Abdom Radiol (NY). 2024 Nov 11. doi: 10.1007/s00261-024-04636-7. Online ahead of print.

ABSTRACT

Cystic fibrosis is a common inherited autosomal recessive disease affecting 35,000 persons in the United States. It is caused by mutations of the cystic fibrosis transmembrane regulator (CFTR) gene, located on the long arm of chromosome 7.This protein carries chlorine in the membranes of epithelial cells of exocrine glands. Mutations in the CFTR gene results in production of abnormally viscous mucus. Although it primarily affects the lungs, cystic fibrosis is a multisystem disease with involvement of extra thoracic organs including the liver, pancreas, kidneys and digestive tract.With advances in the management of cystic fibrosis resulting in improved life expectancy, cystic fibrosis patients are surviving into adulthood and extrapulmonary disease has become more commonplace. It is essential that radiologists are aware of the spectrum of potential manifestations of cystic fibrosis to allow accurate diagnosis.The purpose of this manuscript is to provide an overview of the pathophysiology and imaging findings of abdominal entities unique to patients with cystic fibrosis. We will present a wide spectrum of renal, pancreatic, gastrointestinal, hepatobiliary and post-transplant cases describing the typical findings that will assist radiologists in providing a timely diagnosis for patients with cystic fibrosis.

PMID:39527257 | DOI:10.1007/s00261-024-04636-7

Methods Mol Biol. 2025;2864:281-297. doi: 10.1007/978-1-0716-4184-2_15.

ABSTRACT

Animal models can be helpful tools for deciphering the generation, maintenance, and role of tertiary lymphoid structures (TLS) during infections or tumor development. We describe here the establishment of a persistent lung infection in immune-competent mice by intratracheal instillation of agarose beads containing Pseudomonas aeruginosa or Staphylococcus aureus bacteria. After instillation, animals develop a chronic pulmonary infection, marked by the presence of TLS. This experimental setting allows the study of the function of TLS induced by bacteria encountered in patients with cystic fibrosis (CF) as P. aeruginosa and S. aureus are the two main bacterial strains that infect the bronchi of adult CF patients. Additionally, we describe also how to manipulate the immune response in these infected animals by targeting immune cells involved in TLS function. Overall, this approach makes it possible to explore the role of chronic inflammation in the induction and maintenance of TLS in infected tissues.

PMID:39527228 | DOI:10.1007/978-1-0716-4184-2_15

Pediatr Pulmonol. 2024 Nov 11:e27390. doi: 10.1002/ppul.27390. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is a multisystemic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, resulting in defective synthesis or function of the CFTR protein. Historically, CF treatment focused on managing symptoms and complications. Fortunately, modulator drugs are now available to directly target the defective CFTR protein. However, in some countries, such as Turkey, these drugs are not covered by social insurance. Consequently, many CF patients face barriers to accessing modulatory therapies or must interrupt their treatment. This study demonstrates the impact of interrupting modulator therapy on pulmonary function, emphasizing the need for uninterrupted continuous treatment.

METHODS: In this study, 39 CF patients receiving elexacaftor-tezacaftor-ivacaftor (ETI) at our clinic were retrospectively analyzed. Among the patients, 18 experienced one or more interruptions, ranging from 15 to 210 days during ETI treatment. We analyzed pulmonary function test results from 27 interruption periods.

RESULTS: At the beginning of the interruption, the mean percent predicted FEV1 (ppFEV1) was 69.59% ± 25.87%, which decreased to 64.96% ± 24.52% by the end of the interruption. There was a significant decrease with a mean change of 4.62 ± 8.49 (p = 0.008). However, no significant correlation was found between the interruption duration and FEV1 change.

CONCLUSION: Our results demonstrate that pulmonary functions are adversely affected by interruption periods, regardless of their duration. Even short interruptions have a significant impact on pulmonary functions. This underscores the need for uninterrupted continuation of modulatory treatment and for improved policies to ensure equitable access to treatment.

PMID:39526592 | DOI:10.1002/ppul.27390

Pediatr Pulmonol. 2024 Nov 11. doi: 10.1002/ppul.27402. Online ahead of print.

ABSTRACT

INTRODUCTION: Depression and anxiety are common in persons with cystic fibrosis (PwCF). Genetic polymorphisms in CYP2C19 and CYP2D6 are well-established predictors of selective serotonin reuptake inhibitors (SSRIs) treatment failure yet have not been studied specifically in PwCF. The purpose of this study was to determine the rate of SSRI failure in PwCF and to identify factors that predict treatment failure.

METHODS: A retrospective cohort study was conducted of PwCF prescribed an SSRI for depression or anxiety. Potential predictors of SSRI failure were compared between PwCF for SSRI treatment success and failure. When CYP2D6 and CYP2C19 pharmacogenetic (PGx) test results were available, SSRI selection was compared to appropriateness per Clinical PGx Implementation Consortium (CPIC) guideline. PGx results were not available at the time of prescribing.

RESULTS: The study included 184 PwCF and 45% experienced SSRI treatment failure. Demographics, concomitant drug-drug interactions, concomitant antidepressant medications, liver disease, and pulmonary function tests were not different between success and failure groups. Only 44 PwCF had PGx results and of these, only nine had actionable genotypes and prescribed an affected SSRI. This cohort had a failure rate of 78% (7 of 9) which was significantly higher compared to 40% (14 of 35) and 45% (83 of 184) in our PGx cohort and total cohort, respectively (p = 0.04; p = 0.04).

CONCLUSION: SSRI failure rate in PwCF is high and consistent with rates of the general population. Greater depression severity and number of SSRIs trialed were seen in the failure group. Pre-emptive PGx testing may improve SSRI success rates in PwCF.

PMID:39526586 | DOI:10.1002/ppul.27402

Pediatr Pulmonol. 2024 Nov 11. doi: 10.1002/ppul.27359. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is a progressive genetic disorder, with lung disease being the main cause of morbidity and mortality. While advances in treatment have extended life expectancy, lung function still declines over time. Early inflammation and chronic infection, particularly with pseudomonas, worsen outcomes. Current management focuses on nutrition, airway clearance and infection control, but CFTR modulators directly target the genetic defect, improving lung function and reducing pulmonary exacerbations. Early use of CFTR modulators can alter the course of the disease.

PMID:39526579 | DOI:10.1002/ppul.27359

Lancet Reg Health Eur. 2024 Oct 30;47:101117. doi: 10.1016/j.lanepe.2024.101117. eCollection 2024 Dec.

ABSTRACT

[This corrects the article DOI: 10.1016/j.lanepe.2024.100996.].

PMID:39526297 | PMC:PMC11550123 | DOI:10.1016/j.lanepe.2024.101117

eGastroenterology. 2024 Oct;2(3):e100098. doi: 10.1136/egastro-2024-100098.

ABSTRACT

Goblet cells (GCs) are specialised guardians lining the intestine. They play a critical role in gut defence and immune regulation. GCs continuously secrete mucus creating a physical barrier to protect from pathogens while harbouring symbiotic gut bacteria adapted to live within the mucus. GCs also form specialised GC-associated passages in a dynamic and regulated manner to deliver luminal antigens to immune cells, promoting gut tolerance and preventing inflammation. The composition of gut bacteria directly influences GC function, highlighting the intricate interplay between these components of a healthy gut. Indeed, imbalances in the gut microbiome can disrupt GC function, contributing to various gastrointestinal diseases like colorectal cancer, inflammatory bowel disease, cystic fibrosis, pathogen infections and liver diseases. This review explores the interplay between GCs and the immune system. We delve into the underlying mechanisms by which GC dysfunction contributes to the development and progression of gastrointestinal diseases. Finally, we examine current and potential treatments that target GCs and represent promising avenues for further investigation.

PMID:39524932 | PMC:PMC11542612 | DOI:10.1136/egastro-2024-100098

BMC Biol. 2024 Nov 11;22(1):256. doi: 10.1186/s12915-024-02056-z.

ABSTRACT

BACKGROUND: The interactions between bacterial pathogens and host cells are characterized by a multitude of complexities, leading to a wide range of heterogeneous outcomes. Despite extensive research, we still have a limited understanding of how bacterial motility in complex environments impacts their ability to tolerate antibiotics and adhere to mammalian cell surfaces. The challenge lies in unraveling the complexity of these interactions and developing quantitative microscopy approaches to predict the behavior of bacterial populations.

RESULTS: To address this challenge, we directed our efforts towards Pseudomonas aeruginosa, a pathogenic bacterium known for producing thick films in the lungs of cystic fibrosis patients, and Escherichia coli, used as a proof of concept to develop and demonstrate our single-cell tracking approaches. Our results revealed that P. aeruginosa exhibits diverse and complex interactions on mammalian cell surfaces, such as adhesion, rotational motion, and swimming, unlike the less interactive behavior of Escherichia coli. Our analysis indicated that P. aeruginosa demonstrated lower mean-squared displacement (MSD) values and greater adherence to mammalian cells compared to E. coli, which showed higher MSD slopes and less frequent adherence. Genetic mutations in membrane proteins of P. aeruginosa resulted in altered displacement patterns and reduced adhesion, with the ΔfliD mutant displaying a more Gaussian displacement distribution and significantly less adherence to mammalian cells. Adhesion and tolerance mechanisms are diverse and complex, potentially involving distinct pathways; however, our findings highlight the therapeutic potential of targeting the fliD gene (encoding a critical flagellum protein), as its deletion not only reduced adherence but also antibiotic tolerance.

CONCLUSIONS: Overall, our findings underscore the importance of single cell tracking in accurately assessing bacterial behavior over short time periods and highlight its significant potential in guiding effective intervention strategies.

PMID:39523331 | DOI:10.1186/s12915-024-02056-z

J Cyst Fibros. 2024 Nov 9:S1569-1993(24)01787-9. doi: 10.1016/j.jcf.2024.09.019. Online ahead of print.

ABSTRACT

Cystic fibrosis is a life-shortening genetic disease caused by pathological variants of the cystic fibrosis transmembrane conductance regulator gene. The CFTR modulator therapy elexacaftor, tezacaftor and ivacaftor (ETI) rescues CFTR protein function and has made a significant impact on the lives of many people with CF. In Europe, ETI is currently available for people with CF who have at least one F508del mutation whilst the effect of ETI on rare CFTR variants remains unknown, albeit that many of such variants may be restored through ETI. Italy has a high prevalence of rare CFTR variants compared to the rest of Europe, potentially leading to significant undertreatment of people with rare CFTR variants. In this study, we used patient-derived intestinal organoids to identify individuals harboring rare CFTR variants who might benefit from ETI modulator therapy. Two CFTR-dependent readouts (steady-state lumen area and forskolin-induced swelling) in intestinal organoids were characterized to assess CFTR function rescue upon ETI incubation. Functional restoration by CFTR modulators was compared to wild type CFTR function, ETI-treated organoids harboring genotypes currently eligible for ETI therapy (F508del/class I) and organoids harboring non-responsive genotypes. Our data showed in vitro response to ETI within or beyond the range of CFTR function associated with F508del-ETI in 19 out of 28 organoids. This suggest that a large percentage of people with rare CFTR variants without access to ETI may benefit from this treatment.

PMID:39523185 | DOI:10.1016/j.jcf.2024.09.019

J Clin Med. 2024 Oct 30;13(21):6530. doi: 10.3390/jcm13216530.

ABSTRACT

Pseudomonas aeruginosa (Pa) poses a significant threat to individuals with cystic fibrosis (CF), as this bacterium is highly adaptable and resistant to antibiotics. While early-stage Pa infections can often be eradicated with aggressive antibiotic therapy, chronic infections are nearly impossible to eliminate and require treatments that focus on long-term bacterial suppression. Without such suppression, these persistent infections can severely damage the lungs, leading to serious complications and a reduced life expectancy for CF patients. Evidence for a specific treatment regimen for managing Pa infections in CF patients remains limited. This narrative review provides a detailed analysis of antimicrobial therapies assessed in completed phase IV trials, focusing on their safety and efficacy, especially with prolonged use. Key antibiotics, including tobramycin, colistin, meropenem, aztreonam, ceftolozane/tazobactam, ciprofloxacin, and azithromycin, are discussed, emphasizing their use, side effects, and delivery methods. Inhaled antibiotics are preferred for their targeted action and minimal side effects, while systemic antibiotics offer potency but carry risks like nephrotoxicity. The review also explores emerging treatments, such as phage therapy and antibiofilm agents, which show promise in managing chronic infections. Nonetheless, further research is necessary to enhance the safety and effectiveness of existing therapies while investigating new approaches for better long-term outcomes.

PMID:39518670 | DOI:10.3390/jcm13216530

J Clin Med. 2024 Oct 25;13(21):6397. doi: 10.3390/jcm13216397.

ABSTRACT

Background/Objectives: Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are commonly used for allergic rhinitis (AR), yet limited research has directly compared their effects on quality of life (QoL). We aimed to assess QoL differences between SLIT and SCIT recipients. As both forms of immunotherapy have reported benefits, we hypothesize that patients undergoing SLIT and SCIT will have comparable QoL improvements. Methods: A cohort study included patients with AR treated with immunotherapy from 2018 to 2022. Patients with obstructive sleep apnea, primary ciliary dyskinesia, cystic fibrosis, vasculitis, rheumatoid arthritis, sarcoidosis, or lupus were excluded. QoL was evaluated using the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at multiple time points. Demographics, additional therapies, and allergen sensitivities were recorded. Data were analyzed using SPSS Statistics. Results: A total of 41 participants were eligible for inclusion. Both SLIT and SCIT groups exhibited reductions from baseline RQLQ scores. Within SLIT recipients, 5/7 RQLQ domains significantly improved. SCIT recipients showed significant QoL enhancement in 3/7 domains. The mean difference between SLIT and SCIT cohorts was -0.18 (p = 0.57, d = -0.18, 95% CI [-0.79, 0.43] at a mean treatment time of 18 months. Conclusions: SLIT and SCIT showed comparable RQLQ score reductions after 18 months of therapy, suggesting similar QoL benefits between the two treatment paradigms. Further investigation is needed to explore SLIT vs. SCIT differences in long-term QoL improvements beyond two years.

PMID:39518536 | DOI:10.3390/jcm13216397

J Clin Med. 2024 Oct 22;13(21):6309. doi: 10.3390/jcm13216309.

ABSTRACT

Background/Objective: Patients with severe asthma (SA) and non-cystic fibrosis bronchiectasis (BE) without microbiological colonization represent a unique and understudied population. Type 2-targeted biologic therapies have emerged as a promising treatment for these patients. However, predictive factors for achieving clinical remission remain unclear. This study aims to identify the predictive factors for achieving clinical remission in patients with severe asthma and non-colonized bronchiectasis undergoing type 2-targeted biologic therapies. Methods: A retrospective longitudinal analysis was conducted on 14 patients with severe asthma and non-cystic fibrosis bronchiectasis without microbiological colonization. Clinical remission was assessed at baseline (T0) and after 12 months (T1) of biologic therapy. Clinical remission was defined according to the Severe Asthma Network Italy (SANI) criteria, including the absence of oral corticosteroid use, no asthma-related symptoms, stable lung function, and no exacerbations. Logistic regression was performed to identify predictors of remission. ROC curves were constructed to evaluate the predictive accuracy of lung function parameters, specifically FEV1 and FVC. Results: After 12 months of biologic therapy, 28.6% of patients (n = 4) achieved clinical remission. The mean FEV1 percentage at baseline was significantly higher in the remission group (92.25 ± 15.64%) compared to the non-remission group (65.10 ± 23.36%, p = 0.034). Logistic regression analysis identified baseline FEV1 as a significant predictor of remission (OR = 1.008, p = 0.050). ROC curve analysis revealed that an FEV1 cutoff of 72.5% had a sensitivity of 100% and a specificity of 70% (AUC = 0.900, p = 0.024) for predicting clinical remission. Conclusions: FEV1 is a crucial predictor of clinical remission in patients with severe asthma and non-colonized bronchiectasis treated with type 2-targeted biologic therapies. An FEV1 threshold of 72.5% can guide clinicians in identifying patients most likely to achieve remission. These findings underline the importance of preserving lung function to optimize therapeutic outcomes in this complex population.

PMID:39518449 | DOI:10.3390/jcm13216309

Pediatr Res. 2024 Nov 8. doi: 10.1038/s41390-024-03689-0. Online ahead of print.

ABSTRACT

Newborn screening (NBS) in the United States began in the 1960s to detect inborn errors of metabolism that benefited from presymptomatic treatment compared with treatment after the development of symptoms and diagnosis. Over time, it expanded to include endocrinological disorders, hematological disorders, immunodeficiencies, and other treatable diseases such as lysosomal storage diseases (LSD), cystic fibrosis, X-linked adrenoleukodystrophy, and spinal muscular dystrophy. This expansion has been driven by new technologies (e.g., tandem mass spectrometry) and novel treatments (e.g., enzyme replacement therapy and stem cell transplant for LSDs). Advances in next-generation gene sequencing (NGS) enable rapid identification of many additional conditions that might benefit from early presymptomatic intervention. We review the NGS technologies that evolved as diagnostic testing and suggest issues to be resolved before their potential application to screening the asymptomatic population. We illustrate the importance of selecting diseases to be screened and propose recommendations to follow when variants of uncertain significance are found. We address ethical issues around achieving equity in the sensitivity of genomic NBS, access to follow-up and management, especially for people from diverse backgrounds, and other considerations. Finally, we discuss the potential benefits and harms of genomic NBS to the overall health of children with monogenic diseases. IMPACT: Genomic newborn screening programs are ongoing worldwide. Public discussion is needed as to whether genomic newborn screening should be offered as a public health program and, if so, what conditions should be screened for. Providers should understand that the sensitivity of genomic newborn screening is especially low for newborns from non-European populations. Methylation, large structural variants and repeat expansion variants are not amenable to next-generation sequencing-based genomic newborn screening. The article serves as a comprehensive guide to understanding issues that need to be solved before genomic newborn screening is implemented as a public health program.

PMID:39516573 | DOI:10.1038/s41390-024-03689-0

J Cyst Fibros. 2024 Nov 7:S1569-1993(24)01800-9. doi: 10.1016/j.jcf.2024.10.005. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic Fibrosis (CF) patients historically suffered from undernutrition, infection and inflammation. Insulin insufficiency-related protein catabolism further compromised health. We aimed to determine whether insulin improves protein catabolism in CF youth with abnormal glucose tolerance (AGT).

METHODS: This double-masked, placebo-controlled trial in CF youth age 10-25 with AGT who were in their usual state of health used triple-tracer stable-isotope methodology to measure protein turnover during a baseline test meal and after four weeks of insulin/placebo treatment. Healthy controls were assessed once. CF patients were randomized 1:1:1 to once-daily long-acting insulin (0.25 U/kg/d), three-times daily rapid-acting insulin (0.5 U/15gr carbohydrate), or injectable placebo.

RESULTS: Thirty CF patients completed the study. There were no differences in any measure of protein turnover between insulin- and placebo-treated subjects, including endogenous protein breakdown (primary study endpoint). In contrast to earlier studies, protein turnover in the 37 CF patients who completed the baseline meal was normal compared to 20 healthy controls. Meal isotope appeared in plasma earlier in CF than controls, suggesting more rapid gut emptying. The study was interrupted by the pandemic; futility analysis led to study discontinuation before the planned remaining 15 CF patients were studied.

CONCLUSIONS: Recent advances in CF have led to remarkable clinical improvements. In this study, CF youth with AGT had normal protein catabolism at baseline. Pre-meal or daily basal insulin therapy, while safe and well tolerated, did not significantly enhance protein turnover and does not appear to be necessary in clinically stable patients prior to development of CFRD.

PMID:39516143 | DOI:10.1016/j.jcf.2024.10.005

J Cyst Fibros. 2024 Nov 7:S1569-1993(24)01803-4. doi: 10.1016/j.jcf.2024.10.010. Online ahead of print.

ABSTRACT

BACKGROUND: Our study aimed to identify the social domains that pose the greatest barriers to managing and supporting pwCF, particularly in relation to income levels.

METHODS: To identify associations between income and health outcomes in pwCF in our center the shorter form of the survey "Your Current Life Situation" (YCLS) was used in face-to-face interviews. Participants were also asked to complete the validated Turkish versions of the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item Generalized Anxiety Disorder scale (GAD-7) to assess depression and anxiety, respectively.

RESULTS: In total, 282 pwCF were included in this study. 51.1 % were female (n = 144), mean (±SD) age was 13.8 (±8.7) years and 75 % (n = 211) were <18 years old. The median (IQR) values of pwCF; FEV1pp (percent predictive) 83 % (41-97), BMI (body mass index) 17 kg/m2 (15∼20), BMI z-score -0.1 (-1∼0.3). Of the pwCF in the study 89 % (n = 251) had an income below the poverty threshold and 21 % (n = 60) of them had an income below the hunger threshold. The results of YCLS survey showed that the highest level of insecurity was in the social domain (68.5 %, n = 193); this was followed by health and clinical care (62.1 %, n = 173), financial (37.9 %, n = 106), and food insecurity (37.2 %, n = 103). All individuals experiencing housing insecurity stated that they had requested help from local organisations.

CONCLUSION: The study highlights the substantial socioeconomic challenges faced by pwCF, a significant majority live below the poverty threshold and experience high levels of social and health insecurity, underscoring the need for comprehensive support systems to address these issues.

PMID:39516142 | DOI:10.1016/j.jcf.2024.10.010

Clin J Pain. 2024 Nov 1;40(11):665-672. doi: 10.1097/AJP.0000000000001237.

ABSTRACT

OBJECTIVE: Brain areas activated during pain can contribute to enhancing or reducing the pain experience, showing a potential connection between chronic pain and the neural response to pain in adolescents and youth.

METHODS: This study examined changes in brain activation associated with experiencing physical pain and observing physical and emotional pain in others by using functional magnetic resonance imaging (fMRI) before and after intensive interdisciplinary pain treatment (IIPT). Eighteen youths (age 14 to 18) with widespread chronic pain completed fMRI testing before and after IIPT to assess changes in brain activation in response to physical and emotional pain.

RESULTS: Broadly, brain activation changes were observed in frontal, somatosensory, and limbic regions. These changes may suggest improvements in descending pain modulation via thalamus and caudate, and the different pattern of brain activation after treatment suggests potentially better discrimination between physical and emotional pain. Brain activation changes were also correlated with improvements in clinical outcomes of catastrophizing (reduced activation in right caudate, right mid-cingulate, and postcentral gyrus) and pain-related disability (increased activation in precentral gyrus, left hippocampus, right middle occipital cortex, and left superior frontal gyrus).

DISCUSSION: These changes could indicate that reduced brain protective responses to pain were associated with treatment-related improvements. This pilot study highlights the need for larger trials designed to better understand the brain mechanisms involved in pediatric widespread pain treatment.

PMID:39514716 | DOI:10.1097/AJP.0000000000001237

Cardiovasc Diagn Ther. 2024 Oct 31;14(5):921-934. doi: 10.21037/cdt-24-167. Epub 2024 Oct 22.

ABSTRACT

The number of adults with congenital heart defects (ACHDs) is steadily increasing and is about 360,000 in Germany. Congenital heart defect (CHD) is often associated with pulmonary hypertension (PH), which sometimes develops early in untreated CHD. Despite timely treatment of CHD, PH not infrequently persists, redevelops in older age, and is associated with significant morbidity and mortality. The revised European Society of Cardiology (ESC)/European Respiratory Society (ERS) 2022 guidelines for the diagnosis and treatment of PH represent a significant contribution to the optimized care of those affected. However, the topic of "adults with congenital heart defects" is treated only relatively superficially in this context. After the first part commenting on a broad range of topics like definition, epidemiology, classification, diagnostics, genetics, risk stratification and follow-up, and gender aspects, the second part focuses on supportive therapy, special situations (pregnancy, contraception, non-cardiac surgery), targeted pharmacotherapy, organ transplantation, special management [shunt lesion, left ventricular (LV) disease, univentricular hearts], interventions, intensive care, ACHD follow-up, and future perspective. In the present article, therefore, this topic is commented on from the perspective of congenital cardiology. By examining these aspects in detail, this article aims to fill the gaps in the existing guidelines and provide a more thorough understanding from the perspective of congenital cardiology.

PMID:39513142 | PMC:PMC11538840 | DOI:10.21037/cdt-24-167

Cardiovasc Diagn Ther. 2024 Oct 31;14(5):935-948. doi: 10.21037/cdt-24-148. Epub 2024 Oct 22.

ABSTRACT

The number of adults with congenital heart defects (ACHDs) is steadily increasing and is about 360,000 in Germany. Congenital heart defect (CHD) is often associated with pulmonary hypertension (PH), which sometimes develops early in untreated CHD. Despite timely treatment of CHD, PH not infrequently persists, redevelops in older age, and is associated with significant morbidity and lethality. The revised European Society of Cardiology (ESC)/European Respiratory Society (ERS) 2022 guidelines for the diagnosis and treatment of PH represent a significant contribution to the optimized care of those affected. However, the topic of "adults with congenital heart defects" is treated only relatively superficially in this context. In the present article, part I, therefore, this topic is commented on in detail from the perspective of congenital cardiology with a special focus on definition, epidemiology, classification, diagnostics, genetics, risk stratification and follow-up and gender aspects of PH in ACHDs. This paper consists of two parts. Part II will provide comments on the topics of supportive therapy, special situations like pregnancy, contraception, and non-cardiac surgery, targeted pharmacotherapy, organ transplantation, special management like shunt lesion, left ventricular disease, and univentricular hearts, interventions, intensive care, ACHDs follow-up and future perspective on PH in ACHDs. By examining these aspects in detail, this article aims to fill the gaps in the existing guidelines and provide a more thorough understanding from the perspective of congenital cardiology.

PMID:39513141 | PMC:PMC11538847 | DOI:10.21037/cdt-24-148

Front Digit Health. 2024 Oct 24;6:1469860. doi: 10.3389/fdgth.2024.1469860. eCollection 2024.

ABSTRACT

BACKGROUND: Remote care usefulness and climate change co-benefits should be addressed simultaneously to incentivize political action.

OBJECTIVES: To assess the changes in healthcare consumption, lung function and greenhouse gas (GHG) emissions during the COVID-19 pandemic in Dutch cystic fibrosis (CF) care.

DESIGN: Retrospective multicentre observational study in five Dutch CF centres.

METHODS: Eighty-one participants were included. Healthcare consumption was described alongside the COVID-19 Stringency Index (2019-2022). Travel related GHG emissions were calculated for every clinic visit. Changes in percentage predicted Forced Expiratory Volume in one second (ppFEV1) were assessed using a paired-samples T-test.

RESULTS: Healthcare consumption patterns followed COVID-19 public health measure stringency but returned back to the "old normal". Emission of 5.450, 3 kg of carbon dioxide equivalents were avoided while quality of care was relatively preserved. ppFEV1 declined as expected (ΔMeans 3.69%, 95%CI 2.11-5.28).

CONCLUSION: Remote monitoring of lung function and symptoms and teleconsultations in CF can reduce GHG emissions while maintaining quality of care. As health sectors constitute a large share of national climate change footprints, digital health can partly alleviate this burden by reducing private travel.

PMID:39512858 | PMC:PMC11540799 | DOI:10.3389/fdgth.2024.1469860

Front Pharmacol. 2024 Oct 23;15:1461473. doi: 10.3389/fphar.2024.1461473. eCollection 2024.

ABSTRACT

INTRODUCTION: Respiratory diseases encompass a diverse range of conditions that significantly impact global morbidity and mortality. While common diseases like asthma and COPD exhibit moderate symptoms, less prevalent conditions such as pulmonary hypertension and cystic fibrosis profoundly affect quality of life and mortality. The prevalence of these diseases has surged by approximately 40% over the past 3 decades. Despite advancements in pharmacotherapy, challenges in drug administration, adherence, and adverse effects persist. This study aimed to develop and perform an interim validation of a Capacity-Motivation-Opportunity (CMO) model tailored for respiratory outpatients to enhance pharmaceutical care, which is the direct, responsible provision of medication-related care for the purpose of achieving definite outcomes that improve a patient's quality of life, and overall wellbeing.

METHODOLOGY: This cross-sectional, multicenter study was conducted from March 2022 to March 2023. It comprised four phases: 1) forming an expert panel of 15 hospital pharmacists, 2) selecting respiratory pathologies based on prevalence and severity, 3) developing the CMO model's pillars, and 4) integrating and conducting an interim validation of the model. The Capacity pillar focused on patient stratification and personalized care; the Motivation pillar aligned therapeutic goals through motivational interviewing; and the Opportunity pillar promoted the use of information and communication technologies (ICTs) for telemedicine.

RESULTS: The model included eight respiratory diseases based on expert assessment. For the Capacity pillar, 22 variables were defined for patient stratification, leading to three priority levels for personalized pharmaceutical care. In a preliminary test involving 201 patients across six hospitals, the stratification tool effectively classified patients according to their needs. The Motivation pillar adapted motivational interviewing techniques to support patient adherence and behavior change. The Opportunity pillar established teleconsultation protocols and ICT tools to enhance patient monitoring and care coordination.

CONCLUSION: The CMO model, tailored for respiratory patients, provides a comprehensive framework for improving pharmaceutical care. By focusing on patient-centered care, aligning therapeutic goals, and leveraging technology, this model addresses the multifaceted needs of individuals with respiratory conditions. Future studies are necessary to validate this model in other healthcare systems and ensure its broad applicability.

PMID:39512818 | PMC:PMC11540901 | DOI:10.3389/fphar.2024.1461473