J Clin Endocrinol Metab. 2025 Feb 20:dgaf099. doi: 10.1210/clinem/dgaf099. Online ahead of print.

ABSTRACT

BACKGROUND: Highly effective CFTR modulators, such as elexacaftor/tezacaftor/ivacaftor (ETI), herald a new era in therapeutic strategy of cystic fibrosis (CF). ETI impact on glucose tolerance remains controversial.

METHODS: All the participants underwent a baseline oral glucose tolerance test (OGTT) before ETI initiation (M0) and 12 months (M12), and at 24 months if possible. The cohort was stratified in two subgroups based on the baseline OGTT: normal glucose tolerance (NGT) and abnormal glucose tolerance (AGT) defined by impaired fasting glucose or impaired glucose tolerance or diabetes not requiring insulin treatment.

RESULTS: We included 106 adolescents with CF (age 14.1±1.5 years), 75 with NGT, 31 with AGT. The baseline characteristics of the two groups were similar except for a higher glucose level at 1 and 2-h OGTT in the AGT group. ETI induced an increase in BMIz-score and in Forced Expiratory Volume in 1 second (FEV1) (p<0.001). After 12 months, participants with NGT did not experience any change of 1-h and 2-h glucose. By contrast, those with AGT displayed a reduction of 2-h glucose at M12 (p=0.006). 15out of the 31 (48%) adolescents in the AGT group reversed to NGT but 9/75 (17%) in the NGT group progressed to AGT. 3 participants with CF related diabetes at baseline reversed to AGT. 1-hour glucose concentrations at or above 8.7 mmol/L (157mg/dL) during baseline OGTT had 80% sensitivity to identify those with AGT at 12 months (OR 1.51 [1.20, 1.92], p=0.001). 20 participants had a 24-month OGTT that confirmed preserved insulin secretion.

CONCLUSION: ETI may improve glucose tolerance in adolescents with CF by preserving insulin secretion. 1-hour glucose during the OGTT helps to detect risk for AGT after ETI treatment.

PMID:39977216 | DOI:10.1210/clinem/dgaf099

Microbiology (Reading). 2025 Feb;171(2). doi: 10.1099/mic.0.001536.

ABSTRACT

Obtaining sputum samples from people with cystic fibrosis (pwCF) for microbiology has become challenging due to the positive clinical effects of the cystic fibrosis transmembrane conductance regulator modulator therapy, elexacaftor-tezacaftor-ivacaftor (ETI). Although ETI improves lung function and reduces sputum production, recent data shows that bacterial pathogens persist, making continued monitoring of infection important. As an alternative to sputum sampling, this study developed a non-invasive technique called 'Cough Breath' (CB) to identify volatile organic compounds (VOCs) in exhaled breath condensate (EBC) and link them to cystic fibrosis (CF) bacterial pathogens using purge and trap GC-MS. The CB culturing approach was able to isolate pathogens from expectorated particulates simultaneously with EBC collection; however, culturing positivity was low, with 6% of samples collected (n=47) positive for either Pseudomonas aeruginosa or Staphylococcus aureus. From EBC, we identified VOCs matching those uniquely produced by P. aeruginosa (7), S. aureus (12), Achromobacter xylosoxidans (8) and Granulicatella adiacens (2); however, the overall detection rate was also low. Expanding to VOCs produced across multiple pathogens identified 30 frequently detected in the EBC of pwCF, including 2,3-pentanedione, propyl pyruvate, oxalic acid diallyl ester, methyl isobutyl ketone, methyl nitrate, 2-propenal, acetonitrile, acetoin and 2,3-butanedione. Comparing isolate volatilomes and EBC samples from the same pwCF enhanced detection rates with key VOCs, such as 2,3-pentanedione (86%) and propyl pyruvate (83%), in P. aeruginosa isolates. Further investigation showed that VOC production differed across strains and at different growth phases, creating variability that may explain the overall low EBC detection rate. Although this study successfully cultured CF pathogens from cough particulates and matched their unique VOCs in EBC samples, our results indicate that microbial volatiles more generally indicative of infection, such as 2,3-pentanedione, may have the most utility in aiding diagnostics in pwCF on ETI who have reduced sputum production in the clinic.

PMID:39976612 | DOI:10.1099/mic.0.001536

Eur J Gastroenterol Hepatol. 2025 Jan 21. doi: 10.1097/MEG.0000000000002917. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis-related liver disease (CFRLD) is a health problem that can affect as many as 30-40% of cystic fibrosis patients by the age of 12 years. We studied the epidemiology of CFRLD thanks to the first exclusively pediatric CFRLD patient registry to date.

METHODS: Descriptive cross-sectional study. Information from medical records from January 2018 to December 2020 is collected. CFRLD was classified according to the European Society of Paediatric Gastroenterology, Hepatology and Nutrition 2017 criteria.

RESULTS: Data were collected from 168 pediatric patients diagnosed with CFRLD (90.5% liver involvement without cirrhosis and 8.5% multinodular cirrhosis).

CONCLUSION: In this national registry, including exclusively pediatric population, liver disease is diagnosed around 7 years of age. Liver involvement without cirrhosis is the most frequent finding among our patients but about 9% of the patients already had cirrhosis. CFRLD is one of the challenges faced by pediatric gastroenterologists in the future and national registries give us the opportunity to further study and broaden our knowledge.

PMID:39976013 | DOI:10.1097/MEG.0000000000002917

bioRxiv [Preprint]. 2025 Feb 8:2025.02.03.636268. doi: 10.1101/2025.02.03.636268.

ABSTRACT

Constipation causes significant morbidity in Cystic Fibrosis (CF) patients. Using CF patient (F508del) derived ex vivo ileal and distal colonic/rectal enteroids as a model and the Forskolin Induced Swelling Assay (FIS), we compared CFTR mediated fluid secretion in human enterocytes across the crypt-villus axis. CFTR expression and FIS decreased as enterocytes differentiated from crypt to become partially differentiated and then mature villus cells . While there was no FIS response in undifferentiated (crypt enterocytes) F508del-CF enteroids, partially differentiated F508del-CF enteroids had a swelling response to forskolin (cAMP) and linaclotide (cGMP) which was ∼48%, and ∼67% of the response in healthy enteroids, respectively and was prevented by a CFTR inhibitor. Also, linaclotide and a general PDE inhibitor independently enhanced combined CFTR-modulator-induced FIS response from partially differentiated F508del-CF enteroids. These findings demonstrate that partially differentiated ileal and distal colonic F508del-CFTR enteroids can be stimulated to secrete fluid by cAMP and cGMP.

PMID:39975121 | PMC:PMC11838475 | DOI:10.1101/2025.02.03.636268

bioRxiv [Preprint]. 2025 Jan 27:2025.01.24.634747. doi: 10.1101/2025.01.24.634747.

ABSTRACT

Single-cell RNA sequencing (scRNA-seq) studies identified a novel subpopulation of epithelial cells along the rostrocaudal axis of human intestine specifically marked by bestrophin 4 (BEST4) that are enriched for genes regulating pH, GPCR acid-sensing receptors, satiety, cGMP signaling, HCO3 - secretion, ion transport, neuropeptides, and paracrine hormones. Interestingly, BEST4+ cells in the proximal small intestine express CFTR but have not been linked to the previously described CFTR High Expresser Cell (CHE) subpopulation in rat and human intestine. ScRNA-seq studies in rat jejunum identified CHEs and a gene expression profile consistent with human small intestinal BEST4+ and neuropod cells. Protein immunolocalization confirmed that CHEs express CFTR, BEST4, neuropod proteins, high levels of intracellular uroguanylin (UGN), guanylyl cyclase-C (GC-C), and the proton channel otopetrin 2 (OTOP2), and display long basal processes connecting to neurons. OTOP2, GC-C, and CFTR traffic robustly into the apical domain of CHEs in response to acidic luminal conditions, indicating their roles in luminal pH regulation. In the ΔF508 cystic fibrosis (CF) rat jejunum, the loss of apical CFTR did not affect BEST4 protein expression in CHEs. However, there was an increased abundance of CHE cells in the ΔF508 rat jejunum compared to wild-type animals. Furthermore, ΔF508 rat CHEs expressed higher levels of GC-C at the apical domain compared to wild-type. These data implicate CHEs in intestinal CF disease pathogenesis.

NEW & NOTEWORTHY: This is the first study to identify CFTR High Expresser cells in the rat small intestine as neuropod cells capable of sensing and responding to luminal pH. This study also provides the first characterization of CFTR and relevant mRNA and proteins in CHEs in CF rat models that provide insights into the significance of CHEs to CF intestinal disease.

PMID:39974899 | PMC:PMC11838207 | DOI:10.1101/2025.01.24.634747

Lancet Reg Health Eur. 2024 Sep 15;45:101061. doi: 10.1016/j.lanepe.2024.101061. eCollection 2024 Oct.

NO ABSTRACT

PMID:39974772 | PMC:PMC11838078 | DOI:10.1016/j.lanepe.2024.101061

FEBS Lett. 2025 Feb 20. doi: 10.1002/1873-3468.70013. Online ahead of print.

ABSTRACT

The arachidonic acid (AA) pathway promotes tumor progression by modulating the complex interactions between cancer and immune cells within the microenvironment. In this Review, we summarize the knowledge acquired thus far concerning the intricate mechanisms through which eicosanoids either promote or suppress the antitumor immune response. In addition, we will discuss the impact of eicosanoids on immune cells and how they affect responsiveness to immunotherapy, as well as potential strategies for manipulating the AA pathway to improve anticancer immunotherapy. Understanding the molecular pathways and mechanisms underlying the role played by AA and its metabolites in tumor progression may contribute to the development of more effective anticancer immunotherapies.

PMID:39973474 | DOI:10.1002/1873-3468.70013

Int Forum Allergy Rhinol. 2025 Feb 19. doi: 10.1002/alr.23549. Online ahead of print.

NO ABSTRACT

PMID:39972960 | DOI:10.1002/alr.23549

Nat Rev Cardiol. 2025 Feb 19. doi: 10.1038/s41569-025-01130-5. Online ahead of print.

ABSTRACT

Ageing of the cardiovascular system is associated with frailty and various life-threatening diseases. As global populations grow older, age-related conditions increasingly determine healthspan and lifespan. The circulatory system not only supplies nutrients and oxygen to all tissues of the human body and removes by-products but also builds the largest interorgan communication network, thereby serving as a gatekeeper for healthy ageing. Therefore, elucidating organ-specific and cell-specific ageing mechanisms that compromise circulatory system functions could have the potential to prevent or ameliorate age-related cardiovascular diseases. In support of this concept, emerging evidence suggests that targeting the circulatory system might restore organ function. In this Roadmap, we delve into the organ-specific and cell-specific mechanisms that underlie ageing-related changes in the cardiovascular system. We raise unanswered questions regarding the optimal design of clinical trials, in which markers of biological ageing in humans could be assessed. We provide guidance for the development of gerotherapeutics, which will rely on the technological progress of the diagnostic toolbox to measure residual risk in elderly individuals. A major challenge in the quest to discover interventions that delay age-related conditions in humans is to identify molecular switches that can delay the onset of ageing changes. To overcome this roadblock, future clinical trials need to provide evidence that gerotherapeutics directly affect one or several hallmarks of ageing in such a manner as to delay, prevent, alleviate or treat age-associated dysfunction and diseases.

PMID:39972009 | DOI:10.1038/s41569-025-01130-5

Curr Gastroenterol Rep. 2025 Feb 19;27(1):14. doi: 10.1007/s11894-025-00959-7.

ABSTRACT

PURPOSE OF REVIEW: Common indications to evaluate exocrine pancreatic function in children include chronic diarrhea, steatorrhea, failure to thrive, cystic fibrosis and those with chronic abdominal pain due to chronic pancreatitis where imaging studies are normal [1]. Exocrine Pancreatic Insufficiency (EPI) has a spectrum of severity. In children often remains an underdiagnosed condition, particularly in its mild, partial, and isolated enzyme deficiency forms. The purpose of this review is to help understand the different varieties of EPI including isolated pancreatic enzyme deficiencies as possible causes of malnutrition and growth failure in pediatric patients.

RECENT FINDINGS: Among the indirect diagnostic methods, the fecal elastase-1 (FE-1) testing is the most widely used one. While it has good sensitivity and specificity in severe pancreatic damage, like cystic fibrosis in children, its performance in the diagnosis of mild, partial, and isolated enzyme deficiencies is poor. Direct pancreatic function testing performed during endoscopy (ePFT), has emerged as a more sensitive and specific method for assessing all forms of exocrine pancreatic function. Notably, recent guidelines from the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) emphasize the importance of ePFT in pediatric patients. Most of the pediatric practitioners taught that the pancreas has only two diseases, cystic fibrosis and pancreatitis. They are missing the fact that pancreas, like other digestive organs, can have different, many times secondary, dysfunctions that influence the growth of children. Most pediatric gastroenterologists still use the fecal elastase-1 (FE-1) test, however, this lacks sufficient specificity and sensitivity [2-5] especially in patients with mild or early pancreatic disease or those with isolated enzyme deficiencies [5]. The most accurate diagnostic modality to explore these conditions is ePFT. In this review we highlighted the critical importance of direct pancreatic function testing. Enhancing clinical awareness and incorporating direct testing methods can ultimately improve outcomes for affected children.

PMID:39971805 | DOI:10.1007/s11894-025-00959-7

J Cyst Fibros. 2025 Feb 18:S1569-1993(25)00063-3. doi: 10.1016/j.jcf.2025.02.012. Online ahead of print.

ABSTRACT

The year 2024 marks a pivotal moment in the field of cystic fibrosis (CF) treatment, characterised by significant advancements in clinical care and an expanding body of literature on CF transmembrane conductance regulator (CFTR) modulators. These CFTR therapies have transformed the landscape of CF management, offered systemic benefits, and established new guidelines for assessing clinical manifestations and therapies. Additionally, progress has been made in newborn screening (NBS), diagnosis, and understanding outcomes for individuals with CF-related metabolic syndrome or inconclusive diagnostic results. However, amidst these clinical milestones, disparities in global access to CFTR modulators (CFTRm) persist, threatening to exacerbate existing inequities in CF care. This review provides a focused overview of the most impactful articles from 2024, highlighting both the clinical advancements and the pressing global accessibility challenges that define this transformative era in CF research and treatment.

PMID:39971692 | DOI:10.1016/j.jcf.2025.02.012

J Cyst Fibros. 2025 Feb 18:S1569-1993(25)00062-1. doi: 10.1016/j.jcf.2025.02.011. Online ahead of print.

ABSTRACT

BACKGROUND: AI-aided home stethoscopes offer the opportunity of continuous remote monitoring of cystic fibrosis (CF) patients, reducing the need for clinic visits.

AIM: This study aimed to analyze the possibility of detecting CF pulmonary exacerbations (PEx) at home using an AI-aided stethoscope (AIS).

MATERIALS AND METHODS: In a six-month study, 129 CF patients (85 children, 44 adults) used AIS for at least weekly self-examinations, recording various parameters: wheezes, rhonchi, crackles intensity, respiratory and heart rate, and inspiration-to-expiration ratio. Health state surveys were also completed. Physicians evaluated 5160 examinations to identify PEx. Machine learning models were trained using those parameters, and AUCs were calculated for PEx detection.

RESULTS: 522 self-examinations were diagnosed clinically as exacerbated. AI-aided home stethoscopes detected 415 exacerbated self-examinations (sensitivity 79.5 % at specificity 89.1 %). Among the single-parameter discriminators, coarse crackles intensity exhibited an AUC of 70 % (95% CI: 65-75) for young children, fine crackles intensity demonstrated an AUC of 75 % (95 % CI: 72-78) for older children, and an AUC of 93 % (95 % CI: 92-93) was achieved for adults using fine crackles intensity. The combination of parameters yielded the highest efficacy, with AUC exceeding 83% for objective parameters from the AI module alone and exceeding 90 % when incorporating both objective and subjective parameters across all groups.

CONCLUSIONS: The AI-aided home stethoscope has proven to be a reliable tool for detecting PEx with greater accuracy than self-assessment alone. Implementing this technology in healthcare systems has the potential to provide valuable insights for timely intervention and management of PExes.

PMID:39971691 | DOI:10.1016/j.jcf.2025.02.011

MMW Fortschr Med. 2025 Feb;167(Suppl 1):44-45. doi: 10.1007/s15006-024-4578-8.

NO ABSTRACT

PMID:39969735 | DOI:10.1007/s15006-024-4578-8

Biofilm. 2025 Jan 25;9:100257. doi: 10.1016/j.bioflm.2025.100257. eCollection 2025 Jun.

ABSTRACT

BACKGROUND: Pseudomonas aeruginosa chronic lung infection is the leading cause of death in the cystic fibrosis (CF) population. The high genome versatility of this microorganism allows it to adapt to the hostile CF lung where the same clone can persist for decades. Paranasal sinuses serve as a reservoir for bacterial adaptation before lung infection. Our study investigates biofilm compatibility among identical and different P. aeruginosa genotypes from sinus and lungs of CF patients. Strains were further characterized by whole genome sequencing and motility assays were performed.

METHODOLOGY: Motility, gentamicin susceptibility and growth rates were assessed in four strains coming from three CF patients. The strains were subjected to whole genome sequencing with the Illumina MiSeq platform.Conjugation assays using the mini Tn7 transposon were performed in order to tag bacteria with the fluorescent proteins YFP (yellow) and CFP (cyan). Biofilm experiments were carried out in a flow cell system and images were acquired using a confocal laser microscope (CLSM) on days 3 and 5. Four experiments were performed: Experiment 1 with two clonal isolates from sinus and lungs from patient P01 (CF430-142, CF430-11621); experiments 2 (CF430-11621 + 75885-B) and 3 (CF430-11621 + 80271-B) with two lung isolates belonging to two different clones from different patients (P02, P03) and experiment 4 with one lung strain (CF430-11621) and P. aeruginosa PAO1 reference strain.

RESULTS: P. aeruginosa clonal isolates coming from paranasal sinuses and lungs from the same patient were able to form mixed biofilm. When different clones were employed no mixed biofilms were observed. Similar results were observed when combining the lung strain and the reference strain PAO1. Biofilms of both strains were observed in the flow-cell channels but no mixed biofilms of them were observed, with the exception of strain 75887-B which did not appear to form any biofilm when mixed with strain CF430-11621. All strains performed swarming while strains CF430-142 and 75887B lacked twitching motility. An aminoacidic change in SadB was observed in the strain 75887B.

CONCLUSION: Mixed biofilms were only observed when identical clones from the same patient were cultured together. Our experiments indicate that twitching motility does not significantly affect biofilm formation or architecture in our isolates.

PMID:39968375 | PMC:PMC11834076 | DOI:10.1016/j.bioflm.2025.100257

Mycoses. 2025 Feb;68(2):e70034. doi: 10.1111/myc.70034.

ABSTRACT

BACKGROUND: Post-tuberculosis lung disease (PTLD) is a precursor to Aspergillus-related lung diseases. While Chronic Pulmonary Aspergillosis (CPA) has been extensively studied in the background of tuberculosis, Allergic Bronchopulmonary Aspergillosis (ABPA) has been reported sporadically with limited information on its prevalence, clinical-radiological features, and treatment outcomes.

OBJECTIVE: This study, conducted in a high TB burden setting, aimed to address this knowledge gap by systematically evaluating ABPA in PTLD patients.

METHODS: This retrospective cohort study screened PTLD patients presenting with respiratory or constitutional symptoms persisting for more than 3 months. The objective was to report the prevalence, clinical-radiological-laboratory data, and outcomes of ABPA-PTLD compared to a cohort of CPA (CPA-PTLD) and patients with PTLD (PTLD only).

RESULTS: Out of a total of 1012 PTLD patients, ABPA was seen in 2.27%, CPA in 20.75% and Aspergillus sensitization in 0.7%. ABPA patients primarily presented with breathlessness (91.3%) and cough (82.6%) while haemoptysis (43.5%), weight loss (13%), and anorexia (21.7%) were also observed, albeit less commonly than in CPA-PTLD. Bronchiectasis (100%) and nodules (87%) were more frequent in ABPA-PTLD patients, whereas consolidation (21.7%), cavities (30.4%), pleural thickening (8.7%), and 'fungal ball' (9.1%) were also seen, although less commonly than in CPA-PTLD. Most patients received azoles (78%) as first-line therapy, with symptomatic improvement (partial/complete) observed in ~78%.

CONCLUSION: ABPA may occur in PTLD patients, with specific clinical (e.g., haemoptysis) and radiological (e.g., cavity and fungal ball) features uncommon in other types of ABPA, but resembling other PTLD conditions. Future studies should focus on identifying differences in the natural course and appropriate treatment paradigms of ABPA-PTLD patients compared to ABPA occurring in asthma and cystic fibrosis patients.

PMID:39966329 | DOI:10.1111/myc.70034

Otol Neurotol. 2025 Jan 22. doi: 10.1097/MAO.0000000000004417. Online ahead of print.

ABSTRACT

OBJECTIVE: To provide the first description of intratympanic bacteriophage therapy for chronic mastoiditis from multidrug-resistant Pseudomonas aeruginosa in the United States.

PATIENTS: A 47-year-old woman with chronic mastoiditis in the setting of ciliary dysfunction from cystic fibrosis and immunosuppression from lung transplantation.

INTERVENTIONS: Ten concurrent parenteral and intratympanic doses of two custom phages targeting P. aeruginosa followed by IV antibiotic therapy.

MAIN OUTCOME MEASURES: Resolution of infection confirmed by symptomatology, cultures, and imaging.

RESULTS: At 5 months after phage treatment, the patient reported resolution of otorrhea, headaches, and hearing impairment. Subsequent cultures showed no growth.

CONCLUSIONS: Bacteriophages can enhance antibiotic activity in cases of drug-resistant chronic mastoiditis.

PMID:39965256 | DOI:10.1097/MAO.0000000000004417

J Clin Invest. 2025 Feb 18:e187778. doi: 10.1172/JCI187778. Online ahead of print.

ABSTRACT

Shwachman-Diamond syndrome (SDS) is characterized by neutropenia, exocrine pancreatic insufficiency, and bony abnormalities with an increased risk of myeloid neoplasia. Almost all cases of SDS result from biallelic mutations in SBDS. SBDS interacts with EFL1 to displace EIF6 from the 60S ribosomal subunit. Released EIF6 permits the assembly of ribosomal large and small subunits in the cytoplasm. Decreased EIF6 levels due to haploinsufficiency or missense mutations which lead to decreased protein expression may provide a somatic genetic rescue and anti-leukemic effects. We observed accumulation of EIF6 protein in sbds knockout (KO) zebrafish models, confirmed in patient-derived tissues, and correlated with changes in ribosome proteins and TP53 pathways. The mechanism of action for this adaptive response is unknown. To address this, we generated an eif6 zebrafish KO line which do not survive past 10 days post fertilization. We also created two mutants with low Eif6 expression, 5-25% of the wildtype levels, that can survive until adulthood. We bred them with sbds-null strains and analyzed their phenotype and biochemical properties. Low Eif6 levels reduced Tp53 pathway activation but did not rescue neutropenia in Sbds-deficient zebrafish. Further studies elucidating the interplay between SBDS, EIF6, TP53, and cellular stress responses offer promising insights into SDS pathogenesis, somatic genetic rescue, and therapeutic strategies.

PMID:39964763 | DOI:10.1172/JCI187778

BMC Pulm Med. 2025 Feb 17;25(1):81. doi: 10.1186/s12890-024-03455-2.

ABSTRACT

BACKGROUND: This study aimed to assess how Elexacaftor/Tezacaftor/Ivacaftor (ETI) influences lung function, Body Mass Index (BMI), Sweat Test (ST) and mental health of Cystic Fibrosis (CF) patients, emphasizing on depression and anxiety.

METHODS: We conducted an observational, prospective, multicentre study including 108 patients over 18 years old who initiated ETI therapy between December 2019 and December 2023. Patients underwent regular evaluations, including clinical, functional, and microbiological assessments, alongside completion of quality of life, anxiety, and depression questionnaires. We evaluated whether there was a difference in anxiety and depression levels over time.

RESULTS: After 12 months of treatment, significant improvements were noted in BMI, lung function (FEV1%), ST and various aspects of quality of life (CFQ-R). However, anxiety and depression levels did not differ significantly during the follow-up. When we stratified our sample by key groups, we observed that younger patients (under 28 years) and those with homozygous Phe508del mutations experienced significant higher anxiety with no differences on depression. Furthermore, anxiety and depression demonstrated a moderate correlation, strengthening over time.

CONCLUSIONS: Treatment with ETI establishes significant improvements in lung function, BMI, ST and quality of life in patients with CF. However, despite these positive outcomes, there were no significant changes observed in levels of anxiety and depression, except for individuals with homozygous mutation type and those younger than 28 years old, who exhibited significant higher levels of anxiety.

PMID:39962495 | DOI:10.1186/s12890-024-03455-2

JAMA Netw Open. 2025 Feb 3;8(2):e2460033. doi: 10.1001/jamanetworkopen.2024.60033.

ABSTRACT

IMPORTANCE: Donation after circulatory death (DCD) heart procurement has increased, but concerns remain about the effect of simultaneous heart and lung procurement, particularly with thoracoabdominal normothermic regional perfusion (TA-NRP), on the use of DCD lungs. Previous analyses exclude critical donor factors and organ nonuse, and rapidly rising DCD use may bias comparisons to historical controls.

OBJECTIVE: To use validated risk-adjusted models to assess whether DCD heart procurement via TA-NRP and direct procurement is associated with lung use.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study involved adult DCD donors between January 1, 2019, and September 30, 2024, listed in the Scientific Registry of Transplant Recipients (SRTR). The SRTR deceased donor yield model was used to develop an observed to expected (O:E) yield ratio of lung use obtained through DCD among 4 cohorts: cardiac DCD donors vs noncardiac DCD donors and cardiac DCD donors undergoing TA-NRP vs direct procurement. Temporal trends in O:E ratios were analyzed with the Cochran-Armitage test.

MAIN OUTCOMES AND MEASURES: The O:E ratios of DCD lung use.

RESULTS: Among 24 431 DCD donors (15 878 [65.0%] male; median [IQR] age, 49.0 [37.0-58.0] years), 22 607 were noncardiac DCD (14 375 [63.6%] male; median [IQR] age, 51.0 [39.0-58.0] years) and 1824 were cardiac DCD (1503 [82.4%] male; median [IQR] age, 32.0 [26.0-38.0] years) donors; noncardiac DCD donors were more likely to be smokers (6873 [30.4%] vs 227 [12.4%]; P < .001). Among cardiac DCD donors, 325 underwent TA-NRP, while 712 underwent direct procurement. TA-NRP donors had shorter median (IQR) lung ischemic times (6.07 [4.38-9.56] hours vs 8.12 [6.16-12.00] hours; P < .001) and distances to recipient hospitals (222 [9-626] nautical miles vs 331 [159-521] nautical miles; P = .050) than direct procurement donors. Lung use was higher among cardiac DCD donations compared with noncardiac DCD donations (16.7% vs 4.4%, P < .001). Within the cardiac DCD cohort, lung use was similar between TA-NRP and direct procurement (19.1% vs 18.7%; P = .88) cohorts. Both noncardiac DCD and cardiac DCD donors had observed lung yields greater than expected (O:E, 1.29 [95% CI, 1.21-1.35] and 1.79 [95% CI, 1.62-1.96]; both P < .001), although cardiac DCD yield was significantly higher than noncardiac DCD yield (P < .001). Both TA-NRP and direct procurement lung yields were greater than expected (O:E, 2.00 [95% CI, 1.60-2.43] and 1.77 [95% CI, 1.52-1.99]; both P < .001) but were not significantly different from each other (P = .83). The O:E ratios did not change significantly over time across all cohorts. Among recipients, the TA-NRP cohort experienced significantly better 90-day mortality (0 of 62 vs 9 of 128 patients [7.0%]; P = .03) and overall survival (4 of 62 patients [6.5%] vs 21 of 128 patients [16.4%]; P = .04) rates compared with the direct procurement cohort.

CONCLUSIONS AND RELEVANCE: In this cohort study of DCD donors, concomitant heart procurement provided better-than-expected rates of lung use as assessed with validated O:E use ratios regardless of procurement technique. The findings also suggest a survival benefit with improved 90-day and overall survival rates for the TA-NRP cohort compared with the direct procurement cohort. Policies should be developed to maximize the benefits of these donations.

PMID:39960670 | PMC:PMC11833517 | DOI:10.1001/jamanetworkopen.2024.60033

Respir Med. 2025 Feb 15:107995. doi: 10.1016/j.rmed.2025.107995. Online ahead of print.

NO ABSTRACT

PMID:39961395 | DOI:10.1016/j.rmed.2025.107995