JCI Insight. 2023 Jan 5:e161961. doi: 10.1172/jci.insight.161961. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is characterized by chronic bacterial infections leading to progressive bronchiectasis and respiratory failure. Pseudomonas aeruginosa (Pa) is the predominant opportunistic pathogen infecting the CF airways. The guanine nucleotide exchange factor Vav3 plays a critical role in Pa adhesion to the CF airways by inducing luminal fibronectin deposition that favors bacteria trapping. Here we report that Vav3 overexpression in CF is caused by upregulation of the mRNA-stabilizing protein HuR. We found that HuR accumulates in the cytoplasm of CF airway epithelial cells, binds to and stabilizes Vav3 mRNA. Interestingly, disruption of HuR-Vav3 mRNA interaction improved the CF epithelial integrity, inhibited the formation of the fibronectin-made bacterial docking platforms and prevented Pa adhesion to the CF airway epithelium. These findings indicate that targeting HuR represents a promising anti-adhesive approach in CF to prevent initial stages of Pa infection in a context of emergence of multidrug resistant pathogens.

PMID:36602863 | DOI:10.1172/jci.insight.161961

J Clin Microbiol. 2023 Jan 5:e0155822. doi: 10.1128/jcm.01558-22. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is characterized by mutations of CFTR that lead to increased viscous secretions, bacterial colonization, and recurrent infections. Chronic Pseudomonas aeruginosa infection in persons with CF is associated with progressive and accelerated lung function decline despite aggressive antibiotic treatment. We report the management of respiratory infections in persons with CF with antibiotic therapy that was based on the recommendations of AtbFinder, a novel, rapid, culture-based diagnostic test system that employs a novel paradigm of antibiotic selection. AtbFinder mimics bacterial interactions with antibiotics at concentrations that can be achieved in affected tissues or organs and models conditions of interbacterial interactions within polymicrobial biofilms. This open-label, single-arm, investigator-initiated clinical study was designed to identify the efficacy of antibiotics selected using AtbFinder in persons with CF. Microbiological and clinical parameters were assessed following the change of antibiotic therapy to antibiotics selected with AtbFinder between January 2016 and December 2018 and retrospectively compared with clinical data collected between January 2013 and December 2015. We enrolled 35 persons with CF (33 with chronic P. aeruginosa colonization). Antibiotics selected using AtbFinder resulted in clearance of P. aeruginosa in 81.8% of subsequent cultures, decreased pulmonary exacerbations from 1.21 per patient per annum to 0, and an increase in predicted percent predicted forced expiratory volume in 1 s up to 28.4% from baseline. The number of systemic antibiotic courses used in patients after switching to the AtbFinder-selected therapy was reduced from 355 to 178. These findings describe the superiority of antibiotic regimens selected with AtbFinder compared with routine antimicrobial susceptibility testing.

PMID:36602344 | DOI:10.1128/jcm.01558-22

Saudi Pharm J. 2022 Dec;30(12):1736-1747. doi: 10.1016/j.jsps.2022.10.002. Epub 2022 Oct 8.

ABSTRACT

Cystic fibrosis (CF) is a genetic disease that affects the exocrine glands and is caused by cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations. Lung disease is the leading cause of morbidity in patients. Target-specific treatment of CF has been achieved using monoclonal antibodies (mAbs). The purpose of this article is to discuss the possibility of treating CF with mAbs through their significant target specificity. We searched electronic databases in Web of Science, PubMed, EMBASE, Scopus, and Google Scholar from 1984 to 2021. We discussed the critical role of targeted therapy in cystic fibrosis, as it will be more effective at suppressing the molecular networks. After conducting a critical review of the available literature, we concluded that it is critical to understand the fundamental molecular mechanisms underlying CF prior to incorporating biologics into the therapy regimen. Omalizumab, Mepolizumab, Benralizumab, Dupilumab and KB001-A have been successfully screened for asthma-complicated CF, and their efficacies have been well reported. Despite the availability of effective targeted biologics, treating CF has remained a difficult task, particularly when it comes to reduction of secondary inflammatory mediators. This review emphasizes the overall views on CF, the immunological mechanism of CF, and the prospective therapeutic use of mAbs as potential targeted biologics for enhancing the overall status of human health.

PMID:36601503 | PMC:PMC9805982 | DOI:10.1016/j.jsps.2022.10.002

J Asthma Allergy. 2022 Dec 29;15:1861-1875. doi: 10.2147/JAA.S389985. eCollection 2022.

ABSTRACT

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) primarily complicates the course of asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). Mortality data of ABPA and the difference in all-cause mortality between ABPA with and without COPD are not available.

OBJECTIVE: We investigated the difference in all-cause mortality between ABPA with and without COPD.

METHODS: A retrospective review was performed among patients with the diagnosis of ABPA at Peking University People's Hospital between January 2010 and March 2022. Logrank test was performed to investigate the difference between all-cause mortality for ABPA with and without COPD and Cox regression analysis was performed to investigate the independent risk factors for all-cause mortality in patients with ABPA.

RESULTS: Sixty-one patients with ABPA were enrolled in this study. The follow-up duration was 50.38 months (3-143 months). In the COPD group, 7 patients died (7/10), while in the non-COPD group, 4 patients died (4/51). The 1-year survival rates of ABPA with and without COPD were 60% and 97.8%, respectively. The 5-year survival rates of ABPA with and without COPD were 40% and 94%, respectively. The Cox regression analysis showed that higher C-reactive protein (CRP) (HR = 1.017, 95% CI 1.004-1.031, P = 0.013) and complicating COPD (HR = 8.525, 95% CI 1.827-39.773, P = 0.006) were independent risk factors associated with mortality in patients with ABPA.

CONCLUSION: The all-cause mortality for ABPA with COPD is higher than that for ABPA without COPD. Higher CRP and complicating COPD are independent risk factor for mortality in patients with ABPA.

PMID:36601290 | PMC:PMC9807121 | DOI:10.2147/JAA.S389985

Cureus. 2022 Nov 29;14(11):e32016. doi: 10.7759/cureus.32016. eCollection 2022 Nov.

ABSTRACT

Pyometra is an easily overlooked disease with nonspecific symptoms; however, a delayed diagnosis can lead to severe complications. An 80-year-old frail woman presented to our hospital with a chief complaint of persistent fever for 10 days. Her blood tests showed an elevated inflammatory response, and computed tomography showed a 10-cm cystic lesion in the pelvic floor compressing the bladder. A catheter was inserted from the vagina into the uterine cavity, resulting in pus drainage and pyometra diagnosis. A pus culture was subsequently performed, which detected Achromobacter xylosoxidans, a common cause of respiratory tract infections in cystic fibrosis and bloodstream infections, andγ-streptococcus. To the best of our knowledge, this is the first report of pyometra caused by Achromobacter xylosoxidans. The patient was treated with drainage and piperacillin-tazobactam administration. Pyometra is especially prevalent in older women with impaired activities of daily living and dementia. Although fever, lower abdominal pain, and increased discharge may occur, symptoms are often nonspecific, and half of such cases are asymptomatic. Furthermore, delayed diagnosis can lead to perforation of the uterus and consequent pan-peritonitis. Thus, the diagnosis of pyometra should be considered in older women presenting with unknown fever, and imaging studies and gynecological consultation should be requested promptly.

PMID:36600853 | PMC:PMC9798926 | DOI:10.7759/cureus.32016

Curr Protein Pept Sci. 2023 Jan 4. doi: 10.2174/1389203724666230104163924. Online ahead of print.

ABSTRACT

Protein aggregation or amyloid formation has generally been recognized as an outcome of protein misfolding before or during the onset of certain disease conditions such as Alzheimer's, Cataracts, Huntington's, Cystic fibrosis, Diabetes type II, etc. On the other hand, several organisms have evolved mechanisms to sequester their protein in amyloid-like conformation, and these aggregates play a crucial role in their biochemical functioning. In principle, under certain conditions, all the proteins have this property to form amyloid-like aggregates, which can be toxic or non-toxic. Recent evidence suggests that several amyloids or amyloid-like protein aggregates are derived from various food products, particularly those rich in protein. Many of them are reported to be toxic, raising serious health concerns regarding consuming these amyloid-forming food products. On the other hand, ageing significantly impacts gastrointestinal health, predisposing the senior population to be more susceptible to protein aggregation-related issues. The outcome will be determined by the interaction between food-derived protein aggregates and gastrointestinal proteases, pH change, gut microbiota, and intestinal epithelium integrity. The current review outlines the recent development in this area and a new perspective for designing safe protein-rich diets for healthy nutrition.

PMID:36600621 | DOI:10.2174/1389203724666230104163924

Eur J Hosp Pharm. 2022 Dec 20:ejhpharm-2022-003545. doi: 10.1136/ejhpharm-2022-003545. Online ahead of print.

ABSTRACT

OBJECTIVES: Sophisticated scientific methods have facilitated dose individualisation with substantial advancements in therapeutic drug monitoring (TDM) practice. It is unclear whether these methods have translated to the clinical setting. This study aimed to determine current TDM practice for tobramycin monitoring in cystic fibrosis (CF) centres in the USA and Canada, UK and Ireland, and Australia and New Zealand due to a high prevalence of CF.

METHODS: A web-based survey was developed and circulated via CF specialist groups within the targeted geographical regions. Themes included centre demographics, tobramycin usage, dosing and infusion practices, TDM practices, and blood sampling methods.

RESULTS: In total 77 responses were received from 75 different CF centres over the 3-month evaluation period (October 2019-January 2020). Respondents were from the USA and Canada (60%), Australia and New Zealand (25%), and the UK and Ireland (15%). Tobramycin was used in 97% of sites, with an international variation in practice across all survey aspects including dosing and infusion practice. TDM-based dose adjustment in the UK and Ireland was most commonly based only on trough sample collection for avoidance of toxicity, where use of computer programs for targeting both efficacy and toxicity endpoints were most common in Australia and New Zealand. The underlying pharmacokinetic basis of that program was not known by 33% of sites who utilised a computer program for tobramycin dose individualisation.

CONCLUSION: There remains substantial heterogeneity in tobramycin management worldwide. Despite two decades of research into TDM of tobramycin, there has been a slow uptake of new technologies and evolution of practice. An improved understanding of TDM processes is required for translation of evidence-based research into clinical practice. International guidelines require updating due to the advances in research to support confidence in the changes in clinical practice.

PMID:36600520 | DOI:10.1136/ejhpharm-2022-003545

Pediatr Pulmonol. 2023 Jan 4. doi: 10.1002/ppul.26306. Online ahead of print.

ABSTRACT

INTRODUCTION: Members of an integrated pharmacy team (pharmacists and pharmacy technicians) have roles that have been identified in the literature as part of the multi-disciplinary cystic fibrosis (CF) care team. One role that has not specifically addressed is the administration of routine and recommended immunizations to people with CF (PwCF). According to care guidelines, PwCF of all ages should be provided all age-appropriate and recommended immunizations. Pharmacists and pharmacy technicians can administer immunizations per state laws. The Primary Children's CF Center decided to implement a comprehensive pharmacy-driven immunization care process model to impact immunization rates.

METHODS: A 24-month retrospective analysis was conducted with pediatric (18 years) PwCF at the Primary Children's CF Center. The primary outcome measures were the percentage (%) of PwCF who received PPSV23, and/or HPV, and/or meningococcal conjugate vaccine (MCV) immunizations 1-year post care process model implementation (October 1, 2021 to September 30, 2022) as compared to baseline values. The secondary outcome measures are the total number of immunizations, the number of each immunization provided, and the financial impact of pharmacy-driven immunization care process model 1-year post implementation.

RESULTS: During the 1-year post care process model implementation (October 1, 2021, to September 30, 2022), a total of 523 immunizations were provided to 243 pediatric PwCF. The most frequent immunizations provided were PPSV23 (160/523, 31%) and Coronavirus Disease 2019 (COVID-19) (154/523, 29%). The baseline percentages of eligible PwCF of PPSV23, HPV, and MCV were 27% (58/217), 43% (32/74), and 24% (8/34), respectively. The 1-year post-implementation percentages of PPSV23, HPV, and MCV were 99% (217/218, p<0.00001), 91% (67/74, p<0.00001), and 97% (33/34, p<0.00001), respectively. For COVID-19 immunizations, 56% of eligible PwCF (181/321) have received their first dose. Of these 181 PwCF, 70% (126/181) have received at least one dose of their primary series or booster during the 1-year post implementation period. The rate of those PwCF who have received at least one dose of a COVID-19 immunization from the age of 6 months-4 years, 5-11 years, and 12-18 years, was 37% (30/82), 60% (78/129), and 66% (73/110), respectively. For the financial impact generated during the 1-year immunization care process model post implementation period, 404 non-VFC immunizations were given for an estimated profit of $11,930.

CONCLUSIONS: The implementation of a pharmacy-driven immunization care process model is a way for integrated pharmacy teams to evolve with the CF center care model and have a role expansion in the care provided to PwCF. This article is protected by copyright. All rights reserved.

PMID:36600452 | DOI:10.1002/ppul.26306

BMJ Open. 2022 Dec 9;12(12):e065401. doi: 10.1136/bmjopen-2022-065401.

ABSTRACT

INTRODUCTION: There has been renewed interest in the therapeutic use of bacteriophages (phages); however, standardised therapeutic protocols are lacking, and there is a paucity of rigorous clinical trial data assessing efficacy.

METHODS AND ANALYSIS: We propose an open-label, single-arm trial investigating a standardised treatment and monitoring protocol for phage therapy. Patients included will have exhausted other therapeutic options for control of their infection and phage therapy will be administered under Australia's Therapeutic Goods Administration Special Access Scheme. A phage product with high in vitro activity against the targeted pathogen(s) must be available in line with relevant regulatory requirements. We aim to recruit 50-100 patients over 5 years, from any public or private hospitals in Australia. The standardised protocol will specify clinical assessments and biological sampling at scheduled time points. The primary outcome is safety at day 29, assessed by the frequency of adverse events, and overseen by an independent Data Safety Monitoring Board. Secondary outcomes include long-term safety (frequency of adverse events until at least 6 months following phage therapy), and feasibility, measured as the proportion of participants with>80% of minimum data available for analysis. Additional endpoints assessed include clinical response, patient/guardian reported quality of life measures, phage pharmacokinetics, human host immune responses and microbiome analysis. All trial outcomes will be summarised and presented using standard descriptive statistics.

ETHICS AND DISSEMINATION: Participant inclusion will be dependent on obtaining written informed consent from the patient or guardian. The trial protocol was approved by the Sydney Children's Hospitals Network Human Research Ethics Committee in December 2021 (Reference 2021/ETH11861). In addition to publication in a peer-reviewed scientific journal, a lay summary of study outcomes will be made available for participants and the public on the Phage Australia website (https://www.phageaustralia.org/).

TRIAL REGISTRATION NUMBER: Registered on ANZCTR, 10 November 2021 (ACTRN12621001526864; WHO Universal Trial Number: U1111-1269-6000).

PMID:36600337 | DOI:10.1136/bmjopen-2022-065401

BMC Microbiol. 2023 Jan 5;23(1):2. doi: 10.1186/s12866-022-02738-0.

ABSTRACT

BACKGROUND: Burkholderia cenocepacia is an opportunistic pathogen that can cause acute and chronic infections in patients with weakened immune systems and in patients with cystic fibrosis. B. cenocepacia is resistant to many antibiotics making treatment challenging. Consequently, there is a critical need for alternative strategies to treat B. cenocepacia infections such as using bacteriophages and/or bacteriophages with subinhibitory doses of antibiotic called phage-antibiotic synergy.

RESULTS: We isolated a bacteriophage, KP1, from raw sewage that infects B. cenocepacia. Its morphological characteristics indicate it belongs in the family Siphoviridae, it has a 52 Kb ds DNA genome, and it has a narrow host range. We determined it rescued infections in Lemna minor (duckweed) and moderately reduced bacterial populations in our artificial sputum medium model.

CONCLUSION: These results suggest that KP1 phage alone in the duckweed model or in combination with antibiotics in the ASMDM model improves the efficacy of reducing B. cenocepacia populations.

PMID:36600213 | DOI:10.1186/s12866-022-02738-0

Dig Dis Sci. 2023 Jan 4. doi: 10.1007/s10620-022-07812-1. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Cystic Fibrosis (CF) is associated with gut dysbiosis, local and systemic inflammation, and impaired immune function. Gut microbiota dysbiosis results from changes in the complex gut milieu in response to CF transmembrane conductance regulator (CFTR) dysfunction, pancreatic malabsorption, diet, medications, and environmental influences. In several diseases, alteration of the gut microbiota influences local and systemic inflammation and disease outcomes. We conducted a systematic review of the gut microbiota in CF and explored factors influencing dysbiosis.

METHODS: An electronic search of three databases was conducted in January 2019, and re-run in June 2021. Human, animal, and in vitro studies were included. The primary outcome was differences in the gut microbiota between people with CF (pwCF) and healthy controls. Secondary outcomes included the relationship between the gut microbiota and other factors, including diet, medication, inflammation, and pulmonary function in pwCF.

RESULTS: Thirty-eight studies were identified. The literature confirmed the presence of CF-related gut dysbiosis, characterized by reduced diversity and several taxonomic changes. There was a relative increase of bacteria associated with a pro-inflammatory response coupled with a reduction of those considered anti-inflammatory. However, studies linking gut dysbiosis to systemic and lung inflammation were limited. Causes of gut dysbiosis were multifactorial, and findings were variable. Data on the impact of CFTR modulators on the gut microbiota were limited.

CONCLUSIONS: CF-related gut dysbiosis is evident in pwCF. Whether this influences local and systemic disease and is amenable to interventions with diet and drugs, such as CFTR modulators, requires further investigation.

PMID:36600119 | DOI:10.1007/s10620-022-07812-1

Thorax. 2023 Jan;78(1):85-87. doi: 10.1136/thoraxjnl-2022-218772. Epub 2022 Sep 7.

ABSTRACT

Lymphangioleiomyomatosis (LAM) is a rare lung disease of women, causing cystic remodelling of the lung and progressive respiratory failure. The cellular composition, microenvironment and cellular interactions within the LAM lesion remain unclear. To facilitate data sharing and collaborative LAM research, we performed an integrative analysis of single-cell data compiled from lung, uterus and kidney of patients with LAM from three research centres and developed an LAM Cell Atlas (LCA) Web-Portal. The LCA offers a variety of interactive options for investigators to search, visualise and reanalyse comprehensive single-cell multiomics data sets to reveal dysregulated genetic programmes at transcriptomic, epigenomic and cell-cell connectome levels.

PMID:36599466 | DOI:10.1136/thoraxjnl-2022-218772

Thorax. 2023 Jan;78(1):88-91. doi: 10.1136/thorax-2022-219213. Epub 2022 Sep 9.

ABSTRACT

Replacing traditional airway clearance therapy (tACT) with exercise (ExACT) in people with cystic fibrosis (pwCF) is a top research priority. A UK-based e-Delphi consensus was performed to inform the type(s), duration and intensity of ExACT. The expert panel comprised CF physiotherapists, doctors, pwCF and parents/partners. Exercise ACT was considered to be aerobic activity, of at least 20 min duration and intense enough to elicit deep breathing. Consensus was reached that assessment breaths, coughs and huffs should accompany exercise to remove loose secretions, with support for trials to investigate ExACT versus tACT during times of stable disease but not pulmonary exacerbations.

PMID:36599464 | DOI:10.1136/thorax-2022-219213

Cell. 2022 Dec 26:S0092-8674(22)01377-0. doi: 10.1016/j.cell.2022.11.001. Online ahead of print.

ABSTRACT

Aging is driven by hallmarks fulfilling the following three premises: (1) their age-associated manifestation, (2) the acceleration of aging by experimentally accentuating them, and (3) the opportunity to decelerate, stop, or reverse aging by therapeutic interventions on them. We propose the following twelve hallmarks of aging: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. These hallmarks are interconnected among each other, as well as to the recently proposed hallmarks of health, which include organizational features of spatial compartmentalization, maintenance of homeostasis, and adequate responses to stress.

PMID:36599349 | DOI:10.1016/j.cell.2022.11.001

J Pediatr Gastroenterol Nutr. 2023 Jan 4. doi: 10.1097/MPG.0000000000003700. Online ahead of print.

ABSTRACT

OBJECTIVES: Recently, a genetic risk for chronic pancreatitis (CP) was found to be conferred by pathogenic variants in the transient receptor potential cation channel, subfamily V, member 6 (TRPV6). Interestingly, 20-57% of patients with functionally defective TRPV6 variants have other susceptibility genes such as cationic trypsinogen (PRSS1), serine protease inhibitor Kazal type 1 (SPINK1), chymotrypsin C (CTRC), cystic fibrosis transmembrane conductance regulator (CFTR), and carboxypeptidase A1 (CPA1). In this study, we focused on pediatric patients with acute recurrent pancreatitis (ARP) or CP with at least one variant in these five genes and investigated the presence of coexisting TRPV6 mutations.

METHODS: Ninety Japanese pediatric patients (median age at first onset, 8.0 years) who had at least one variant of these five genes were enrolled in this study. DNA samples were extracted for analysis from peripheral blood leukocytes. Coding regions of TRPV6 were screened by Sanger sequencing.

RESULTS: Regardless of functional defects or non-defects in TRPV6 variants, 14 of the 90 patients (15.6%) were trans-heterozygous for TRPV6 variants [p.A18S (n=3), p.C197R (n=3), p.I223T (n=3), p.D324N (n=4), p.M418V (n=3), p.V540F (n=1), p.A606T (n=1), and p.M721T (n=3)] and the five susceptibility genes noted above. Of these variants, p.D324N, p.V540F, and p.A606T are associated with pancreatitis. Three patients had the ancestral haplotype [p.C197R + p.M418V + p.M721T].

CONCLUSIONS: Overall, four of 90 patients (4.4%) had the coexistence of clearly pathogenic TRPV6 variants with pancreatitis-associated variants. The cumulative accumulation of these genetic factors may contribute to the development of pancreatitis at a young age.

PMID:36599151 | DOI:10.1097/MPG.0000000000003700

Am J Respir Crit Care Med. 2023 Jan 4. doi: 10.1164/rccm.202210-1938LE. Online ahead of print.

NO ABSTRACT

PMID:36599047 | DOI:10.1164/rccm.202210-1938LE

Colorectal Dis. 2023 Jan 4. doi: 10.1111/codi.16472. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic Fibrosis (CF) is a hereditary, life-limiting, multi-system condition that results in chronic respiratory infections, pancreatic insufficiency and intestinal inflammation. Evidence indicates that CF patients develop colorectal cancer (CRC) earlier and more often than the general population. Intestinal dysbiosis resulting from genetics and CF treatment is a contributing factor. This systematic review aims to evaluate the literature to compare the microbiome of adult CF patients to non-CF patients and to assess if these changes correspond with known CRC microbiome alterations.

METHODS: A systematic review across five databases was performed according to PRISMA guidelines. Studies focusing on adult CF patients, using next generation sequencing and had appropriate non-CF controls were included. Two reviewers independently screened results and assessed study quality using the Newcastle-Ottawa scale.

RESULTS: The search generated 2757 results. 118 studies were retained after reviewing the title/abstract and full article review found five studies met the inclusion criteria. All studies consistently showed reduced microbial diversity in CF patients and unique clustering between CF and control cohorts. 34 genera and 27 species were differently expressed between CF and controls. The CF cohort had a reduced number of short-chain fatty acid (SCFA) producing bacteria and a higher abundance of bacteria associated with CRC compared to controls.

CONCLUSION: There was substantial heterogeneity across all the studies with regards to methodologies and reporting. However, all studies consistently found CF patients had reduced microbial diversity, fewer SCFA producing bacteria and increased CRC associated bacteria. Further prospective studies employing consistent multi-omics approaches is needed to improve our understanding of the CF gut microbiome and its involvement in early onset CRC.

SIGNIFICANCE STATEMENT: This is the first systematic review to assess adult CF colorectal microbiome changes. This study shows CF patients have reduced SCFA producing bacteria and increased CRC associated bacteria compared to non-CF patients and may help to explain the increased risk of CRC in the CF cohort.

PMID:36598333 | DOI:10.1111/codi.16472

Turk Arch Pediatr. 2023 Jan;58(1):89-97. doi: 10.5152/TurkArchPediatr.2022.22130.

ABSTRACT

OBJECTIVE: The prevalence of acute pancreatitis and acute recurrent pancreatitis in children has increased over the years, and there are limited data about imaging findings. This study aimed to reveal the imaging findings of acute pancreatitis and acute recurrent pancreatitis in children at a tertiary care hospital.

MATERIALS AND METHODS: The patients with acute pancreatitis and acute recurrent pancreatitis diagnosed between January 2007 and December 2018 were included. Demographic and clinical features, follow-up period, and interventions were noted. Imaging features were evaluated for pancreatic enlargement, peripancreatic fluid, and biliary ducts for initial examination and pancreas parenchymal necrosis, peripancreatic collection, walled-off necrosis, pseudocyst, parenchymal atrophy, and biliary ductal dilatation for follow-up.

RESULTS: The study included 74 patients with a mean age of 9 ± 4.9 years. The most common causes of acute pancreatitis and acute recurrent pancreatitis were biliary tract anomalies (n = 21), biliary ductal stones (n = 9), and cystic fibrosis (n = 8). Findings consistent with acute pancreatitis were determined by ultrasound in 40.5% (n = 30/74), whereas by magnetic resonance imaging in 60% (n = 39/65). Forty-one percent of the patients (n = 16) with positive magnetic resonance imaging findings did not show any findings on ultrasound. Acute recurrent pancreatitis was seen in 32 patients (43.2%). Follow-up imaging was performed in 55 patients (74.3%) between 2 months and 11 years. At follow-up, 8 patients had peripancreatic collections (6 walled-off necrosis and 2 pseudocysts).

CONCLUSION: Recognizing the imaging findings of acute pancreatitis and its complications is crucial. Magnetic resonance imaging should be preferred as a second option following ultrasound, with the advantages of biliary ductal system delineation and better characterization of complications.

PMID:36598217 | DOI:10.5152/TurkArchPediatr.2022.22130

Future Med Chem. 2023 Jan 4. doi: 10.4155/fmc-2022-0262. Online ahead of print.

NO ABSTRACT

PMID:36597845 | DOI:10.4155/fmc-2022-0262

Pediatr Radiol. 2023 Jan 4. doi: 10.1007/s00247-022-05574-6. Online ahead of print.

ABSTRACT

BACKGROUND: The Brody II score uses chest CT to guide therapeutic changes in children with cystic fibrosis; however, patients and providers are often reticent to undergo chest CT given concerns about radiation.

OBJECTIVE: We sought to determine the ability of a reduced-dose photon-counting detector (PCD) chest CT protocol to reproducibly display pulmonary disease severity using the Brody II score for children with cystic fibrosis (CF) scanned at radiation doses similar to those of a chest radiograph.

MATERIALS AND METHODS: Pediatric patients with CF underwent non-contrast reduced-dose chest PCD-CT. Volumetric inspiratory and expiratory scans were obtained without sedation or anesthesia. Three pediatric radiologists with Certificates of Added Qualification scored each scan on an ordinal scale and assigned a Brody II score to grade bronchiectasis, peribronchial thickening, parenchymal opacity, air trapping and mucus plugging. We report image-quality metrics using descriptive statistics. To calculate inter-rater agreement for Brody II scoring, we used the Krippendorff alpha and intraclass correlation coefficient (ICC).

RESULTS: Fifteen children with CF underwent reduced-dose PCD chest CT in both inspiration and expiration (mean age 8.9 years, range, 2.5-17.5 years; 4 girls). Mean volumetric CT dose index (CTDIvol) was 0.07 ± 0.03 mGy per scan. Mean effective dose was 0.12 ± 0.04 mSv for the total examination. All three readers graded spatial resolution and noise as interpretable on lung windows. The average Brody II score was 12.5 (range 4-19), with moderate inter-reader reliability (ICC of 0.61 [95% CI=0.27, 0.84]). Inter-rater reliability was moderate to substantial for bronchiectasis (0.52), peribronchial thickening (0.55), presence of opacity (0.62) and air trapping (0.70) and poor for mucus plugging (0.09).

CONCLUSION: Reduced-dose PCD-CT permits diagnostic image quality and reproducible identification of Brody II scoring imaging findings at radiation doses similar to those for chest radiography.

PMID:36596868 | DOI:10.1007/s00247-022-05574-6