Pediatr Pulmonol. 2024 Sep 2. doi: 10.1002/ppul.27235. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) patients have a limited life expectancy, but significant medical advances now highlight the need for successful transition programs from pediatric to adult care. The goal of this project was to introduce the transition program CF R.I.S.E (Responsibility. Independence. Self-care. Education.) to a CF center with limited resources at Marmara University (MU).

METHODS: The program was adapted and translated into Turkish with the CF Foundation's permission. A team of experts collaborated to develop educational materials for patients and families. After translation and implementation of the CF S.O.B.E program, 11 Knowledge Assessment Questionnaire (KQA) tests were administered online to the patients aged between 16 and 25 years to assess the lack of patient knowledge.

RESULTS: The CF R.I.S.E program was successfully implemented within 6 months. A pilot study showed positive feedback from randomly selected patients, indicating the program's effectiveness and understandability. The mean age of the patients was 19.4 ± 2.9 years, and 42 (52%) were female. The mean forced expiratory volume (FEV1pp) was 76.3 ± 23.2. Fourteen (17.3%) and 4 (4.9%) of the patients colonized with Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA), respectively. Fifteen (18.5%) were on modulator therapy. Eleven Knowledge Assessment Questionnaires (KAQ) surveys were administered to 81 patients. The percentage of correct responses to the KAQs ranged from 47.9% to 68.3%.

CONCLUSION: MU CF Center in Turkey implemented the CF S.O.B.E (Responsibility, Self-care, Independence, and Education in Turkish) program. The center aims to make the program a regular practice and expand collaboration with adult clinics. Future studies will assess its long-term impact and applicability in different health settings. The final goal is to disseminate the program's resources and promote structured transition practices across the country.

PMID:39221873 | DOI:10.1002/ppul.27235

Pediatr Pulmonol. 2024 Sep 2. doi: 10.1002/ppul.27215. Online ahead of print.

ABSTRACT

INTRODUCTION: Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are respiratory conditions requiring regular chest radiography (CXR) surveillance to monitor pulmonary disease. However, CXR is insensitive for lung disease in CF and PCD. Lung ultrasound (LU) is a radiation-free alternative showing good correlation with severity of lung disease in CF but has not been studied in PCD.

METHOD: Standardized, six-zone LU studies and CXR were performed on a convenience sample of children with PCD or CF during a single visit when well. LU studies were graded using the LU scoring system, while CXR studies received a modified Chrispin-Norman score. Scores were correlated with clinical outcomes.

RESULT: Data from 30 patients with PCD and 30 with CF (median age PCD 11.5 years, CF 9.1 years) with overall mild pulmonary disease (PCD median FEV1 90% predicted, CF FEV1 100%) were analyzed. LU abnormalities appear in 11/30 (36%) patients with PCD and 9/30 (30%) with CF. Sensitivity, specificity, positive predictive, and negative predictive values for abnormal LU compared to the gold standard of CXR are 42%, 61%, 42%, and 61% in PCD, and 44%, 81%, 50%, and 77% in CF, respectively. Correlation between LU and CXR scores are poor for both diseases (PCD r = -0.1288, p = 0.4977; CF r = 0.0343, p = 0.8571), and LU score does not correlate with clinical outcomes in PCD.

CONCLUSION: The correlation of LU findings with CXR surveillance studies is poor in patients with mild disease burdens from PCD or CF, and LU scores do not correlate with clinical outcomes in PCD.

PMID:39221856 | DOI:10.1002/ppul.27215

J Bone Miner Res. 2024 Sep 2:zjae139. doi: 10.1093/jbmr/zjae139. Online ahead of print.

ABSTRACT

BACKGROUND: Improved survival in people with cystic fibrosis (pwCF) presents new complexities of care, including CF-related bone disease, a common complication in older pwCF. The trajectory of bone loss with age in this population remains unclear. The objective of this study was to estimate the average rate of change in bone mineral density (BMD) in adults with CF.

METHODS: This retrospective study included adults with CF, aged 25-48 years, followed between January 2000 and December 2021. Subjects with at least one dual-energy X-ray absorptiometry (DXA) scan were included. Scans obtained post-transplantation, after the initiation of bisphosphonates or cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy were excluded. The primary outcome was BMD (g/cm2) at the lumbar spine (LS) and femoral neck (FN). A linear mixed-effects model with both random intercept and random slope terms was used to estimate the average annual change in BMD.

RESULTS: A total of 1502 DXA scans in 500 adults (average age 28.4y) were included. There was a statistically significant annual decline in BMD of -0.008 gm/cm2/year (95% CI -0.009, -0.007) at the FN and -0.006 gm/cm2/year (95% CI -0.007, -0.004) at the LS. Relative to BMD at age 25, there was a -18.8% decline at the FN by age 48 years and a -11% decline at the LS. Pancreatic insufficient (PI) subjects had a faster rate of decline in BMD compared to pancreatic sufficient (PS) subjects. After adjusting for markers of disease severity, the annual rate of decline remained significant.

CONCLUSIONS: Individuals with CF experience bone loss at an age when it is not anticipated, thereby entering early adulthood, where further bone loss is inevitable especially with the decrease in estrogen during menopause, with suboptimal BMD. As the CF population ages, it will become very important to consider interventions to maximize bone health.

PMID:39221749 | DOI:10.1093/jbmr/zjae139

J Clin Transl Sci. 2024 May 7;8(1):e94. doi: 10.1017/cts.2024.532. eCollection 2024.

ABSTRACT

INTRODUCTION: Patients with cystic fibrosis (CF) experience frequent episodes of acute decline in lung function called pulmonary exacerbations (PEx). An existing clinical and place-based precision medicine algorithm that accurately predicts PEx could include racial and ethnic biases in clinical and geospatial training data, leading to unintentional exacerbation of health inequities.

METHODS: We estimated receiver operating characteristic curves based on predictions from a nonstationary Gaussian stochastic process model for PEx within 3, 6, and 12 months among 26,392 individuals aged 6 years and above (2003-2017) from the US CF Foundation Patient Registry. We screened predictors to identify reasons for discriminatory model performance.

RESULTS: The precision medicine algorithm performed worse predicting a PEx among Black patients when compared with White patients or to patients of another race for all three prediction horizons. There was little to no difference in prediction accuracies among Hispanic and non-Hispanic patients for the same prediction horizons. Differences in F508del, smoking households, secondhand smoke exposure, primary and secondary road densities, distance and drive time to the CF center, and average number of clinical evaluations were key factors associated with race.

CONCLUSIONS: Racial differences in prediction accuracies from our PEx precision medicine algorithm exist. Misclassification of future PEx was attributable to several underlying factors that correspond to race: CF mutation, location where the patient lives, and clinical awareness. Associations of our proxies with race for CF-related health outcomes can lead to systemic racism in data collection and in prediction accuracies from precision medicine algorithms constructed from it.

PMID:39220818 | PMC:PMC11362628 | DOI:10.1017/cts.2024.532

Front Endocrinol (Lausanne). 2024 Aug 16;15:1362950. doi: 10.3389/fendo.2024.1362950. eCollection 2024.

ABSTRACT

OBJECTIVE: Associations between acromegaly and several respiratory diseases, such as obstructive lung disease or sleep apnea, have been suggested, but the relationship between bronchiectasis and acromegaly is unclear. We investigated whether acromegaly is related to the development of bronchiectasis.

MATERIALS AND METHODS: Using the Korean National Health Insurance System database between 2006 and 2016, we studied the relationship between acromegaly and bronchiectasis in patients with acromegaly (n=2593) and controls (1:5 age- and sex-matched subjects without acromegaly, n=12965) with a mean follow-up period of 8.9 years. Cox proportional hazards regression analysis was used to assess the risk of bronchiectasis in patients with acromegaly compared with controls after adjusting for age, sex, household income, place, type 2 diabetes, hypertension, and dyslipidemia.

RESULTS: The mean age of the participants was 47.65 years, and male subjects comprised 45.62% of the cohort. The incidence rate of bronchiectasis in patients with acromegaly was 3.64 per 1,000 person-years and was significantly higher than that in controls (2.47 per 1,000 person-years) (log-rank test p = 0.002). In multivariable Cox proportional hazards regression modeling, the risk of bronchiectasis was significantly higher in patients with acromegaly than that in controls (HR: 1.49; 95% CI: 1.15-1.94, p = 0.0025) after adjusting for age, sex, household income, place, type 2 diabetes, hypertension, and dyslipidemia.

CONCLUSIONS: Our results suggest that acromegaly may be associated with bronchiectasis.

PMID:39220366 | PMC:PMC11361995 | DOI:10.3389/fendo.2024.1362950

J Inflamm Res. 2024 Aug 28;17:5701-5709. doi: 10.2147/JIR.S465413. eCollection 2024.

ABSTRACT

BACKGROUND: Non-cystic fibrosis bronchiectasis is associated with airway pathogen colonization. We planned to investigate the inflammatory markers in patients with different airway pathogens and their correlation with disease severity.

METHODS: We enrolled patients aged between 20 and 75 from October 2021 to August 2022. All patients had sputum evaluation for bacterial and fungal cultures before enrollment, and were classified into four groups according to the culture results.

RESULTS: Forty-four patients with non-CF bronchiectasis and six controls were enrolled and categorized as follows: Group 1, no pathogens identified in sputum cultures (n = 14); Group 2, positive fungal culture results (n = 18); Group 3, positive P. aeruginosa culture results (n = 7); and Group 4, positive culture results for both fungi and P. aeruginosa (n = 5). Group 4 had significantly higher serum defensin α1, IL-6 and tissue inhibitors of MMP (TIMP)-1 levels than group 1 patients. The serum levels of IL-6 and TIMP-1 were positively correlated with the FACED score and negatively correlated with distance-saturation product.

CONCLUSION: Significantly higher levels of serum IL-6 and TIMP-1 were found in the patients who had concomitant fungal and P. aeruginosa colonization, and were closely related to clinical severity and may have important roles in disease monitoring.

PMID:39219819 | PMC:PMC11366244 | DOI:10.2147/JIR.S465413

Haematologica. 2024 Aug 29. doi: 10.3324/haematol.2024.285740. Online ahead of print.

ABSTRACT

Not available.

PMID:39219498 | DOI:10.3324/haematol.2024.285740

Magn Reson Med. 2024 Sep 1. doi: 10.1002/mrm.30277. Online ahead of print.

ABSTRACT

PURPOSE: To develop a robust 3D ultrashort-TE (UTE) protocol that can reproducibly provide high-quality images, assessed by the ability to yield clinically diagnostic images, and is suitable for clinical translation.

THEORY AND METHODS: Building on previous work, a UTE sampled with Fermat looped orthogonally encoded trajectories (FLORET) was chosen as a starting point due to its shorter, clinically reasonable scan times. Modifications to previous FLORET implementations included gradient waveform frequency limitations, a new trajectory ordering scheme, a balanced SSFP implementation, fast gradient spoiling, and full inline reconstruction. FLORET images were collected in phantoms and humans on multiple scanners and sites to demonstrate these improvements.

RESULTS: The updates to FLORET provided high-quality images in phantom, musculoskeletal, and pulmonary applications. The gradient waveform modifications and new trajectory ordering scheme significantly reduced visible artifacts. Fast spoiling reduced acquisition time by 20%-28%. Across the various scanners and sites, the inline image quality was consistent and of diagnostic quality. Total image acquisition plus reconstruction time was less than 4 min for musculoskeletal and pulmonary applications with reconstructions taking less than 1 min.

CONCLUSION: Recently developed improvements for the FLORET sequence have enabled robust, high-quality UTE acquisitions with short acquisition and reconstruction times. This enables clinical UTE imaging as demonstrated by the implementation of the sequence and acquisition on five MRI scanners, at three different sites, without the need for any additional system characterization or measurements.

PMID:39219306 | DOI:10.1002/mrm.30277

Biomaterials. 2024 Aug 20;313:122753. doi: 10.1016/j.biomaterials.2024.122753. Online ahead of print.

ABSTRACT

Non-viral nanoparticles (NPs) have seen heightened interest as a delivery method for a variety of clinically relevant nucleic acid cargoes in recent years. While much of the focus has been on lipid NPs, non-lipid NPs, including polymeric NPs, have the possibility of improved efficacy, safety, and targeting, especially to non-liver organs following systemic administration. A safe and effective systemic approach for intracellular delivery to the lungs could overcome limitations to intratracheal/intranasal delivery of NPs and improve clinical benefit for a range of diseases including cystic fibrosis. Here, engineered biodegradable poly (beta-amino ester) (PBAE) NPs are shown to facilitate efficient delivery of mRNA to primary human airway epithelial cells from both healthy donors and individuals with cystic fibrosis. Optimized NP formulations made with differentially endcapped PBAEs and systemically administered in vivo lead to high expression of mRNA within the lungs in BALB/c and C57 B/L mice without requiring a complex targeting ligand. High levels of mRNA-based gene editing were achieved in an Ai9 mouse model across bronchial, epithelial, and endothelial cell populations. No toxicity was observed either acutely or over time, including after multiple systemic administrations of the NPs. The non-lipid biodegradable PBAE NPs demonstrate high levels of transfection in both primary human airway epithelial cells and in vivo editing of lung cell types that are targets for numerous life-limiting diseases particularly single gene disorders such as cystic fibrosis and surfactant deficiencies.

PMID:39217793 | DOI:10.1016/j.biomaterials.2024.122753

J Cyst Fibros. 2024 Aug 29:S1569-1993(24)00831-2. doi: 10.1016/j.jcf.2024.08.005. Online ahead of print.

ABSTRACT

Glucagon-like-peptide-1 (GLP-1) agonists are commonly used to improve glycemic control and promote weight loss in individuals with type 2 diabetes mellitus (T2DM) and/or obesity. However, there is a paucity of evidence regarding GLP-1 agonist use in people with cystic fibrosis (pwCF). We present 11 people with CF (males: 3, females: 7; age range 24-47; BMI range 25.7-43.7) treated with GLP-1 agonists (semaglutide: 9,tirzepatide: 2) for variable duration (1-50 months). All experienced weight loss on GLP- 1 agonist therapy (median change in weight = -7.2 kg; change in BMI [kg/m2] = -0.9 to -8.1). Eight pwCF showed improvement in percent predicted forced expiratory volume in 1 second (ppFEV1) [change = -5 to + 18] and nine pwCF showed improvement in percent predicted forced vital capacity (ppFVC) [change= +1 to + 26]. Of the 7 pwCF with CFRD, all reduced their insulin quantity (mean, 31.5 % decrease in total daily insulin dose), and glucose time in range improved for most (mean, +11 % increase from baseline). Four pwCF stopped using GLP-1 agonists: 2 due to severe nausea/vomiting, 1 due to lack of perceived benefit, and 1 due to change in insurance coverage. This report is the largest published series to date of pwCF treated with GLP-1 agonist therapy. With the addition of GLP-1 agonists, all individuals experienced weight loss and a reduction in daily insulin dose, and most had improvement in pulmonary function. Future multi-center studies are needed to corroborate the efficacy and safety of these agents in the CF population.

PMID:39214747 | DOI:10.1016/j.jcf.2024.08.005

Aging (Albany NY). 2024 Aug 29;16. doi: 10.18632/aging.206093. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is characterized by chronic airway inflammation and premature aging. The link with leukocyte telomere length (LTL) as a marker of biological aging is unclear. We studied disease severity and LTL in 168 CF patients of which 85 patients had a second retrospective LTL assessment. A higher FEV1 was associated with longer LTL, with a stronger effect in men (5.08% longer LTL) compared to women (0.41% longer LTL). A higher FEV1/FVC ratio was associated with 7.05% (P=0.017) longer LTL in men. CF asthma, as defined by the treatment with inhaled corticosteroids, was associated with -6.65% shorter LTL (P=0.028). Men homozygous for the ΔF508 genotype showed a -10.48% (P=0.026) shorter LTL compared to heterozygotes. A genotype-specific non-linear association between LTL shortening and chronological age was observed. Stronger age-related LTL shortening was observed in patients homozygous for the ΔF508 genotype (P-interaction= 0.044). This work showed that disease severity in CF patients negatively influences LTL, with slightly more pronounced effects in men. The homozygous genotype for ΔF508 may play a role in LTL attrition in CF patients. Understanding factors in CF patients that accelerate biological aging provides insights into mechanisms that can extend the overall life quality in CF-diseased.

PMID:39213174 | DOI:10.18632/aging.206093

Toxicol Sci. 2024 Aug 30:kfae082. doi: 10.1093/toxsci/kfae082. Online ahead of print.

NO ABSTRACT

PMID:39212780 | DOI:10.1093/toxsci/kfae082

Pediatr Pulmonol. 2024 Aug 30. doi: 10.1002/ppul.27211. Online ahead of print.

ABSTRACT

INTRODUCTION: The triple combination of elexacaftor/tezacaftor/ivacaftor (ETI) has dramatically improved the outcome of people with Cystic Fibrosis (pwCF) with at least one F508del mutation. However, carriers of rare cystic fibrosis transmembrane conductance regulator (CFTR) variants are not candidates for this innovative treatment.

METHODS: In this observational study, we report the results of the compassionate use of ETI in 10 pwCF carriers of rare mutations after 2 months of treatment. Rectal organoids and short-term cultures of nasal epithelium obtained from rectal suction biopsies and nasal brushing were obtained from four subjects.

RESULTS: After 2 months of ETI, all patients (4 males, mean age 30.1 ± 13.3 years) showed a significant increase of FEV1% predicted values [+8.0 (3.5-12.7) %, p < 0.010], body mass index [+0.85 (0-1.22) kg/m2, p < 0.020] and cystic fibrosis questionnaire-revised [+19.5 (6.3-29.2) points, p < 0.009]. A significant decrease of sweat chloride concentration [-11.2 (-1.7 to -34.0) mmol/L, p < 0.020] and exacerbations [-1.5 (-2 to -1), p < 0.008] was also recorded. Overall, 7 out of 10 participants were considered full responders. All patients reported cough disappearance (n = 3) or reduction (n = 7). Long-term oxygen was discontinued in two out of three patients and one also stopped noninvasive ventilation and was removed from the lung transplantation waiting list.

CONCLUSIONS: Despite the limited number of cases, our results support the use of CFTR modulators in patients with rare CFTR variants that are not currently approved for ETI in Europe.

PMID:39212240 | DOI:10.1002/ppul.27211

Int Forum Allergy Rhinol. 2024 Aug 30. doi: 10.1002/alr.23439. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in cystic fibrosis (CF) by stabilizing the CFTR protein on respiratory epithelial surfaces. To determine the efficacy of CFTR modulators on sinonasal outcomes in patients with CF, we performed a meta-analysis of clinical trials to date that include functional and radiographic evidence of sinus disease.

METHODS: English full-text articles were searched in PubMed, Embase, and Scopus databases. Two reviewers screened articles and a third reviewer resolved disagreements. Articles were included if they reported functional or radiological sinonasal outcomes in patients with CF before and after CFTR modulator therapies. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and the risk of bias in non-randomized studies of interventions tool was used for quality assessment. The generic inverse variance method with random effects model was used for meta-analysis. Standardized mean difference (SMD) and mean difference (MD) were used as effect measurements.

RESULTS: Seven prospective and two retrospective studies representing 248 patients were included in this analysis. There was a significant improvement in sinonasal outcome test-22 scores on elexacaftor‒tezacaftor‒ivacaftor (MD = 12.80, [95% confidence interval, CI: 10.46‒15.13], p < 0.001, n = 222), with no heterogeneity detected (I2 = 0%, p = 0.820). There was also a significant improvement in Lund‒Mackay scores (SMD = 1.25, [95% CI: 0.58‒1.91], p < 0.001, n = 88), with heterogeneity detected (I2 = 67%, p = 0.030).

CONCLUSIONS: CFTR modulators improve functional and radiologic sinonasal outcomes. Given the utility of CFTR modulators, the treatment paradigm for CF-related chronic rhinosinusitis promises to evolve.

PMID:39212072 | DOI:10.1002/alr.23439

Int Forum Allergy Rhinol. 2024 Aug 30. doi: 10.1002/alr.23441. Online ahead of print.

ABSTRACT

Treatment of cystic fibrosis-related chronic rhinosinusitis should target sinonasal biofilms. NaHCO3 salts with/without xylitol have limited antibiofilm properties, whereas rhDNAse has not. Phage effectivity varies and depends on the phage and the combination with antibiotics.

PMID:39212056 | DOI:10.1002/alr.23441

Front Pediatr. 2024 Aug 15;12:1360227. doi: 10.3389/fped.2024.1360227. eCollection 2024.

ABSTRACT

INTRODUCTION: Sleep-disordered breathing (SDB) and gas exchange disorders are common in patients with cystic fibrosis (CF). Currently, the impact of the disease on sleep patterns in patients living at high altitude and the relationship of these patterns to lung function are largely unknown. The aim of this study was to determine the frequency of SDB in children with CF aged 6-18 years and the relationship between SDB and lung function (FEV1).

METHODS: This is an analytical cross-sectional study of children aged 6-18 years diagnosed with CF. Spirometry before and after bronchodilators and polysomnography with capnography were performed. Descriptive analysis of qualitative and continuous variables was performed. Spearman's correlation coefficient was used to determine the correlation between polysomnogram and lung function (FEV1).

RESULTS: Twenty-four patients with CF were included. The mean age was 10.5 ± 3.1 years and 62.5% were male. Nine children had bronchiectasis on chest CT. The median absolute baseline FEV1 was 1,880 (1,355-2,325) ml and 98% (83%-110%) of predicted value. No significant difference in FEV1% was observed between subjects with obstructive sleep apnea (OSA) and those without OSA (P = 0.56). The prevalence of OSA was 66.7% in children younger than 13 years and 40% in children older than 13 years. The Spearman correlation coefficient between FEV1 and percentage of total sleep time with saturation less than 90% (T90) was rho -0.52 (p-value = 0.018), and between FEV1 and percentage of total sleep time with saturation less than 85% (T85) was statistically significant with rho -0.45 (p-value = 0.041). A positive correlation was observed between FEV1 and SpO2 during sleep with rho 0.53 and a statistically significant p-value (0.014).

CONCLUSIONS: A high prevalence of sleep apnea was found in children with CF living at high altitude, with a negative correlation between FEV1 and T90 and T85 oxygenation indices, and a positive correlation between FEV1 and SpO2 during sleep.

PMID:39210986 | PMC:PMC11357949 | DOI:10.3389/fped.2024.1360227

EClinicalMedicine. 2024 Aug 2;75:102774. doi: 10.1016/j.eclinm.2024.102774. eCollection 2024 Sep.

ABSTRACT

BACKGROUND: Exocrine Pancreatic insufficiency (EPI) occurs following acute pancreatitis (AP) at variably reported rates and with unclear recovery timeline. The aim of this study was to establish the prevalence and predictors of EPI at 12 months after AP in a prospective cohort.

METHODS: In this prospective, multicentre, longitudinal cohort study, adult participants (≥18 years) admitted to the hospital with an AP attack (defined by Revised Atlanta Classification) were enrolled in a United States multi-centre longitudinal cohort (Sites: The Ohio State University, University of Pittsburgh, and Johns Hopkins University). Patients were excluded if they had pancreatic cancer, chronic pancreatitis, or malabsorptive disease (including previously diagnosed EPI). Participant data was obtained by interview and by review of the electronic medical record. EPI was assessed by stool fecal elastase (FE-1) levels collected at baseline, 3 months, and 12 months (primary endpoint). EPI was defined by FE-1 <200 μg/g; severe FE-1 level ≤100 μg/g; mild FE-1 101-200 μg/g. Multivariable logistic regression was used to identify predictors of EPI at 12 months. This study is registered with ClinicalTrials.gov, NCT03063398.

FINDINGS: EPI was observed in 29 (34.1%) of the 85 participants [44 (51.8%) male, mean age 54.7 ± 14.1 years] who provided stool samples at 12 months. For the study overall, participants were recruited between June 22, 2017 and October 18, 2021. A total of 5794 individuals were screened, 311 of whom were eligible for the study. 112 participants provided stool samples at baseline, 79 completed stool samples at 3 months, and 85 completed samples at 12 months. 64 participants included samples at all 3 timepoints. In univariable analysis, factors significantly associated with EPI at 12 months included recurrent (versus index) AP, pre-existing diabetes, alcohol, and idiopathic etiologies, and increasing severity of AP. In multivariable analysis, the odds of having EPI at 12 months increased 4-fold with idiopathic AP etiology (Odds Ratio 4.095, 95% Confidence Interval [CI] 1.418, 11.826), and 3-fold with moderately severe or severe AP (Odds Ratio 3.166, 95% CI 1.156, 8.670), and baseline diabetes mellitus (Odds Ratio 3.217, 95% CI 1.113, 9.298). Even individuals with an index mild attack of AP (n = 39) developed severe EPI at 12 months (prevalence 12.8%).

INTERPRETATION: EPI as diagnosed by FE-1 is present in over one third of prospectively assessed patients at 12 months post-AP. Since EPI develops in patients with mild AP, investigations are needed to understand the mechanisms of injury and identify methods for tailored screening.

FUNDING: This study was supported by an Investigator Initiated Research Grant from AbbVie, Inc.

PMID:39210941 | PMC:PMC11359981 | DOI:10.1016/j.eclinm.2024.102774

Pediatr Pulmonol. 2024 Aug 30. doi: 10.1002/ppul.27242. Online ahead of print.

NO ABSTRACT

PMID:39210831 | DOI:10.1002/ppul.27242

Clin Respir J. 2024 Sep;18(9):e70007. doi: 10.1111/crj.70007.

ABSTRACT

OBJECTIVE: Elexacaftor/tezacaftor/ivacaftor (E/T/I) has provided life-changing pharmacotherapy for many people with cystic fibrosis (CF), but conflicting literature exists regarding the effect on mental health. While some reports suggest E/T/I may induce adverse psychiatric symptoms, others report improvements in mental health symptoms. To add to this growing body of knowledge, we retrospectively analyzed depression and anxiety symptoms before and after E/T/I initiation in adults with CF at a single large US CF center.

METHOD: Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scores recorded in a database were studied. Patients with scores collected before and after E/T/I initiation were included. Regression analyses described associations between score changes and age, race, ethnicity, sex, CFTR variant, and prior depression and/or anxiety diagnoses. Secondary analyses examined possible confounding effects of the COVID-19 pandemic.

RESULTS: There was no change in mean GAD-7 (0.5 ± 5.3, p = 0.41) or PHQ-9 (-0.02 ± 6.0, p = 0.97) scores following initiation of E/T/I (N = 86). A trend between a prior diagnosis of depression and worsening in PHQ-9 post-E/T/I was observed (OR 3.58; p = 0.054).

CONCLUSIONS: Treatment with E/T/I does not lead to changes in depression or anxiety symptoms at the population level in this single center cohort study. A prior diagnosis of depression trended towards an increased odds of worsening PHQ-9 scores after E/T/I initiation.

PMID:39210645 | DOI:10.1111/crj.70007

Int J Mol Sci. 2024 Aug 14;25(16):8836. doi: 10.3390/ijms25168836.

ABSTRACT

Colorectal cancer (CRC) affects approximately 2 million people worldwide. Obesity is the major risk factor for CRC. In addition, obesity contributes to a chronic inflammatory stage that enhances tumor progression through the secretion of proinflammatory cytokines. In addition to an increased inflammatory response, obesity-associated cancer presents accrued molecular factors related to cancer characteristics, such as genome instability, sustained cell proliferation, telomere dysfunctions, angiogenesis, and microbial alteration, among others. Despite the evidence accumulated over the last few years, the treatments for obesity-associated CRC do not differ from the CRC treatments in normal-weight individuals. In this review, we summarize the current knowledge on obesity-associated cancer, including its epidemiology, risk factors, molecular factors, and current treatments. Finally, we enumerate possible new therapeutic targets that may improve the conditions of obese CRC patients. Obesity is key for the development of CRC, and treatments resulting in the reversal of obesity should be considered as a strategy for improving antineoplastic CRC therapies.

PMID:39201522 | PMC:PMC11354800 | DOI:10.3390/ijms25168836