Pediatr Pulmonol. 2022 Nov 9. doi: 10.1002/ppul.26214. Online ahead of print.

ABSTRACT

OBJECTIVE(S): To determine the association of Clostridioides difficile Infection (CDI) with in-hospital mortality, Length of Stay [LOS], and hospital charges among pediatric Cystic Fibrosis (CF) hospitalizations using a large nationally representative pediatric hospital database.

STUDY DESIGN: We identified Cystic Fibrosis-related hospitalizations during the years 1997 to 2016 in the Kids' Inpatient Database [KID] and compared in-hospital mortality, Length of Stay [LOS], and hospital charges among hospitalizations with and without a coexisting diagnosis of C. difficile using logistic regression models for mortality and general linear models with gamma distribution and logarithmic transformation for LOS and hospital charges. We also evaluated temporal trends in the proportion of CF hospitalizations with concomitant CDI using data published triennially RESULTS: We analyzed 21, 616 pediatric CF hospitalizations between the years 1997 to 2016 and found a total of 240 (1.1%) hospitalizations with concurrent CDI diagnosis. Adjusted analyses demonstrated an association of CDI with increased mortality (OR 5.2, 95% 95% CI 2.5-10.7), longer LOS (46.5% increment, 95% CI 36.0-57.1), and higher charges (65.8% increment, 95% CI 53.5-78.1) for all comparisons. The proportion of CF hospitalizations with CDI increased over time from 0.64% in 1997 to 1.73% in 2016 (p<0.001).

CONCLUSION(S): As CDI is associated with excess mortality, LOS, and cost in children hospitalized for CF, a healthy level of suspicion for CDI may be needed in patients with CF in the appropriate clinical context. Efforts to prevent, diagnose, and treat CDI may improve hospital outcomes among children with CF. This article is protected by copyright. All rights reserved.

PMID:36349995 | DOI:10.1002/ppul.26214

Pediatr Pulmonol. 2022 Nov 9. doi: 10.1002/ppul.26236. Online ahead of print.

ABSTRACT

This report describes a case of an 11-year-old Chinese boy with cystic fibrosis (CF) bearing the c.1521_1523delCTT/c.3874-4522A>G genotype, an extremely rare CF genotype in the Chinese population. Notably, the deep intron mutation c.3874-4522A>G, which has mainly been reported in patients with phenotypically mild CF, is identified here for the first time in a Chinese patient with severe CF. In the case discussed here, the c.3874-4522A>G mutation was associated with severe pulmonary disease with early symptoms onset, progressive bronchiectasis, recurrent airway infection with both P. aeruginosa and methicillin-resistant Staphylococcus aureus, rapid decline of lung function and poor weight gain. Despite intensive hospital-based pulmonary care and optimized therapy, the child died of cardiopulmonary failure three months after discharge. This article is protected by copyright. All rights reserved.

PMID:36349818 | DOI:10.1002/ppul.26236

Pediatr Pulmonol. 2022 Nov 9. doi: 10.1002/ppul.26238. Online ahead of print.

ABSTRACT

Children with cystic fibrosis have ongoing and emerging needs as they progress into adulthood. The literature has identified that some of these needs are not fully being met. The profession of occupational therapy is uniquely equipped and trained to address a variety of needs that children with cystic fibrosis experience during daily life engagement, potentially filling this gap in services. This includes addressing areas of motor performance, health management, medication management, and quality of life. Despite this, occupational therapists are rarely consulted or included in patient care plans. The goal of this letter is to increase awareness and understanding of the contributions that occupational therapy can make to the care of children with cystic fibrosis. This article is protected by copyright. All rights reserved.

PMID:36349747 | DOI:10.1002/ppul.26238

Pediatr Pulmonol. 2022 Nov 8. doi: 10.1002/ppul.26241. Online ahead of print.

ABSTRACT

The cannabis plant is the most used federally illegal drug in the United States and is widely used by adolescents. Cystic Fibrosis (CF) has significant impact on the life experiences and development of the adolescent, as well as the prevalence and complex effects of cannabis on the body and mind. All health professionals who take care of adolescents with CF, including primary care and mental health providers and staff, should be aware of the factors impacting cannabis use in CF and ways to ameliorate the potential risks cannabis can have on CF. Given limited evidence regarding the benefits of cannabis and the significant risks associated with cannabis use, clinicians have the responsibility to identify risk of cannabis use early, counsel patients about the risks of cannabis, provide a safe space for ongoing conversations about cannabis use in the context of CF care, and deliver evidence-based interventions to manage cannabis use among adolescents with comorbid CF. This article is protected by copyright. All rights reserved.

PMID:36349504 | DOI:10.1002/ppul.26241

Pediatr Pulmonol. 2022 Nov 8. doi: 10.1002/ppul.26239. Online ahead of print.

ABSTRACT

In past years, cystic fibrosis (CF) used to be considered a fatal disease of childhood. With early diagnosis and the advent of novel therapies, most patients survive to adulthood This article is protected by copyright. All rights reserved.

PMID:36349437 | DOI:10.1002/ppul.26239

Pediatr Pulmonol. 2022 Nov 8. doi: 10.1002/ppul.26233. Online ahead of print.

ABSTRACT

Immunoglobulin A (IgA) vasculitis or Henoch-Schönlein purpura (HSP) is the most common vasculitis of childhood. This article is protected by copyright. All rights reserved.

PMID:36349411 | DOI:10.1002/ppul.26233

BMC Bioinformatics. 2022 Nov 8;23(1):468. doi: 10.1186/s12859-022-05027-9.

ABSTRACT

BACKGROUND: Studying the co-occurrence network structure of microbial samples is one of the critical approaches to understanding the perplexing and delicate relationship between the microbe, host, and diseases. It is also critical to develop a tool for investigating co-occurrence networks and differential abundance analyses to reveal the disease-related taxa-taxa relationship. In addition, it is also necessary to tighten the co-occurrence network into smaller modules to increase the ability for functional annotation and interpretability of these taxa-taxa relationships. Also, it is critical to retain the phylogenetic relationship among the taxa to identify differential abundance patterns, which can be used to resolve contradicting functions reported by different studies.

RESULTS: In this article, we present Correlation and Consensus-based Cross-taxonomy Network Analysis (C3NA), a user-friendly R package for investigating compositional microbial sequencing data to identify and compare co-occurrence patterns across different taxonomic levels. C3NA contains two interactive graphic user interfaces (Shiny applications), one of them dedicated to the comparison between two diagnoses, e.g., disease versus control. We used C3NA to analyze two well-studied diseases, colorectal cancer, and Crohn's disease. We discovered clusters of study and disease-dependent taxa that overlap with known functional taxa studied by other discovery studies and differential abundance analyses.

CONCLUSION: C3NA offers a new microbial data analyses pipeline for refined and enriched taxa-taxa co-occurrence network analyses, and the usability was further expanded via the built-in Shiny applications for interactive investigation.

PMID:36348267 | DOI:10.1186/s12859-022-05027-9

Acta Pharmacol Sin. 2022 Nov 8. doi: 10.1038/s41401-022-00997-1. Online ahead of print.

ABSTRACT

Previous studies have shown mitochondrial dysfunction in various acute kidney injuries and chronic kidney diseases. Lipoic acid exerts potent effects on oxidant stress and modulation of mitochondrial function in damaged organ. In this study we investigated whether alpha lipoamide (ALM), a derivative of lipoic acid, exerted a renal protective effect in a type 2 diabetes mellitus mouse model. 9-week-old db/db mice were treated with ALM (50 mg·kg-1·d-1, i.g) for 8 weeks. We showed that ALM administration did not affect blood glucose levels in db/db mice, but restored renal function and significantly improved fibrosis of kidneys. We demonstrated that ALM administration significantly ameliorated mitochondrial dysfunction and tubulointerstitial fibrotic lesions, along with increased expression of CDX2 and CFTR and decreased expression of β-catenin and Snail in kidneys of db/db mice. Similar protective effects were observed in rat renal tubular epithelial cell line NRK-52E cultured in high-glucose medium following treatment with ALM (200 μM). The protective mechanisms of ALM in diabetic kidney disease (DKD) were further explored: Autodock Vina software predicted that ALM could activate RXRα protein by forming stable hydrogen bonds. PROMO Database predicted that RXRα could bind the promoter sequences of CDX2 gene. Knockdown of RXRα expression in NRK-52E cells under normal glucose condition suppressed CDX2 expression and promoted phenotypic changes in renal tubular epithelial cells. However, RXRα overexpression increased CDX2 expression which in turn inhibited high glucose-mediated renal tubular epithelial cell injury. Therefore, we reveal the protective effect of ALM on DKD and its possible potential targets: ALM ameliorates mitochondrial dysfunction and regulates the CDX2/CFTR/β-catenin signaling axis through upregulation and activation of RXRα. Schematic figure illustrating that ALM alleviates diabetic kidney disease by improving mitochondrial function and upregulation and activation of RXRα, which in turn upregulated CDX2 to exert an inhibitory effect on β-catenin activation and nuclear translocation. RTEC renal tubular epithelial cell. ROS Reactive oxygen species. RXRα Retinoid X receptor-α. Mfn1 Mitofusin 1. Drp1 dynamic-related protein 1. MDA malondialdehyde. 4-HNE 4-hydroxynonenal. T-SOD Total-superoxide dismutase. CDX2 Caudal-type homeobox transcription factor 2. CFTR Cystic fibrosis transmembrane conductance regulator. EMT epithelial mesenchymal transition. α-SMA Alpha-smooth muscle actin. ECM extracellular matrix. DKD diabetic kidney disease. Schematic figure was drawn by Figdraw ( www.figdraw.com ).

PMID:36347997 | DOI:10.1038/s41401-022-00997-1

Endocrinol Diabetes Nutr (Engl Ed). 2022 Nov 5:S2530-0180(22)00150-0. doi: 10.1016/j.endien.2021.08.009. Online ahead of print.

ABSTRACT

INTRODUCTION: Development of cystic fibrosis-related diabetes (CFRD) is associated with worsening of nutritional status and lung function, as well as increased mortality. The relevance of diagnosing the «pre-diabetic» status in these patients has not been addressed and the utility of HbA1c measurement in these patients is under discussion.

AIM: To study and characterise the different categories of carbohydrate metabolism impairment in paediatric patients with cystic fibrosis.

PATIENTS AND METHODS: A transversal study for characterisation of carbohydrate metabolism impairment according to clinical and anthropometric status and genetic background in 50 paediatric patients with cystic fibrosis (CF) was undertaken. Oral glucose tolerance tests (OGTT) for determination of glucose and insulin levels measurement and continuous subcutaneous glucose monitoring (CSGM) were performed.

RESULTS: 6% of patients presented with CFRD, 26% impaired glucose tolerance, 10% an indeterminate glucose alteration and 2% impaired fasting glucose. The severity of glycaemic impairment correlated positively with age and negatively with standardised height (p < 0.05) with intergroup differences in HbA1c levels (p < 0.01), with the latter correlating with the duration of hyperglycaemia throughout CSGM. No intergroup differences in mutation prevalence, pulmonary function test, nutritional status or disease exacerbations in the previous year were found. The daily enzyme replacement dose correlated with the glucose area under the curve (AUC, p < 0.05) but not with insulin-AUC.

CONCLUSIONS: An older age and greater enzyme replacement need are correlated with more severe carbohydrate metabolism impairment and lower standardized height in paediatric CF patients, with HbA1c correlating with the duration of hyperglycaemia. The study of the full glucose/insulin AUCs throughout the OGTT affords no additional information compared to glucose determination at 120 min in these patients.

PMID:36347795 | DOI:10.1016/j.endien.2021.08.009

J Cyst Fibros. 2022 Nov 5:S1569-1993(22)01391-1. doi: 10.1016/j.jcf.2022.10.009. Online ahead of print.

ABSTRACT

BACKGROUND: Nontuberculous mycobacteria (NTM) are opportunistic, difficult to treat pathogens. With increasing prevalence of NTM infections in people with cystic fibrosis (pwCF) and the improved life expectancy, the burden is expected to grow.

METHODS: We assessed the epidemiology and management of NTM isolation and disease in pwCF in the Netherlands using a survey and retrospective, case-controlled data from the Dutch CF Registry. We determined the isolation prevalence, treatment and outcomes from 2013-2019.

RESULTS: NTM isolation prevalence increased from 1.0% to 3.6% (2013-2019). This was a single NTM isolation in 53.7% of the adults and 60.0% of the children. M. abscessus and M. avium complex (MAC) were most frequent (47.1 and 30.9%). Of the treated pwCF, 48.5% attained culture conversion of M. abscessus; 54.5% for MAC. Children with an NTM isolation showed more infections with S. maltophilia and/or A. fumigatus (p < 0.001) compared to controls. In the year prior to NTM isolation, children in the NTM group had a lower mean FEV1% predicted (81.5 ± 16.7 vs. 88.6 ± 15.3, p = 0.024), while adults in the NTM group had more IV antibiotic days compared to controls (60 vs. 17, p = 0.047). In the following years, FEV1% predicted declined faster in pwCF with NTM than the control group (children: -3.8% vs. -1.6%, p = 0.023; adults: -0.7% and 0.4%, ns).

CONCLUSIONS: The isolation prevalence of 3.6%, poor treatment outcomes and associated lung function decline emphasize that NTM pulmonary disease (NTM-PD) is a significant health issue among pwCF in the Netherlands. Its prevention and treatment require increased attention.

PMID:36347785 | DOI:10.1016/j.jcf.2022.10.009

Contemp Clin Trials. 2022 Nov 5:106995. doi: 10.1016/j.cct.2022.106995. Online ahead of print.

ABSTRACT

It is important that patient-facing clinical trial information is easily understood by potential trial participants, trial participants, family members, friends and carers. The readability of a document refers to its typographic and linguistic characteristics that allow the text to be read and comprehended and it is recommended that healthcare providers aim that all information disseminated to the lay public be at a suitable readability level. Whilst there are established readability calculators for literature, there is no standard for health information. Several readability calculators are available that aids in the analyses of a text.URL or website's readability, however, to date there has been no head-to-head comparison. Five readability calculators were compared, including four online realtime calculators, (i) Readable (www.readable.com), (ii) www.webfx.com, (iii) www.datayze.com and (iv) www.online-utility.org, as well as the PC-based analyzer Microsoft Word (Microsoft Corp., USA). Three categories of text information were analysed, including (i) children's fairy tales (n = 20) (ii) scientific reports (n = 20) from BBC News websites and (iii) scientific abstracts (n = 20). This study demonstrated that varying scores were obtained by using different readability calculators. Based on these data in combination with issues including availability and ease-of-use, we advocate the use of Readable or Microsoft Word software to aid in the preparation of patient-facing clinical trial information. Clinical trial networks should now consider the need for standardisation of readability calculators and provide guidance to stakeholders so that readability of materials may be improved in a standardised and uniform manner.

PMID:36347454 | DOI:10.1016/j.cct.2022.106995

BMC Pulm Med. 2022 Nov 7;22(1):401. doi: 10.1186/s12890-022-02202-9.

ABSTRACT

BACKGROUND: N-acetylcysteine (NAC), which is specifically involved in airway mucus clearance and antioxidation, is recommended by the treatment guideline for non-cystic fibrosis bronchiectasis (NCFB). However, there is little clinical evidence of its long-term efficacy concerning quality of life (QoL) and exacerbation in patients with NCFB. In addition, the influences of NAC on airway bacterial colonization, chronic inflammation and oxidative stress in NCFB are also unclear.

METHODS: NINCFB is a prospective, multicentre, double-blind, randomised, placebo-controlled trial that will recruit 119 patients with NCFB and randomly divide them into an NAC group (n = 79) and a control group (n = 40). Participants in the NAC group will receive 600 mg oral NAC twice daily for 52 weeks, while patients in the control group will receive 600 mg placebo twice daily for 52 weeks. The information at baseline will be collected once participants are enrolled. The primary endpoints are the changes in St George's Respiratory Questionnaire scores and the number of exacerbations in 52 weeks. The secondary endpoints are the 16S rRNA of sputum and the levels of inflammatory factors and oxidative stressors in sputum and serum. Other data related to radiography, lung function tests, number of oral and/or intravenous antibiotic therapies and adverse events (AEs) will also be analysed. Further subgroup analysis distinguished by the severity of disease, severity of lung function, airway bacterial colonization and exacerbation frequency will be performed.

DISCUSSION: The objective of this study is to determine the long-term efficacy of NAC on QoL and exacerbation of NCFB and to explore the effectiveness of NAC for antibiosis, anti-inflammation and antioxidation in NCFB. The study results will provide high-quality clinical proof for the revision and optimization of treatment guidelines and for expert consensus on NCFB treatment.

TRIAL REGISTRATION: The trial was registered on the Chinese Clinical Trial Register at April 11, 2020 ( chictr.org.cn , ChiCTR2000031817).

PMID:36344940 | DOI:10.1186/s12890-022-02202-9

Zhonghua Jie He He Hu Xi Za Zhi. 2022 Nov 12;45(11):1117-1120. doi: 10.3760/cma.j.cn112147-20220518-00424.

ABSTRACT

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive or X-linked biallelic mutations inherited disease, characterized by motile cilia dysfunction. Typical manifestations include bronchiectasis, secretory otitis media, sinusitis, situs inversus, and infertility. PCD often needs to be differentiated from cystic fibrosis (CF) because of similar clinical manifestations. In this paper, a juvenile female who presented with recurrent cough and expectoration with fever since early childhood, had a history of secretory otitis media and sinusitis, and had been considered for the diagnosis of CF. After the discovery of compound heterozygous mutations in PCD related pathogenic genes by gene sequencing, combined with the clinical manifestations and imaging characteristics, PCD was finally diagnosed.

PMID:36344229 | DOI:10.3760/cma.j.cn112147-20220518-00424

Clin Chest Med. 2022 Dec;43(4):xiii-xvi. doi: 10.1016/j.ccm.2022.07.003.

NO ABSTRACT

PMID:36344084 | DOI:10.1016/j.ccm.2022.07.003

Clin Chest Med. 2022 Dec;43(4):821-840. doi: 10.1016/j.ccm.2022.07.002.

ABSTRACT

Lung transplantation provides a treatment option for many individuals with advanced lung disease due to cystic fibrosis (CF). Since the first transplants for CF in the 1980s, survival has improved and the opportunity for transplant has expanded to include individuals who previously were not considered candidates for transplant. Criteria to be a transplant candidate vary significantly among transplant programs, highlighting that the engagement in more than one transplant program may be necessary. Individuals with highly resistant CF pathogens, malnutrition, osteoporosis, CF liver disease, and other comorbidities may be suitable candidates for lung transplant, or if needed, multi-organ transplant. The transplant process involves several phases, from discussion of prognosis and referral to a transplant center, to transplant evaluation, to listing, transplant surgery, and care after transplant. While the availability of highly effective CF transmembrane conductance regulator (CFTR) modulators for many individuals with CF has improved lung function and slowed progression to respiratory failure, early discussion regarding transplant as a treatment option and referral to a transplant program are critical to maximizing opportunity and optimizing patient and family experience. The decision to be evaluated for transplant and to list for transplant are distinct, and early referral may provide a treatment option that can be urgently executed if needed. Survival after transplant for CF is improving, to a median survival of approximately 10 years, and most transplant survivors enjoy significant improvement in quality of life.

PMID:36344083 | DOI:10.1016/j.ccm.2022.07.002

Clin Chest Med. 2022 Dec;43(4):811-820. doi: 10.1016/j.ccm.2022.06.015.

ABSTRACT

Family planning in cystic fibrosis (CF) is an increasingly important aspect of care, as improvements in care and outcomes lead to a rise in the number of pregnancies and parenthood in people with CF. This article highlights: (1) Health considerations for people with CF related to pregnancy, contraception, and parenthood. (2) Facets of reproductive planning, fertility, and preconception counseling. (3) Relationship-centered reproductive health discussions.

PMID:36344082 | DOI:10.1016/j.ccm.2022.06.015

Clin Chest Med. 2022 Dec;43(4):791-810. doi: 10.1016/j.ccm.2022.06.014.

ABSTRACT

This article is intended for use among all cystic fibrosis care team members. It covers common mental health concerns and their unique presentations in persons with cystic fibrosis (pwCF) in areas such as depression, anxiety, trauma, behavioral disorders emerging in childhood, sleep, problematic eating patterns, and the impact of substance use. Furthermore, the authors address ways to manage these mental health symptoms through risk assessment, psychological interventions, and/or psychotropic medications. Quick reference tables are provided for evidence-based psychological interventions and medications often used for mental health conditions in pwCF.

PMID:36344081 | DOI:10.1016/j.ccm.2022.06.014

Clin Chest Med. 2022 Dec;43(4):773-789. doi: 10.1016/j.ccm.2022.06.013.

ABSTRACT

Endocrine comorbidities have become increasingly important medical considerations as improving cystic fibrosis (CF) care increases life expectancy. Although the underlying pathophysiology of CF-related diabetes remains elusive, the use of novel technologies and therapeutics seeks to improve both CF-related outcomes and quality of life. Improvements in the overall health of those with CF have tempered concerns about pubertal delay and short stature; however, other comorbidities such as hypogonadism and bone disease are increasingly recognized. Following the introduction of highly effective modulator therapies there are many lessons to be learned about their long-term impact on endocrine comorbidities.

PMID:36344080 | DOI:10.1016/j.ccm.2022.06.013

Clin Chest Med. 2022 Dec;43(4):757-771. doi: 10.1016/j.ccm.2022.06.016.

ABSTRACT

The development of formal transition models emerged to reduce variability in care, including cystic fibrosis (CF) responsibility, independence, self-care, and education (RISE), which provides a standardized transition program, including knowledge assessments, self-management checklists, and milestones for people with CF. Despite these interventions, the current landscape of health care transition (HCT) remains suboptimal, and additional focused attention on HCT is necessary. Standardization of assessment tools to gauge the efficacy of transfer from pediatric to adult care is a high priority. Such tools should incorporate both clinical and patient-centered outcomes to provide a comprehensive picture of progress and deficiencies of the HCT process.

PMID:36344079 | DOI:10.1016/j.ccm.2022.06.016

Clin Chest Med. 2022 Dec;43(4):743-755. doi: 10.1016/j.ccm.2022.07.001.

ABSTRACT

Clinical complications of cystic fibrosis (CF) include a variety of gastrointestinal (GI) and hepatobiliary manifestations. Recent years have witnessed several advances in the understanding and management of these complications, in addition to opportunities for therapeutic innovations. Herein we review the current understanding of these disorders and also discuss the management of the GI and hepatobiliary complications experienced by persons with CF.

PMID:36344078 | DOI:10.1016/j.ccm.2022.07.001