Impact of Coexistence Phenotype Between Staphylococcus aureus and Pseudomonas aeruginosa Isolates on Clinical Outcomes Among Cystic Fibrosis Patients.

Front Cell Infect Microbiol. 2020;10:266

Authors: Briaud P, Bastien S, Camus L, Boyadjian M, Reix P, Mainguy C, Vandenesch F, Doléans-Jordheim A, Moreau K

Abstract
Staphylococcus aureus (SA) is the major colonizer of the lungs of cystic fibrosis (CF) patients during childhood and adolescence. As patients age, the prevalence of SA decreases and Pseudomonas aeruginosa (PA) becomes the major pathogen infecting adult lungs. Nonetheless, SA remains significant and patients harboring both SA and PA are frequently found in the worldwide cohort. The overall impact of co-infection remains controversial. Furthermore, co-infecting isolates may compete or coexist. The aim of this study was to analyse if co-infection and the coexistence of SA and PA could lead to worse clinical outcomes. The clinical and bacteriological data of 212 Lyon CF patients were collected retrospectively, and patients were ranked into three groups, SA only (n = 112), PA only (n = 48) or SA plus PA (n = 52). In addition, SA and PA isolates from co-infected patients were tested in vitro to define their interaction profile. Sixty five percent (n = 34) of SA/PA pairs coexist. Using univariate and multivariate analysis, we confirm that SA patients have a less severe clinical condition than others, and PA induces a poor outcome independently of the presence of SA. Regarding co-infection, no significant difference in clinical outcomes was observed between patients with coexisting pairs and patients with competitive pairs. However, when compared to SA mono-infected patients, patients with coexisting pair presented higher frequency and length of hospitalizations and more exacerbations. We suggest that coexistence between SA and PA may be an important step in the natural history of lung bacterial colonization within CF patients.

PMID: 32582568 [PubMed - in process]

The Natural Polypeptides as Significant Elastase Inhibitors.

Front Pharmacol. 2020;11:688

Authors: Ahmad S, Saleem M, Riaz N, Lee YS, Diri R, Noor A, Almasri D, Bagalagel A, Elsebai MF

Abstract
Human neutrophil elastase (HNE) is a major cause of the destruction of tissues in cases of several different chronic andinflammatory diseases. Overexpression of the elastase enzyme plays a significant role in the pathogenesis of various diseases including chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome, rheumatoid arthritis, the rare disease cyclic hematopoiesis (or cyclic neutropenia), infections, sepsis, cystic fibrosis, myocardial ischemia/reperfusion injury and asthma, inflammation, and atherosclerosis. Human neutrophil elastase is secreted by human neutrophils due to different stimuli. Medicine-based inhibition of the over-activation of neutrophils or production and activity of elastase have been suggested to mend inflammatory diseases. Although the development of new elastase inhibitors is an essential strategy for treating the different inflammatory diseases, it has been a challenge to specifically target the activity of elastase because of its overlapping functions with those of other serine proteases. This review article highlights the reported natural polypeptides as potential inhibitors of elastase enzyme. The mechanism of action, structural features, and activity of the polypeptides have also been correlated wherever they were available.

PMID: 32581778 [PubMed]

A fly model of cystic fibrosis.

Lab Anim (NY). 2020 Jul;49(7):196

Authors: Le Bras A

PMID: 32581332 [PubMed - in process]

Pediatric lung transplantation: Dynamics of the microbiome and bronchiolitis obliterans in cystic fibrosis.

J Heart Lung Transplant. 2020 May 19;:

Authors: Metwally AA, Ascoli C, Turturice B, Rani A, Ranjan R, Chen Y, Schott C, Faro A, Ferkol TW, Finn PW, Perkins DL

Abstract
BACKGROUND: Compositional changes in the microbiome are associated with the development of bronchiolitis obliterans (BO) after lung transplantation (LTx) in adults with cystic fibrosis (CF). The association between the lower airway bacterial community and BO after LTx in children with CF remains largely unexplored and is possibly influenced by frequent antibiotic therapy. The objectives of this study were to examine the relationship between bacterial community dynamics and the development of BO and analyze antibiotic resistance trends in children after LTx for CF.
METHODS: For 3 years from the time of transplant, 12 LTx recipients were followed longitudinally, with 5 subjects developing BO during the study period. A total of 82 longitudinal bronchoalveolar lavage samples were collected during standard of care bronchoscopies. Metagenomic shotgun sequencing was performed on the extracted microbial DNA from bronchoalveolar lavage specimens. Taxonomic profiling was constructed using WEVOTE pipeline. The longitudinal association between development of BO and temporal changes in bacterial diversity and abundance were evaluated with MetaLonDA. The analysis of antibiotic resistance genes was performed with the ARGs-OAP v2.0 pipeline.
RESULTS: All recipients demonstrated a Proteobacteria-predominant lower airways community. Temporal reduction in bacterial diversity was significantly associated with the development of BO and associated with neutrophilia and antibiotic therapy. Conversely, an increasing abundance of the phylum Actinobacteria and the orders Neisseriales and Pseudonocardiales in the lower airways was significantly associated with resilience to BO. A more diverse bacterial community was related to a higher expression of multidrug resistance genes and increased proteobacterial abundance.
CONCLUSIONS: Decreased diversity within bacterial communities may suggest a contribution to pediatric lung allograft rejection in CF.

PMID: 32580896 [PubMed - as supplied by publisher]

Le COVID-19 et la mucoviscidose : aussi vite que possible mais aussi lentement que nécessaire ?

Rev Med Suisse. 2020 06 17;16(698):1227

Authors: Fellrath JM, Sauty A

PMID: 32558450 [PubMed - indexed for MEDLINE]

FACTORS ASSOCIATED TO QUALITY OF LIFE IN CHILDREN AND ADOLESCENTS WITH CYSTIC FIBROSIS.

Rev Paul Pediatr. 2020;38:e2018397

Authors: Santana NN, Chaves CRMM, Gonçalves CP, Gomes Junior SCDS

Abstract
OBJECTIVE: To verify the association between quality of life, functional capacity and clinical and nutritional status in children and adolescents with cystic fibrosis (CF).
METHODS: Cross-sectional study, including patients from eight to 18 years old with CF. Quality of life, functional capacity, nutritional status and clinical status were evaluated with the Cystic Fibrosis Questionnaire; the 6-minute walk test (6MWT) and manual gripping force (MGF); the height percentiles for age and body mass index for age and respiratory function test, respectively. Pearson and Spearman correlation tests and logistic regression were used to analyze the data.
RESULTS: A total of 45 patients, 13.4±0.5 years old, 60% female, 60% colonized by Pseudomonas aeruginosa and 57.8% with at least one F508del mutation participated in the study. When assessing the perception of quality of life, the weight domain reached the lowest values, and the digestive domain, the highest. In the pulmonary function test, the forced expiratory volume of the first second was 77.3±3.3% and the 6MWT and MGF presented values within the normal range. There was an association between quality of life and functional capacity, nutritional status and clinical status of CF patients.
CONCLUSIONS: The study participants had good clinical conditions and satisfactory values of functional capacity and quality of life. The findings reinforce that the assessment of quality of life may be important for clinical practice in the management of treatment.

PMID: 32578674 [PubMed - in process]

Decades of cough: delayed recognition of atypical cystic fibrosis in an adult patient.

JRSM Open. 2020 Jun;11(6):2054270420921003

Authors: Chandel A, Pak K, Dooley S, Salazar K

Abstract
We present a case of a 30-year-old male diagnosed with atypical cystic fibrosis. This report demonstrates the heterogeneity of the presentation of this common genetic disease.

PMID: 32577293 [PubMed]

Genotypic and Phenotypic Diversity of Staphylococcus aureus Isolates from Cystic Fibrosis Patient Lung Infections and Their Interactions with Pseudomonas aeruginosa.

mBio. 2020 Jun 23;11(3):

Authors: Bernardy EE, Petit RA, Raghuram V, Alexander AM, Read TD, Goldberg JB

Abstract
Staphylococcus aureus has recently overtaken Pseudomonas aeruginosa as the most commonly recognized bacterial pathogen that infects the respiratory tracts of individuals with the genetic disease cystic fibrosis (CF) in the United States. Most studies of S. aureus in CF patient lung infections have focused on a few isolates, often exclusively laboratory-adapted strains, and how they are killed by P. aeruginosa Less is known about the diversity of S. aureus CF patient lung isolates in terms of both their virulence and their interaction with P. aeruginosa To begin to address this gap, we recently sequenced 64 clinical S. aureus isolates and a reference isolate, JE2. Here, we analyzed the antibiotic resistance genotypes, sequence types, clonal complexes, spa types, agr types, and presence/absence of other known virulence factor genes of these isolates. We hypothesized that virulence phenotypes of S. aureus, namely, toxin production and the mucoid phenotype, would be lost in these isolates due to adaptation in the CF patient lung. In contrast to these expectations, we found that most isolates can lyse both rabbit and sheep blood (67.7%) and produce polysaccharide (69.2%), suggesting that these phenotypes were not lost during adaptation to the CF lung. We also identified three distinct phenotypic groups of S. aureus based on their survival in the presence of nonmucoid P. aeruginosa laboratory strain PAO1 and its mucoid derivative. Altogether, our work provides greater insight into the diversity of S. aureus isolates from CF patients, specifically the distribution of important virulence factors and their interaction with P. aeruginosa, all of which have implications in patient health.IMPORTANCE Staphylococcus aureus is now the most frequently detected recognized pathogen in the lungs of individuals who have cystic fibrosis (CF) in the United States, followed closely by Pseudomonas aeruginosa When these pathogens are found to coinfect the CF lung, patients have a significantly worse prognosis. While P. aeruginosa has been rigorously studied in the context of bacterial pathogenesis in CF, less is known about S. aureus Here, we present an in-depth study of 64 S. aureus clinical isolates from CF patients, for which we investigated genetic diversity utilizing whole-genome sequencing, virulence phenotypes, and interactions with P. aeruginosa We found that S. aureus isolated from CF lungs are phylogenetically diverse; most retain known virulence factors and vary in their interactions with P. aeruginosa (i.e., they range from being highly sensitive to P. aeruginosa to completely tolerant to it). Deepening our understanding of how S. aureus responds to its environment and other microbes in the CF lung will enable future development of effective treatments and preventative measures against these formidable infections.

PMID: 32576671 [PubMed - in process]

High-Resolution Longitudinal Dynamics of the Cystic Fibrosis Sputum Microbiome and Metabolome through Antibiotic Therapy.

mSystems. 2020 Jun 23;5(3):

Authors: Raghuvanshi R, Vasco K, Vázquez-Baeza Y, Jiang L, Morton JT, Li D, Gonzalez A, DeRight Goldasich L, Humphrey G, Ackermann G, Swafford AD, Conrad D, Knight R, Dorrestein PC, Quinn RA

Abstract
Microbial diversity in the cystic fibrosis (CF) lung decreases over decades as pathogenic bacteria such as Pseudomonas aeruginosa take over. The dynamics of the CF microbiome and metabolome over shorter time frames, however, remain poorly studied. Here, we analyze paired microbiome and metabolome data from 594 sputum samples collected over 401 days from six adult CF subjects (subject mean = 179 days) through periods of clinical stability and 11 CF pulmonary exacerbations (CFPE). While microbiome profiles were personalized (permutational multivariate analysis of variance [PERMANOVA] r 2 = 0.79, P < 0.001), we observed significant intraindividual temporal variation that was highest during clinical stability (linear mixed-effects [LME] model, P = 0.002). This included periods where the microbiomes of different subjects became highly similar (UniFrac distance, <0.05). There was a linear increase in the microbiome alpha-diversity and in the log ratio of anaerobes to pathogens with time (n = 14 days) during the development of a CFPE (LME P = 0.0045 and P = 0.029, respectively). Collectively, comparing samples across disease states showed there was a reduction of these two measures during antibiotic treatment (LME P = 0.0096 and P = 0.014, respectively), but the stability data and CFPE data were not significantly different from each other. Metabolome alpha-diversity was higher during CFPE than during stability (LME P = 0.0085), but no consistent metabolite signatures of CFPE across subjects were identified. Virulence-associated metabolites from P. aeruginosa were temporally dynamic but were not associated with any disease state. One subject died during the collection period, enabling a detailed look at changes in the 194 days prior to death. This subject had over 90% Pseudomonas in the microbiome at the beginning of sampling, and that level gradually increased to over 99% prior to death. This study revealed that the CF microbiome and metabolome of some subjects are dynamic through time. Future work is needed to understand what drives these temporal dynamics and if reduction of anaerobes correlate to clinical response to CFPE therapy.IMPORTANCE Subjects with cystic fibrosis battle polymicrobial lung infections throughout their lifetime. Although antibiotic therapy is a principal treatment for CF lung disease, we have little understanding of how antibiotics affect the CF lung microbiome and metabolome and how much the community changes on daily timescales. By analyzing 594 longitudinal CF sputum samples from six adult subjects, we show that the sputum microbiome and metabolome are dynamic. Significant changes occur during times of stability and also through pulmonary exacerbations (CFPEs). Microbiome alpha-diversity increased as a CFPE developed and then decreased during treatment in a manner corresponding to the reduction in the log ratio of anaerobic bacteria to classic pathogens. Levels of metabolites from the pathogen P. aeruginosa were also highly variable through time and were negatively associated with anaerobes. The microbial dynamics observed in this study may have a significant impact on the outcome of antibiotic therapy for CFPEs and overall subject health.

PMID: 32576651 [PubMed]

Lung clearance index-triggered intervention in children with cystic fibrosis - A randomised pilot study.

J Cyst Fibros. 2020 Jun 20;:

Authors: Voldby C, Green K, Kongstad T, Ring AM, Sandvik RM, Skov M, Buchvald F, Pressler T, Nielsen KG

Abstract
HYPOTHESIS: Using increase in the lung clearance index (LCI) as a trigger for bronchoalveolar lavage (BAL) and associated antimicrobial treatment might benefit clinical outcomes in children with cystic fibrosis (CF).
METHODS: A 2-year, longitudinal, interventional, randomized, controlled pilot study with quarterly visits in 5-18 years old children with CF. LCI and z-scores for the forced expired volume in 1 s (zFEV1) and body mass index (zBMI) were obtained at every visit, CF Questionnaire-revised (CFQ-R) yearly and BAL and chest computed tomography at first and last visit. Children in the intervention group had BAL performed if LCI increased >1 unit from a fixed baseline value established at first visit. If the presence of a pathogen was documented in the BAL fluid, treatment was initiated/altered accordingly.
RESULTS: Twenty-nine children with CF were randomized to the control (n = 14) and intervention group (n = 15). The median (interquartile range) number of BAL procedures per child was 2.5 (2.0; 3.0) and 6.0 (4.0; 7.0) in the control and intervention group, respectively. There was no significant difference between groups in slope for the primary outcome LCI; difference was 0.21 (95% confidence interval: -0.45; 0.88) units/year. Likewise, there was no significant difference between groups in slope for the secondary outcomes zFEV1, zBMI, CFQ-R respiratory symptom score and the proportion of total disease and trapped air on chest computed tomography.
CONCLUSIONS: LCI-triggered BAL and associated antimicrobial treatment did not benefit clinical outcomes in a small cohort of closely monitored school-age children with CF.

PMID: 32576447 [PubMed - as supplied by publisher]

Differential Chloride Secretory Capacity in Transepithelial Ion Transport Properties in Chronic Rhinosinusitis.

Am J Rhinol Allergy. 2020 Jun 23;:1945892420930975

Authors: McCormick J, Hoffman K, Thompson H, Skinner D, Zhang S, Grayson J, Illek B, Cho DY, Woodworth BA

Abstract
BACKGROUND: Epithelial ion transport regulates hydration of airway mucosal surfaces, and thus promotes effective mucociliary clearance (MCC). Decreased transepithelial Cl- transport may contribute to epithelial dysfunction by abrogating MCC and increasing mucus viscosity in chronic rhinosinusitis (CRS). The objective of the current study is to evaluate Cl- channel transport properties from cultures of human sinonasal epithelia.
METHODS: Human sinonasal epithelia (HSNE) from patients undergoing sinus surgery were cultured at an air-liquid interface to confluence and full differentiation. The epithelial monolayers were mounted in Ussing Chambers to investigate pharmacological manipulation of ion transport. Epithelial Na+ channel (via Amiloride), CFTR (via forskolin), and Ca2+-activated Cl- channel (CaCC, via UTP) transport were investigated among three different patient groups: Control, CRS and CRS with polyposis. CFTR mRNA levels were evaluated with quantitative RT-PCR.
RESULTS: HSNE cultures from 18 patients (Control = 9, CRS = 6, CRS with polyposis = 3) were evaluated in 142 experiments. Summary data from the 18 patients demonstrated that stimulated CFTR-mediated anion transport (Δ ISC) was significantly lower with CRS (7.58+/-2.24 µA/cm2) compared to control (25.86+/-3.44 µA/cm2) and CRS with polyposis (20.16+/-4.0 µA/cm2) (p = 0.004). No statistically significant difference was found for CaCC anion transport between groups (p = 0.39). Significantly decreased mRNA (relative expression) was noted in CRS cultures (CRS = 40.83+/-1.76 vs. control = 116.2+/-24.27, p = 0.03).
CONCLUSIONS: A substantial decrease in the Cl- secretory capacity of HSNE monolayers was demonstrated in CRS subjects. Data suggest that CFTR may contribute more to abnormal ion transport in CRS than CaCC.

PMID: 32576027 [PubMed - as supplied by publisher]

Fetal Meconium Peritonitis - Prenatal Findings and Postnatal Outcome: A Case Series, Systematic Review, and Meta-Analysis.

Ultraschall Med. 2020 Jun 23;:

Authors: Shinar S, Agrawal S, Ryu M, Van Mieghem T, Daneman A, Ryan G, Zani A, Chiu P, Chitayat D

Abstract
PURPOSE:  To describe the postnatal outcome of fetal meconium peritonitis and identify prenatal predictors of neonatal surgery.
METHODS:  We retrospectively reviewed all fetuses with ultrasound findings suspicious for meconium peritonitis at a single center over a 10-year period. A systematic review and meta-analysis were then performed pooling our results with previous studies assessing prenatally diagnosed meconium peritonitis and postnatal outcome. Prenatal sonographic findings were analyzed to identify predictors for postnatal surgery.
RESULTS:  34 cases suggestive of meconium peritonitis were diagnosed at our center. These were pooled with cases from 14 other studies yielding a total of 244 cases. Postnatal abdominal surgery was required in two thirds of case (66.5 %). The strongest predictor of neonatal surgery was meconium pseudocyst (OR [95 % CI] 6.75 [2.53-18.01]), followed by bowel dilation (OR [95 % CI] 4.17 [1.93-9.05]) and ascites (OR [95 % CI] 2.57 [1.07-5.24]). The most common cause of intestinal perforation and meconium peritonitis, found in 52.2 % of the cases, was small bowel atresia. Cystic fibrosis was diagnosed in 9.8 % of cases. Short-term neonatal outcomes were favorable, with a post-operative mortality rate of 8.1 % and a survival rate of 100 % in neonates not requiring surgery.
CONCLUSION:  Meconium pseudocysts, bowel dilation, and ascites are prenatal predictors of neonatal surgery in cases of meconium peritonitis. Fetuses with these findings should be delivered in centers with pediatric surgery services. Though the prognosis is favorable, cystic fibrosis complicates postnatal outcomes.

PMID: 32575129 [PubMed - as supplied by publisher]

CFTR deficiency causes cardiac dysplasia during zebrafish embryogenesis and is associated with dilated cardiomyopathy.

Mech Dev. 2020 Jun 20;:103627

Authors: Liu Y, Lin Z, Liu M, Liao H, Chen Y, Zhang X, Chan HC, Zhou B, Rao L, Sun H

Abstract
Mutations in the CFTR gene cause cystic fibrosis (CF) with myocardial dysfunction. However, it remains unknown whether CF-related heart disease is a secondary effect of pulmonary disease, or an intrinsic primary defect in the heart. Here, we used zebrafish, which lack lung tissue, to investigate the role of CFTR in cardiogenesis. Our findings demonstrated that the loss of CFTR impairs cardiac development from the cardiac progenitor stage, resulting in cardiac looping defects, a dilated atrium, pericardial edema, and a decrease in heart rate. Furthermore, we found that cardiac development was perturbed in wild-type embryos treated with a gating-specific CFTR channel inhibitor, CFTRinh-172, at the blastula stage of development, but not at later stages. Gene expression analysis of blastulas indicated that transcript levels, including mRNAs associated with cardiovascular diseases, were significantly altered in embryos derived from cftr mutants relative to controls. To evaluate the role of CFTR in human heart failure, we performed a genetic association study on individuals with dilated cardiomyopathy and found that the I556V mutation in CFTR, which causes a channel defect, was associated with the disease. Similar to other well-studied channel-defective CFTR mutants, CFTR I556V mRNA failed to restore cardiac dysplasia in mutant embryos. The present study revealed an important role for the CFTR ion channel in regulating cardiac development during early embryogenesis, supporting the hypothesis that CF-related heart disease results from an intrinsic primary defect in the heart.

PMID: 32574800 [PubMed - as supplied by publisher]

Highlights From the 2019 North American Cystic Fibrosis Conference.

Pediatr Pulmonol. 2020 Jun 23;:

Authors: Hoppe JE, Guimbellot J, Martiniano SL, Toprak D, Davis C, Daines CL, Muhlebach MS, Esther CR, Dellon EP

Abstract
The 33rd annual North American Cystic Fibrosis Conference (NACFC) was held in Nashville, Tennessee on October 31-November 2, 2019. Abstracts of presentations from the conference were published in a supplement to Pediatric Pulmonology 1 . This review briefly summarizes presentations in several major topic areas at the conference: pathophysiology and basic science of cystic fibrosis (CF) lung disease; clinical trials; clinical quality improvement; microbiology and treatment of infection; and transition, advanced lung disease and transplant, mental health and psychosocial concerns. The review is intended to highlight several areas and is not a comprehensive summary of the conference. Citations from the conference are by first author and abstract number or symposium number, as designated in the supplement. This article is protected by copyright. All rights reserved.

PMID: 32573948 [PubMed - as supplied by publisher]

Cytoskeleton regulators CAPZA2 and INF2 associate with CFTR to control its plasma membrane levels under EPAC1 activation.

Biochem J. 2020 Jun 23;:

Authors: Santos JD, Pinto FR, Ferreira JF, Amaral MD, Zaccolo M, Farinha CM

Abstract
Cystic Fibrosis (CF), the most common lethal autosomic recessive disorder among Caucasians, is caused by mutations in the gene encoding the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein, a cAMP-regulated chloride channel expressed at the apical surface of epithelial cells. Cyclic AMP regulates both CFTR channel gating through a protein kinase A (PKA)-dependent process and plasma membane (PM) stability through activation of the exchange protein directly activated by cAMP1 (EPAC1). This cAMP effector, when activated promotes the NHERF1:CFTR interaction leading to an increase in CFTR at the PM by decreasing its endocytosis. Here, we used protein interaction profiling and bioinformatic analysis to identify proteins that interact with CFTR under EPAC1 activation as possible regulators of this CFTR PM anchoring. We identified an enrichment in cytoskeleton related proteins among which we characterized CAPZA2 and INF2 as regulators of CFTR trafficking to the PM. We found that CAPZA2 promotes wt-CFTR trafficking under EPAC1 activation at the PM whereas reduction of INF2 levels leads to a similar trafficking promotion effect. These results suggest that CAPZA2 is a positive regulator and INF2 a negative one for the increase of CFTR at the PM after an increase of cAMP and concomitant EPAC1 activation. Identifying the specific interactions involving CFTR and elicited by EPAC1 activation provides novel insights into late CFTR trafficking, insertion and/or stabilization at the PM and highlighs new potential therapeutic targets to tackle CF disease.

PMID: 32573649 [PubMed - as supplied by publisher]

Italian suggestions for pulmonary rehabilitation in COVID-19 patients recovering from acute respiratory failure: results of a Delphi process.

Monaldi Arch Chest Dis. 2020 Jun 23;90(2):

Authors: Vitacca M, Lazzeri M, Guffanti E, Frigerio P, D'Abrosca F, Gianola S, Carone M, Paneroni M, Ceriana P, Pasqua F, Banfi P, Gigliotti F, Simonelli C, Cirio S, Rossi V, Beccaluva CG, Retucci M, Santambrogio M, Lanza A, Gallo F, Fumagalli A, Mantero M, Castellini G, Calabrese M, Castellana G, Volpato E, Ciriello M, Garofano M, Clini E, Ambrosino N, Arir Associazione Riabilitatori dell'Insufficienza Respiratoria Sip Società Italiana di Pneumologia Aifi Associazione Italiana Fisioterapisti And Sifir Società Italiana di Fisioterapia E Riabilitazione OBOAAIPO

Abstract
There is a need of consensus about the pulmonary rehabilitation (PR) in patients with COVID-19 after discharge from acute care. To facilitate the knowledge of the evidence and its translation into practice, we developed suggestions based on experts' opinion. A steering committee identified areas and questions sent to experts. Other international experts participated to a RAND Delphi method in reaching consensus and proposing further suggestions. Strong agreement in suggestions was defined when the mean agreement was >7 (1 = no agreement and 9 = maximal agreement). Panelists response rate was >95%. Twenty-three questions from 4 areas: Personnel protection equipment, phenotypes, assessments, interventions, were identified and experts answered with 121 suggestions, 119 of which received high level of concordance. The evidence-based suggestions provide the clinicians with current evidence and clinical experts opinion. This framework can be used to facilitate clinical decision making within the context of the individual patient. Further studies will evaluate the clinical usefulness of these suggestions.

PMID: 32573175 [PubMed - in process]

Determining the Suitability of Registries for Embedding Clinical Trials in the United States: A Project of the Clinical Trials Transformation Initiative.

Ther Innov Regul Sci. 2020 Jun 22;:

Authors: Mikita JS, Mitchel J, Gatto NM, Laschinger J, Tcheng JE, Zeitler EP, Swern AS, Flick ED, Dowd C, Lystig T, Calvert SB

Abstract
BACKGROUND: Patient registries are organized systems that use observational methods to collect uniform data on specified outcomes in a population defined by a particular disease, condition, or exposure. Data collected in registries often coincide with data that could support clinical trials. Integrating clinical trials within registries to create registry-embedded clinical trials offers opportunities to reduce duplicative data collection, identify and recruit patients more efficiently, decrease time to database lock, accelerate time to regulatory decision-making, and reduce clinical trial costs. This article describes a project of the Clinical Trials Transformation Initiative (CTTI) intended to help clinical trials researchers determine when a registry could potentially serve as the platform for the conduct of a clinical trial.
METHODS: Through a review of registry-embedded clinical trials and commentaries, semi-structured interviews with experts, and a multi-stakeholder expert meeting, the project team addressed how to identify and describe essential registry characteristics, practices, and processes required to for conducting embedded clinical trials intended for regulatory submissions in the United States.
RESULTS: Recommendations, suggested practices, and decision trees that facilitate the assessment of whether a registry is suitable for embedding clinical trials were developed, as well as considerations for the design of new registries. Essential registry characteristics include relevancy, robustness, reliability, and assurance of patient protections.
CONCLUSIONS: The project identifies a clear role for registries in creating a sustainable and reusable infrastructure to conduct clinical trials. Adoption of these recommendations will facilitate the ability to perform high-quality and efficient prospective registry-based clinical trials.

PMID: 32572772 [PubMed - as supplied by publisher]

Diagnostic performance and role of the contrast enema for low intestinal obstruction in neonates.

Pediatr Surg Int. 2020 Jun 23;:

Authors: Baad M, Delgado J, Dayneka JS, Anupindi SA, Reid JR

Abstract
PURPOSE: We aim to evaluate the diagnostic performance and relationship between clinical characteristics, imaging findings, and final diagnosis for the neonatal contrast enema (CE).
METHODS: Retrospective 10-year review of all neonatal CEs including imaging findings, clinical information, indication, and final diagnosis from discharge summaries, surgical reports, and pathology (reference standard). Two blinded pediatric radiologists reinterpreted 366 CEs for obstruction, microcolon, rectosigmoid index (RSI), serrations, meconium, ileal cut-off, transition zone, diagnosis, and level of confidence. CE diagnostic performance was calculated versus reference standard.
RESULTS: Diagnoses included Hirschsprung disease (HD) (15.8%), small left colon syndrome (14.8%), small intestinal atresia/colonic atresia (SIA/CA) (12.6%), meconium ileus (MI) (4.4%), and normal (48.9%). CE had a moderate specificity (87.7%) and low sensitivity (65.5%) for HD; abnormal RSI and serrations showed high specificities (90.3%, 97.4%) but low sensitivities (46.6%, 17.2%). CE showed high specificity (97.4%) and low sensitivity (56.3%) for MI blinded to cystic fibrosis status. Microcolon was specific (96.6%) but not sensitive (68.8%) for MI. CE showed highest PPV (73.1%) (specificity 95.6%, sensitivity 82.6%) for SIA/CA. Microcolon with an abrupt cut-off was specific (99.1%) but not sensitive (41.3%) for atresias.
CONCLUSION: Neonatal CE demonstrates high specificities and low to moderate sensitivities across all diagnoses, with lowest performance in HD.
CLINICAL TRIAL REGISTRATION: None.

PMID: 32572600 [PubMed - as supplied by publisher]

Single Lung Transplantation With Concomitant Cardiac Surgery in a Patient With Cystic Fibrosis: A Case Report.

Transplant Proc. 2020 Jun 19;:

Authors: Antończyk R, Urlik M, Latos M, Pandel A, Gawęda M, Nęcki M, Kręt M, Przybyłowski P, Zembala M, Ochman M, Stącel T

Abstract
BACKGROUND: Cystic fibrosis is a congenital, progressive disease affecting many organs. It frequently leads to severe respiratory failure, which can be treated by means of a double lung transplantation. Single lung transplantation is justified only in certain cases.
CASE REPORT: This is a case report describing a 20-year-old female patient who became the recipient of a single lung transplant as a result of cystic fibrosis. The transplant was performed during cardiothoracic surgery, which included an intervention in the right atrium. At the age of 14, the patient underwent left pneumonectomy. In addition, the patient had a percutaneous endoscopic gastrostomy placed and a vascular port implanted. During preoperative evaluation, she presented with clinical symptoms of chronic respiratory failure. The patient was approved for lung transplantation at the age of 16. After 2 years on the national lung transplant waiting list, in 2018, the patient underwent right lung transplantation and removal of numerous thrombi in the right atrium during 1 procedure. This surgery was accomplished with the use of extracorporeal circulation, which is an extracorporeal membrane oxygenator combined with cardiopulmonary bypass. The patient was discharged 3 weeks after the procedure in good general condition. Presently, her pulmonary function is excellent and she presents with normal respiratory capacity.
CONCLUSIONS: Patients with cystic fibrosis often require double lung transplantation. Under normal circumstances, performing only a single lung transplantation would be considered medical malpractice. However, in certain cases, a single lung transplant is a life-saving procedure.

PMID: 32571702 [PubMed - as supplied by publisher]

Associations between Pretend Play, Psychological Functioning and Coping Strategies in Pediatric Chronic Diseases: A Cross-Illness Study.

Int J Environ Res Public Health. 2020 Jun 18;17(12):

Authors: Di Riso D, Cambrisi E, Bertini S, Miscioscia M

Abstract
Children with chronic illnesses are called to undertake complicated processes of adjustment and re-organization in their daily lives; as a result, they could experience several internalizing problems. Symbolic play could be a useful way to cope with these difficulties. The main aim of this paper is to assess pretend play, coping, and psychological symptoms in three groups of school-aged children with pediatric chronic diseases. The study involved 44 Italian school-aged, chronically ill children: 16 with type 1 diabetes mellitus (T1DM), 12 with cystic fibrosis (CF), and 15 with Leukemia. All patients were assessed by the Affect in Play Scale-Brief version (APS-Br), and the Children's Coping Strategies Checklist-Revision1 (CCSC-R1). Children with T1DM and CF also completed the Separation Anxiety Symptom Inventory for Children (SASI-C) and the Strengths and Difficulties Questionnaire (SDQ)-children's version. Cohen's d (effect size) was applied between clinical and normative samples, and it showed a more organized play (APS-BR), but a more negative affect tone, comfort, and frequency of affect expression. Comparing APS-BR and CCSC-R1 rates between the three groups, significant differences were found for all the APS-BR dimensions, except for tone, and for CCSC-R1 seeking understanding. Comparing SASI-C score between T1DM and CF, higher scores were found for children with CF. In the end, correlations between all dimensions highlighted several relationships between play, coping, and adjustment problems for children with T1DM, and relationship between affect play and all variables for children with CF. Symbolic play helps chronically ill children to express emotions; helping them, as well as clinicians, to understand the difficulties caused by chronic conditions, and to cope with them.

PMID: 32570747 [PubMed - in process]