defined outputs. Family Systems Theory will form the theoretical basis for the study. The principles and methods of experience-based co-design will underpin intervention development. Normalisation Process Theory will underpin the process evaluation of the interventions co-designed to improve the delivery of positive NBS results to parents. An economic analysis will determine resource use and costs of current practice and of implementing the new co-designed interventions. The nominal group technique will be used to inform the selection of suitable outcome measures for a future evaluation study.
Discussion: The main output of the proposed study will be co-designed interventions for initial communication of positive NBS results to parents ready to be evaluated in a definitive evaluation study.The interventions, co-designed with parents, will help to minimise potential negative sequelae associated with poor communication practices by considering parental and staff experiences as well as healthcare challenges such as finite resources. In addition, information about indicative costs associated with different communication strategies will be determined.It is anticipated it may also be possible to extrapolate principles of good communication practices from the present study for the delivery of bad news to parents for children newly diagnosed with other conditions including cancer and other chronic conditions such as diabetes or epilepsy.
Trial registration: ISRCTN 15330120 date of registration 17/01/2018.

PMID: 31508239 [PubMed]

Diagnostic imaging in adult 
non-cystic fibrosis bronchiectasis.

Breathe (Sheff). 2019 Sep;15(3):190-197

Authors: Juliusson G, Gudmundsson G

Abstract
Radiology plays a key role in the diagnosis of bronchiectasis, defined as permanent dilatation of the bronchial lumen. Volumetric thin-section multidetector computed tomography is an excellent noninvasive modality to evaluate bronchiectasis. Bronchiectasis is categorised by morphological appearance. Cylindrical bronchiectasis has a smooth tubular configuration and is the most common form. Varicose bronchiectasis has irregular contours with alternating dilating and contracting lumen. Cystic bronchiectasis is the most severe form and exhibits saccular dilatation of bronchi. Bronchial dilatation is the hallmark of bronchiectasis and is evaluated in relation to the accompanying pulmonary artery. A broncho-arterial ratio exceeding 1:1 should be considered abnormal. Normal bronchi are narrower in diameter the further they are from the lung hila. Lack of normal bronchial tapering over 2 cm in length, distal from an airway bifurcation, is the most sensitive sign of bronchiectasis. Findings commonly associated with bronchiectasis include bronchial wall thickening, mucus plugging and tree-in-bud opacities. Bronchiectasis results from a myriad of conditions, with post-infectious bronchiectasis being the most common. Imaging can sometimes discern the cause of bronchiectasis. However, in most cases it is nonspecific or only suggestive of aetiology. While morphological types are nonspecific, the distribution of abnormality offers clues to aetiology.
Key points: Bronchiectasis is a chronic progressive condition with significant disease burden and frequent exacerbations, for which the diagnosis relies on cross-sectional imaging.The major imaging findings include bronchial dilatation, bronchial contour abnormalities and visualisation of the normally invisible peripheral airways.Bronchiectasis is the end result of various conditions, including immunodeficiencies, mucociliary disorders and infections. Imaging is often nonspecific with regard to aetiology but can be suggestive.Distribution of abnormality in the lung offers helpful clues for establishing aetiology.
Educational aims: To review the cross-sectional imaging appearance of bronchiectasis and the common associated findings.To get a sense of how radiology can aid in establishing the aetiology of bronchiectasis.

PMID: 31508157 [PubMed]

Comparative Analysis of Peptidoglycans From Pseudomonas aeruginosa Isolates Recovered From Chronic and Acute Infections.

Front Microbiol. 2019;10:1868

Authors: Torrens G, Escobar-Salom M, Pol-Pol E, Camps-Munar C, Cabot G, López-Causapé C, Rojo-Molinero E, Oliver A, Juan C

Abstract
Pseudomonas aeruginosa is one of the first causes of acute nosocomial and chronic infections in patients with underlying respiratory pathologies such as cystic fibrosis (CF). It has been proposed that P. aeruginosa accumulates mutations driving to peptidoglycan modifications throughout the development of the CF-associated infection, as a strategy to lower the immune detection hence ameliorating the chronic persistence. As well, some studies dealing with peptidoglycan modifications driving to a better survival within the host have been published in other gram-negatives. According to these facts, the gram-negative peptidoglycan could be considered as a pathogen-associated molecular pattern with very important implications regarding the host's detection-response, worthy to dissect in detail. For this reason, in this work we characterized for the first time the peptidoglycans of three large collections [early CF, late CF and acute infection (bloodstream) P. aeruginosa strains] from qualitative (HPLC), quantitative and inflammatory capacity-related perspectives. The final goal was to identify composition trends potentially supporting the cited strategy of evasion/resistance to the immune system and providing information regarding the differential intrinsic adaptation depending on the type of infection. Although we found several punctual strain-specific particularities, our results indicated a high degree of inter-collection uniformity in the peptidoglycan-related features and the absence of trends amongst the strains studied here. These results suggest that the peptidoglycan of P. aeruginosa is a notably conserved structure in natural isolates regardless of transitory changes that some external conditions could force. Finally, the inverse correlation between the relative amount of stem pentapeptides within the murein sacculus and the resistance to immune lytic attacks against the peptidoglycan was also suggested by our results. Altogether, this work is a major step ahead to understand the biology of peptidoglycan from P. aeruginosa natural strains, hopefully useful in future for therapeutic alternatives design.

PMID: 31507543 [PubMed]

Arachidonic Acid and Docosahexaenoic Acid Metabolites in the Airways of Adults With Cystic Fibrosis: Effect of Docosahexaenoic Acid Supplementation.

Front Pharmacol. 2019;10:938

Authors: Teopompi E, Risé P, Pisi R, Buccellati C, Aiello M, Pisi G, Tripodi C, Fainardi V, Clini E, Chetta A, Rovati GE, Sala A

Abstract
Cystic fibrosis (CF) is an autosomal recessive disorder, caused by genetic mutations in CF transmembrane conductance regulator protein. Several reports have indicated the presence of specific fatty acid alterations in CF patients, most notably decreased levels of plasmatic and tissue docosahexaenoic acid (DHA), the precursor of specialized pro-resolving mediators. We hypothesized that DHA supplementation could restore the production of DHA-derived products and possibly contribute to a better control of the chronic pulmonary inflammation observed in CF subjects. Sputum samples from 15 CF and 10 chronic obstructive pulmonary disease (COPD) subjects were collected and analyzed by LC/MS/MS, and blood fatty acid were profiled by gas chromatography upon lipid extraction and transmethylation. Interestingly, CF subjects showed increased concentrations of leukotriene B4 (LTB4), prostaglandin E2 (PGE2), and 15-hydroxyeicosatetraenoic acid (15-HETE), when compared with COPD patients, whereas the concentrations of DHA metabolites did not differ between the two groups. After DHA supplementation, not only DHA/arachidonic acid (AA) ratio and highly unsaturated fatty acid index were significantly increased in the subjects completing the study (p < 0.05) but also a reduction in LTB4 and 15-HETE was observed, together with a tendency for a decrease in PGE2, and an increase in 17-hydroxy-docosahexaenoic acid (17OH-DHA) levels. At the end of the washout period, LTB4, PGE2, 15-HETE, and 17OH-DHA showed a trend to return to baseline values. In addition, 15-HETE/17OH-DHA ratio in the same sample significantly decreased after DHA supplementation (p < 0.01) when compared with baseline. In conclusion, our results show here that in CF patients, an impairment in fatty acid metabolism, characterized by increased AA-derived metabolites and decreased DHA-derived metabolites, could be partially corrected by DHA supplementation.

PMID: 31507425 [PubMed]

Characterization of Cystic Fibrosis Airway Smooth Muscle Cell Proliferative and Contractile Activities.

Am J Physiol Lung Cell Mol Physiol. 2019 Sep 11;:

Authors: Jang JH, Panariti A, O'Sullivan MJ, Pyrch M, Wong C, Lauzon AM, Martin JG

Abstract
Cystic Fibrosis (CF) is a genetic disease that causes multiple pathologies in the airway. Two major respiratory symptoms of CF are airway hyperresponsiveness (AHR) and airway remodeling. Airway smooth muscle (ASM) is hypothesized to be responsible for these airway dysfunctions as their thickening is involved in remodeling and excessive contraction by the ASM may be behind AHR. It is unclear whether the ASM are intrinsically pathologic, or if micro-environmental influences induce pathological behavior in the ASM. In this study, the contractile and proliferative properties of ASM cells isolated from healthy donor and CF transplant lungs were compared. Proliferation assays showed CF ASM proliferate at a higher rate than healthy cells. Through calcium analysis, no differences in contractile activation was found, however, CF ASM lagged in their reuptake of calcium. The combination CFTR corrector and potentiator, VX-809/770, was used to restore proper CFTR function in CF ASM which resulted in a reduction in proliferation and in a normalization of calcium reuptake kinetics. These results show that improper CFTR function in ASM cause intrinsic changes in their proliferative and contractile properties.

PMID: 31508974 [PubMed - as supplied by publisher]

[Complex care, high cost, and loss of income: frequent issues for families of children and adolescents with rare health conditions].

Cad Saude Publica. 2019 Sep 09;35(9):e00180218

Authors: Pinto M, Madureira A, Barros LBP, Nascimento M, Costa ACCD, Oliveira NV, Albernaz L, Campos DS, Horovitz DDG, Martins AJ, Moreira MCN

Abstract
Estimates point to more than seven thousand rare diseases already identified, representing 6 to 10% of all diseases. In Brazil, a rare disease is defined as one that affects up to 65 persons per 100,000. The quantification of costs for the families of patients with such conditions and their impact on income provides information capable of supporting public policies for these youngsters. The study aimed to estimate the cost and loss of earnings, viewed from the perspective of families of children and adolescents with cystic fibrosis, mucopolysaccharidosis, and osteogenesis imperfecta. The study included 99 families of patients treated at a national referral hospital for rare diseases in Rio de Janeiro, based on the principal caregiver's report. The descriptive data analysis showed that the median direct nonmedical cost for families was BRL 2,156.56 (USD 570) for cystic fibrosis, BRL 1,060.00 (USD 280) for mucopolysaccharidosis, and BRL 1,908.00 (USD 505) for osteogenesis imperfecta. Loss of earnings exceeded 100% for all three diseases. A total of 54% of families fail to receive any social benefits. The estimate of coping costs indicated that 69% of the families had incurred loans and that 22.5% had sold household assets to cope with the treatment costs. Catastrophic expenditures were observed in families dealing with the three diseases. The results unveil costs that are rarely estimated, and not only in the field of rare diseases. The findings point to a major burden on the families' income. It is important to incorporate such studies in the discussion of financing, the incorporation of new technologies, and the supply of health services.

PMID: 31508699 [PubMed - in process]

Creating genetic reports that are understood by nonspecialists: a case study.

Genet Med. 2019 Sep 11;:

Authors: Recchia G, Chiappi A, Chandratillake G, Raymond L, Freeman ALJ

Abstract
PURPOSE: Guidelines recommend that genetic reports should be clear to nonspecialists, including patients. We investigated the feasibility of creating reports for cystic fibrosis carrier testing through a rapid user-centered design process that built on a previously developed generic template. We evaluated the new reports' communication efficacy and effects on comprehension against comparable reports used in current clinical practice.
METHODS: Thirty participants took part in three rounds of interviews. Usability problems were identified and rectified in each round. One hundred ninety-three participants took part in an evaluation of the resulting reports measuring subjective comprehension, risk probability comprehension, perceived communication efficacy, and other factors, as compared with standard reports.
RESULTS: Participants viewing the user-centered reports rated them as clearer, easier to understand, and more effective at communicating key information than standard reports. Both groups ended up with equivalent knowledge of risk probabilities, although we observed differences in how those probabilities were perceived.
CONCLUSION: Our findings demonstrate that by starting with a patient-friendly generic report template and modifying it for specific scenarios with a rapid user-centered design process, reports can be produced that are more effective at communicating key information. The resulting reports are now being implemented into clinical care.

PMID: 31506646 [PubMed - as supplied by publisher]

G-CSF and GM-CSF Modify Neutrophil Functions at Concentrations found in Cystic Fibrosis.

Sci Rep. 2019 Sep 10;9(1):12937

Authors: Castellani S, D'Oria S, Diana A, Polizzi AM, Di Gioia S, Mariggiò MA, Guerra L, Favia M, Vinella A, Leonetti G, De Venuto D, Gallo C, Montemurro P, Conese M

Abstract
The role of colony stimulating factors (CSFs) in cystic fibrosis (CF) circulating neutrophils has not been thoroughly evaluated, considering that the neutrophil burden of lung inflammation in these subjects is very high. The aim of this study was to assess granulocyte-CSF (G-CSF) and granulocyte-macrophage-CSF (GM-CSF) levels in CF patients in various clinical conditions and how these cytokines impact on activation and priming of neutrophils. G-CSF and GM-CSF levels were measured in sputum and serum samples of stable CF patients (n = 21) and in CF patients with acute exacerbation before and after a course of antibiotic therapy (n = 19). CSFs were tested on non CF neutrophils to investigate their effects on reactive oxygen species (ROS) production, degranulation (CD66b, elastase, lactoferrin, MMP-9), and chemotaxis. At very low concentrations found in CF patients (0.005-0.1 ng/ml), both cytokines inhibited ROS production, while higher concentrations (1-5 ng/ml) exerted a stimulatory effect. While either CSF induced elastase and MMP-9 secretion, lactoferrin levels were increased only by G-CSF. Chemotaxis was inhibited by GM-CSF, but was increased by G-CSF. However, when present together at low concentrations, CSFs increased basal and fMLP-stimulated ROS production and chemotaxis. These results suggest the CSF levels that circulating neutrophils face before extravasating into the lungs of CF patients may enhance their function contributing to the airway damage.

PMID: 31506515 [PubMed - in process]

Hypersensitivity pneumonitis in a cystic fibrosis patient.

Occup Med (Lond). 2019 Aug 26;:

Authors: Bellanger AP, Morisse-Pradier H, Reboux G, Scherer E, Pramil S, Dominique S, Millon L

Abstract
Hypersensitivity pneumonitis (HP) is a chronic inflammatory lung disease caused by repeated inhalation of antigenic substances. We present a case of metalworking fluids (MWFs)-HP sensitized to Pseudomonas oleovorans in a cystic fibrosis patient. This case illustrates that HP diagnosis remains challenging, especially in patients with another pulmonary disease, and that serodiagnosis contributes to identifying the precise microorganism involved. It also demonstrates that P. oleovorans is an important secondary aetiological agent in MWF-HP, less known than Mycobacterium immunogenum.

PMID: 31504833 [PubMed - as supplied by publisher]

Cytological appearance of pancreatic cystosis on fine-needle aspiration.

Diagn Cytopathol. 2019 Sep 10;:

Authors: Aly FZ, Mostofizadeh S, Jawaid S

Abstract
A 22-year-old Caucasian male with cystic fibrosis and recently diagnosed insulin-dependent diabetes mellitus underwent magnetic resonance imaging (MRI) and was found to have multiple cystic lesions in the pancreas. Endoscopic ultrasound evaluation revealed multiple macro- and microcystic components without mural nodules. One of the cysts in the body of the pancreas was in clear direct communication with the nondilated main pancreatic duct. Fine-needle aspiration (FNA) of two cysts was performed and showed foamy macrophages and rare ductal as well as acinar cells. Cell blocks showed nonpolarizable pink crystalloid material and small nonlaminated concretions consistent with inspissated secretions. Special stains for chymotrypsin and trypsin highlighted the acinar cells. Periodic acid Schiff, with and without diastase, was negative. Biopsy of the cyst wall showed ductal epithelial cells with underlying fibrotic stroma. This is the first description of the FNA appearance of pancreatic cystosis. We discuss the cytological differential diagnosis of cystic lesions of the pancreas and the biochemical as well as imaging findings used to arrive at the diagnosis.

PMID: 31503419 [PubMed - as supplied by publisher]