Scand J Med Sci Sports. 2025 Jan;35(1):e70018. doi: 10.1111/sms.70018.

ABSTRACT

Previous studies in sports science suggested that regular exercise has a positive impact on human health. However, the effects of endurance sports and their underlying mechanisms are still not completely understood. One of the main debates regards the modulation of immune dynamics in high-intensity exercise. As part of the "Run 4 Science" project in Verona, Italy, we conducted a single-cell RNA sequencing analysis on half-marathon amateur runners to investigate the transcriptional dynamics of peripheral blood mononuclear cells following endurance exercise. Blood samples were collected from four participants before and after running a half-marathon to carry out a comprehensive transcriptomic analysis of immune cells at the single-cell level. Our analysis revealed significant alterations in the transcriptional profiles following endurance physical exercise. Modulations in myeloid cells suggested the activation of stress response (6 related pathways, p < 0.04) and pathways related to viral processes (4 related pathways, p < 0.03), while in lymphoid cells they hinted to a shift towards immune activation (24 related pathways, p < 0.01). Additionally, transcriptional changes in platelets point to an activation of the coagulation process (5 related pathways, p < 0.005). Single-cell data was also analyzed following a pseudo-bulk approach (i.e., simulating a bulk RNAseq experiment) to gain further biological insights. Our findings suggest that a pseudo-bulk analysis could offer complementary findings to classical single-cell analysis methods and demonstrate that endurance physical exercise, such as running a half-marathon, induces substantial changes in the transcriptional dynamics of immune cells. These insights contribute to a better understanding of the immune modulation mediated by endurance exercise and may inform future training routines or nutritional guidelines based on individual gene expression levels.

PMID:39817606 | DOI:10.1111/sms.70018

Mol Genet Metab Rep. 2024 Dec 26;42:101182. doi: 10.1016/j.ymgmr.2024.101182. eCollection 2025 Mar.

ABSTRACT

BACKGROUND: Immediately after birth, adaptation to the extrauterine environment includes an upregulation of fatty acid catabolism. Cystic fibrosis and untreated hypothyroidism exert a life-long impact on fatty acid metabolism, but their influence during this transitional period is unknown. Children and adults with cystic fibrosis exhibit unbalanced fatty acid composition, most prominently a relative deficit of linoleic acid. Lipid catabolism is downregulated in hypothyroidism.

METHODS: We analyzed acylcarnitine data in newborn screening blood spot samples from infants with cystic fibrosis, with congenital hypothyroidism, or without congenital disorders. Eight long-chain acylcarnitine species were quantified. Of primary interest was the relative composition of linoleoylcarnitine (C18:2), the acylcarnitine of linoleic acid. Mixed effects modeling was used to determine the impact of disease status on acylcarnitine levels, accounting for possible covariates including birth weight, gestational age, sex and race.

RESULTS: Total long-chain acylcarnitine levels were diminished in newborns with cystic fibrosis and with congenital hypothyroidism. Contrary to expectations, C18:2 composition was elevated in newborns with cystic fibrosis and with congenital hypothyroidism, as compared to those without congenital disorders. Furthermore, higher thyroid-stimulating hormone levels, indicative of more severe hypothyroidism, predicted higher C18:2 composition.

CONCLUSIONS: Decreased total long-chain acylcarnitine concentrations in newborns with cystic fibrosis and congenital hypothyroidism suggest diminished beta-oxidation. However, the unexpected relative increase in C18:2 indicates selective preservation of linoleic acid beta-oxidation in both conditions. This is especially surprising in cystic fibrosis where linoleic acid levels become diminished and suggests that linoleic acid beta-oxidation contributes to the deficiency of linoleic acid in cystic fibrosis.

PMID:39816991 | PMC:PMC11732690 | DOI:10.1016/j.ymgmr.2024.101182

Mycoses. 2025 Jan;68(1):e70024. doi: 10.1111/myc.70024.

ABSTRACT

BACKGROUND: The airways of patients with cystic fibrosis (pwCF) harbour complex fungal and bacterial microbiota involved in pulmonary exacerbations (PEx) and requiring antimicrobial treatment. Descriptive studies analysing bacterial and fungal microbiota concomitantly are scarce, especially using both culture and high-throughput-sequencing (HTS).

OBJECTIVES: We analysed bacterial-fungal microbiota and inter-kingdom correlations in two French CF centres according to clinical parameters and antimicrobial choices.

METHODS: Forty-eight pwCF with PEx from Creteil (n = 24) and Lille (n = 24) CF centres were included over 2 years. Sputa were collected for culture and targeted-HTS (ITS2 and V3-V4 targets). Sequencing and culture data, along with clinical, radiological and treatment data, were analysed. Two-level stratified analysis was performed to study potential confounding factors (age, CF mutation, FEV1 and antibiotics) on the centre factor. Inter-kingdom correlations were analysed.

RESULTS: Significant differences in the bacterial microbiota profile were found between centres (p-value = 0.03). For mycobiota, the taxonomic distribution and diversity were comparable. HTS provided concordant but more detailed information than culture and increased detection of main CF fungi (> 25% more positive samples for Aspergillus or Scedosporium). FEV1 and systemic antibiotic before PEx influenced bacterial microbiota, but no clinical association was found with the mycobiota. No inter-kingdom correlation between Pseudomonas and fungi was found.

CONCLUSIONS: Describing concomitant bacterial and fungal communities of pwCF at the beginning of PEx using culture and HTS shows greater diversity in HTS and better detection in case of low microbial load. Interesting inter-kingdom correlations were observed, requiring further research on larger cohorts to understand the potential microbial interactions.

PMID:39816006 | DOI:10.1111/myc.70024

J Cyst Fibros. 2025 Jan 14:S1569-1993(25)00010-4. doi: 10.1016/j.jcf.2025.01.010. Online ahead of print.

ABSTRACT

BACKGROUND: Whether improvements in gastrointestinal (GI) symptoms observed with Elexacaftor/Tezacaftor/Ivacaftor (ETI) treatment are sustained in the longer-term requires exploration. This study investigated how GI-symptoms change with longer-term ETI use in pancreatic insufficient adults with cystic fibrosis (awCF).

METHODS: Participants completed up to three abdominal symptom questionnaires, employing the validated CFAbd-Score. Changes in total CFAbd-Score and its five domains, pain, gastroesophageal reflux-disease (GERD), disorders of bowel movement (DBM), disorders of appetite (DA) and quality of life (QOL), were analysed pre-ETI (T0) and at ≤1.5 years (T1) and 2-4 years of ETI-therapy (T2).

RESULTS: A total of 165 CFAbd-Scores from 68 participants were analysed (median age: 34 years; IQR: 28-39). Total CFAbd-Score significantly (p < 0.05) and clinically meaningfully decreased from 20.4 ± 1.6 pre-ETI (median:40 weeks pre-treatment) to 15.3 ± 1.9 and 16.8 ± 1.6 at T1 (median: 25 weeks of ETI) and T2 (median: 148 weeks of ETI), respectively. The CFAbd-Score´s domains DA and QoL only significantly decreased between T0 and T1, whereas DBM only significantly decreased after 2-4 years of ETI therapy (T2). GERD scores were significantly lower at both T1 and T2.

CONCLUSION: While GI symptoms in awCF significantly improve within the first 1.5 years of ETI-therapy, they appear to somewhat wane with longer-term use, despite GI-symptom burden still being lower compared to pre-ETI. However, we cannot differentiate whether this results from reduced adherence, a decrease in ETI effects, or long-term changes in diet, gut microbiota or symptom perception. The longer-term impact of ETI and other potential modulator therapies on GI symptoms requires ongoing monitoring.

PMID:39814671 | DOI:10.1016/j.jcf.2025.01.010

Exp Clin Endocrinol Diabetes. 2025 Jan 15. doi: 10.1055/a-2460-6977. Online ahead of print.

ABSTRACT

The issue of a possible association between Shwachman-Diamond Syndrome and diabetes has been debated for many years. This review updates the Italian Shwachman-Diamond registry, confirming our previous findings that suggest that these patients might be at higher risk of developing diabetes, particularly type 1. These data are of relevance in the clinical follow-up of patients in everyday life, emphasizing the need for early diagnosis and timely intervention.

PMID:39814041 | DOI:10.1055/a-2460-6977

Microbiol Res. 2025 Jan 9;293:128052. doi: 10.1016/j.micres.2025.128052. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa is a prominent respiratory pathogen in cystic fibrosis (CF) patients, thriving in the hypoxic airway mucus. Previous studies have established the role of the oxygen-binding hemerythrin, Mhr, in enhancing P. aeruginosa's fitness under microaerobic conditions. However, the specific mechanisms by which Mhr operates remain unclear. This study uniquely identifies Mhr as an effector of the H2-Type VI Secretion System (H2-T6SS) and elucidates its role in the transport and interaction mechanisms that confer a growth advantage under microaerobic conditions. Our findings demonstrate that mhr expression is directly regulated by Anr and Dnr. Western blot analysis confirms that Mhr is secreted extracellularly via the H2-T6SS. The oxygen-binding Mhr re-enters P. aeruginosa through the OprG porin. Then, Mhr interacts with cbb3-type cytochrome c oxidase (cbb3-CcO) subunits CcoP1/CcoP2, significantly impacting intracellular NADH/NAD+ levels. These insights suggest that the T6SS-mediated secretion and transport of Mhr represent a novel mechanism by which P. aeruginosa acquires and delivers oxygen, potentially enhancing microaerobic respiration, energy production, and growth under microaerobic conditions.

PMID:39813750 | DOI:10.1016/j.micres.2025.128052

J Bras Pneumol. 2025 Jan 13;50(6):e20240301. doi: 10.36416/1806-3756/e20240301. eCollection 2025.

ABSTRACT

OBJECTIVE: Surgical resection remains the gold standard treatment for bronchiectasis in patients who present with hemoptysis or suppuration, as well as in those who do not respond to clinical treatment. We sought to investigate the efficacy of sublobar resection (segmentectomy) and compare it with that of lobar resection (lobectomy) in patients with non-cystic fibrosis bronchiectasis.

METHODS: Patients undergoing lobectomy or segmentectomy between 2019 and 2023 were included in the study. We analyzed intraoperative complications and postoperative outcomes, including length of hospital stay, length of ICU stay, and disease recurrence.

RESULTS: There was no significant difference between the lobectomy and segmentectomy groups regarding the occurrence of intraoperative complications such as bleeding > 1000 ml, cardiogenic shock, and ventilatory instability (p > 0.999). However, the frequency of complications was significantly lower in the segmentectomy group than in the lobectomy group (p = 0.016). Hospital stays were longer in the lobectomy group than in the segmentectomy group (16 days vs. 5 days; p = 0.027), as were ICU stays (7 days vs. 1 day; p = 0.006). There was no significant difference between the lobectomy and segmentectomy groups regarding the recurrence rate (p = 0.541).

CONCLUSIONS: Early identification of bronchiectasis patients who are candidates for surgical resection is essential because those who are identified as such early on are candidates for parenchyma-sparing resections, which are similar to lobar resections in terms of disease control and lead to shorter hospital stays and better postoperative outcomes.

PMID:39813502 | DOI:10.36416/1806-3756/e20240301

PLoS One. 2025 Jan 15;20(1):e0317054. doi: 10.1371/journal.pone.0317054. eCollection 2025.

ABSTRACT

The epidemiology of allergic bronchopulmonary aspergillosis (ABPA) in the United States is not well-described. To estimate national ABPA prevalence among patients with asthma or cystic fibrosis, characterize ABPA testing practices, and describe ABPA clinical features, treatment, and 6-month outcomes. We used the 2016-2022 Merative™ MarketScan® Commercial/Medicare and Multi-State Medicaid Databases to identify cohorts of patients with 1) asthma, 2) cystic fibrosis (CF), and 3) ABPA. We calculated ABPA prevalence per 10,000 patients with asthma or CF, assessed diagnostic testing for ABPA among patients with severe asthma, and described features of patients with ABPA using diagnosis and procedure codes. The overall ABPA prevalence among patients with asthma was 2.8/10,000 (Commercial/Medicare) and 1.0/10,000 (Medicaid). ABPA prevalence increased with asthma severity (Commercial/Medicare: mild 1.3, moderate 9.3, severe 70.6, Medicaid: mild 0.3, moderate 2.4, severe 32.4). Among patients with CF, ABPA prevalence was 183.7/10,000 (Commercial/Medicare) and 134.6/10,000 (Medicaid). Among patients with severe asthma, 10.3% (Commercial/Medicare) and 7.4% (Medicaid) received total immunoglobulin E testing, which is recommended for ABPA diagnosis. Among all patients with ABPA (Commercial/Medicare: n = 1,564, Medicaid: n = 410), ABPA treatments included inhaled corticosteroids (>70%), systemic corticosteroids (>62%), and antifungals (>18%). Patients with ABPA and Medicaid were more likely to experience hospitalization (45.1% vs. 22.5% of patients with Commercial/Medicare insurance) and respiratory failure (18.5% vs. 10.9%). This analysis provides initial estimates of national ABPA prevalence. Further studies could identify potential barriers to ABPA testing and investigate potential factors affecting payer-related differences in ABPA burden.

PMID:39813272 | DOI:10.1371/journal.pone.0317054

Proc Natl Acad Sci U S A. 2025 Jan 21;122(3):e2412717122. doi: 10.1073/pnas.2412717122. Epub 2025 Jan 15.

ABSTRACT

Monocytes are critical in controlling tissue infections and inflammation. Monocyte dysfunction contributes to the inflammatory pathogenesis of cystic fibrosis (CF) caused by CF transmembrane conductance regulator (CFTR) mutations, making CF a clinically relevant disease model for studying the contribution of monocytes to inflammation. Although CF monocytes exhibited adhesion defects, the precise mechanism is unclear. Herein, superresolution microscopy showed that an integrin clustering but not an integrin activation defect determines the adhesion defect in CFTR-deficient monocytes, challenging the existing paradigm emphasizing an integrin activation defect in CF patient monocytes. We further found that the clustering defect is accompanied by defects in CORO1A membrane recruitment, actin cortex formation, and CORO1A engagement with integrins. Complementing canonical studies of leukocyte adhesion focusing on integrin activation, we highlight the importance of integrin clustering in cell adhesion and report that integrin clustering and activation are distinctly regulated, warranting further investigation for selective targeting in therapeutic strategy design involving leukocyte-dependent inflammation.

PMID:39813254 | DOI:10.1073/pnas.2412717122

Inflamm Bowel Dis. 2025 Jan 15:izae302. doi: 10.1093/ibd/izae302. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Patients with very early-onset inflammatory bowel disease (VEO-IBD), with an age of onset < 6 years, can present with severe manifestations and may require biologic therapy. Infliximab and adalimumab are approved for induction and maintenance in pediatric IBD patients but are licensed only above the age of 6 years. Effectiveness and safety data on adalimumab in this patient population are lacking. We assessed the therapeutic response to help close this gap.

METHODS: This retrospective study involved 30 sites worldwide. Demographic, clinical, and laboratory data were collected from patients with VEO-IBD who commenced adalimumab therapy before the age of 6 years.

RESULTS: Seventy-eight patients (37 Crohn's disease, 26 ulcerative colitis, and 15 with IBD-unclassified) were included. Median age of IBD onset was 2.6 (1.3-4.1) years, with 30 (38.5%) patients diagnosed at age <2 years. Median age at adalimumab initiation was 4.2 (2.8-5.1) years. Adalimumab was used as second-line biologic therapy in 45 (57.7%) patients after infliximab. The median time to last follow-up was 63 (22-124) weeks. Significant improvement in clinical scores, CRP, fecal calprotectin, and weight Z-score were observed by Week 52. Adalimumab durability rates were 61.9%, 48.1%, and 35.6% after 1, 2, and 3 years, respectively. Drug discontinuation rates were not dependent on IBD type, age, prior anti-TNF exposure, or concomitant immunomodulatory treatment. Four (5.1%) patients developed serious infections, including 1 patient with TTC7A deficiency who died following adenovirus sepsis.

CONCLUSION: Adalimumab therapy is a viable therapeutic option in patients with VEO-IBD with an acceptable safety profile.

PMID:39813158 | DOI:10.1093/ibd/izae302

Pediatr Pulmonol. 2025 Jan;60(1):e27472. doi: 10.1002/ppul.27472.

ABSTRACT

BACKGROUND: The vast majority of men with CF (mwCF) are infertile. Improvements in assisted reproductive technology (ART) have made it possible for these patients to become biological fathers.

METHODS: Data were examined for all male CF patients attending a large adult CF center over a 23-year period. Azoospermia was confirmed via laboratory analysis of semen and was defined as complete absence of sperm in the ejaculate. Outcome of surgical sperm retrieval (SSR) procedure, post SSR complications, success rate of intracytoplasmic sperm injection (ICSI) and embryo transfer and subsequent live births were evaluated.

RESULTS: Seventy-one mwCF with proven azoospermia were referred to fertility services over the study period. Mean (SD) percentage predicted forced expiratory volume in 1 second (ppFEV1) 67.86 ( ± 25.3), body mass index (BMI) 24.3 ( ± 3.7) kg/m2. Seventy (98.5%) of these men underwent and had successful SSR. 67/71 (94%) couples proceeded to have ICSI post SSR. 11 couples had failed egg fertilisation, implantation, or early miscarriage. 56/67 couples (84%) went on to have live births. To date 10/71 (14%) mwCF referred for fertility treatment have died. Mean ppFEV1 and BMI of mwCF who survived was higher than those who died; FEV1 72.8% ( ± 23.4) versus 38% ( ± 12.0) (p < 0.001), BMI 25.0 ( ± 3.5) kg/m2 versus 20.3 ( ± 2.2) kg/mg2 (p < 0.001).

CONCLUSION: This is the largest study to investigate success rate of fertility treatment in mwCF and demonstrates that fertility treatment is successful in greater than 75% of patients referred. Clinical status and prognosis remain important factors when considering referral to fertility services.

PMID:39812352 | DOI:10.1002/ppul.27472

Pediatr Pulmonol. 2025 Jan;60(1):e27483. doi: 10.1002/ppul.27483.

ABSTRACT

BACKGROUND: Notwithstanding guidance from the European Cystic Fibrosis (CF) Society (ECFS) neonatal screening (NBS) working group, significant variation persists in the evaluation and management of Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CFSPID) subjects, leaving many aspects of care under debate. This study reports the results of a national survey investigating management and treatment approaches of pre-school CFSPIDs in Italy.

METHODS: In February 2024, a comprehensive questionnaire was distributed to all Italian CF centers. The survey explored various aspects of CFSPID management in the year 2023, including patient visit schedules, sweat tests (ST) timing, screening procedures, therapeutic interventions, and discharge criteria. Data on regional NBS protocols, number of CFSPID cases, and CF:CFSPID ratio were also collected.

RESULTS: By December 31, 2023, CF Italian centers were following 522 CFSPIDs. In 2023, CF NBS identified 85 CF and 68 CFSPID cases, resulting in a CF:CFSPID ratio of 1.25:1. Seven centers diagnosed more CFSPID than CF, with the lowest CF:CFSPID ratio being 0.20:1. A quarter of all centers reported management plans that deviated widely from ECFS guidelines. Respiratory cultures were performed in 16 (69.6%) centers in the absence of symptoms. Nine (38.9%) prescribed antibiotics in any case of positive Pseudomonas aeruginosa cultures, including first detections and asymptomatic subjects. Spirometries were performed by 14/23 centers (60.9%) in procedure-competent children at each visit. Follow up care continued after age 6 for all CFSPIDs in 15 (65.2%) centers regardless of age, genotype or ST results. A diagnosis of CF was established based on repeated pathological STs and/or multiorgan involvement. Children with STs in intermediate range and mono-organ involvement were classified as CFTR-related disorders (CFTR-RD).

CONCLUSIONS: Despite available data on clinical course and recommendations on management of CFSPIDs, different approaches persist in clinical practice. Further efforts should be considered to disseminate and encourage adherence to international guidelines.

PMID:39812351 | DOI:10.1002/ppul.27483

Int Forum Allergy Rhinol. 2025 Jan 15. doi: 10.1002/alr.23533. Online ahead of print.

NO ABSTRACT

PMID:39811887 | DOI:10.1002/alr.23533

Biofilm. 2024 Dec 20;9:100246. doi: 10.1016/j.bioflm.2024.100246. eCollection 2025 Jun.

ABSTRACT

Biofilm infections are chronic infections which are difficult to diagnose. Biofilm infections are tolerant to antibiotics and the defense mechanisms of the host. Patients with the genetic disease cystic fibrosis (CF) produce viscid mucus in the respiratory tract and therefore suffer from chronic biofilm infections in their lungs and paranasal sinuses. The most important microorganism is the mucoid phenotype of Pseudomonas aeruginosa which causes chronic biofilm infections in the lungs of CF patients and untreated patients succumb as children if they contact this biofilm infection. Since CF patients are treated in CF Centers all over the world, it is possible to do longitudinal studies on epidemiology, pathophysiology, diagnosis, prevention and treatment of P. aeruginosa biofilm infection which is not possible if such patients are not followed in specialized centers. This survey describes the research through several decades in the Danish CF Center in Copenhagen which have changed the epidemiology, treatment, prophylaxis and prognosis of CF patients worldwide. Based on these results ESCMID Guidelines for diagnosis and treatment of biofilm infections were published which have influenced biofilm research and treatment in other areas.

PMID:39811797 | PMC:PMC11732244 | DOI:10.1016/j.bioflm.2024.100246

ERJ Open Res. 2025 Jan 13;11(1):00137-2024. doi: 10.1183/23120541.00137-2024. eCollection 2025 Jan.

ABSTRACT

BACKGROUND: Chronic rhinosinusitis (CRS) and olfactory dysfunction (OD) are prevalent disease complications in people with cystic fibrosis. These understudied comorbidities significantly impact quality of life. The impact of highly effective modulator therapy (HEMT) in young children with cystic fibrosis (YCwCF) on these disease complications is unknown. This proposed study aims to characterise CRS and OD in YCwCF and assess the efficacy of HEMT in improving sinus and olfactory health in this young age group.

METHODS: This six-centre, prospective, observational study will enrol 80 YCwCF aged 2-8 years. Patients are divided into two groups: those receiving HEMT and those not on HEMT based on clinical indication. Both groups undergo sinus magnetic resonance imaging, psychophysical olfactory tests, and complete patient- or parent-reported quality of life surveys over 2 years. Outcomes will be compared before and after initiation of HEMT and between groups. Ethical approval has been obtained for all sites, and this study has been registered on ClinicalTrials.gov (NCT06191640).

RESULTS: Enrolment began in April 2023. 21 participants have been enrolled as of October 2023 with ongoing enrolment at all sites.

CONCLUSION: This investigation is expected to provide critical insights into the potential benefits of early HEMT initiation in managing CRS and OD in YCwCF. It will assist in developing targeted interventions and contribute to the understanding of HEMT's role in altering the disease course in this demographic.

PMID:39811548 | PMC:PMC11726580 | DOI:10.1183/23120541.00137-2024

ERJ Open Res. 2025 Jan 13;11(1):00587-2024. doi: 10.1183/23120541.00587-2024. eCollection 2025 Jan.

ABSTRACT

BACKGROUND: People with cystic fibrosis (CF) variants that exhibit residual function (RF) of the CF transmembrane conductance regulator are considered to have a milder disease; however, the spectrum of CF phenotype within the different RF variants has not been extensively investigated. The aim of the present study was to characterise the spectrum of CF disease severity in people with CF (pwCF) carrying different RF variants, using the European Cystic Fibrosis Society Patient Registry (ECFSPR) data.

METHODS: A retrospective cross-sectional and longitudinal cohort study included data from the ECFSPR during 2008-2016. Demographic and clinical characteristics of pwCF carrying different RF variants were compared with the characteristics of pwCF who are homozygous for F508del. Among those with RF, a distinction was made between pwCF carrying class IV or class V variants and pwCF carrying specific RF variants.

RESULTS: Out of 56 701 pwCF in the ECFSPR, 6192 carried RF variants and 22 766 were homozygous for F508del. Class IV/F508del variants were associated with a milder course than class V/F508del; both were milder than pwCF homozygous for F508del. Forced expiratory volume in 1 s % predicted (FEV1pp) declined in childhood in all groups. For adults, the hazard ratio of death for class V/F508del versus class IV/F508del was 2.14 (95% confidence interval 0.99-4.63, p=0.052). PwCF carrying 3849+10 kb C→T/F508del and pwCF carrying R334W/F508del had age-specific FEV1pp and chronic bacterial colonisation similar to those of pwCF homozygous for F508del.

CONCLUSION: There is a wide spectrum of disease severity between the different RF variants. Some, such as those carrying 3849+10 kb C→T, have severe disease, similar to that of pwCF homozygous for F508del.

PMID:39811546 | PMC:PMC11726569 | DOI:10.1183/23120541.00587-2024

IDCases. 2024 Dec 15;39:e02132. doi: 10.1016/j.idcr.2024.e02132. eCollection 2025.

ABSTRACT

Mycobacterium Chelonae is a rapidly growing nontuberculous mycobacterium (NTM) that is ubiquitous in the environment and is associated with skin and soft tissue infections (1). Because Mycobacterium Chelonae is an opportunistic infection, it can present as skin abscess, cellulitis, osteomyelitis, pulmonary infection or disseminated infections, particularly in individuals with compromised immune systems or underlying lung conditions such as cystic fibrosis or bronchiectasis. M.Chelonae is one of the most pathogenic rapidly growing mycobacteria (RGM). Diagnosing RGM and distinguishing it from Mycobacterium tuberculosis is important because public health tracking and management is different in these two organisms. Antibiotic susceptibility testing can also provide valuable clues to the species identification of RGM as each species has a specific in vitro antibiotic susceptibility pattern (2). Although incidence of M. Chelonae is increasing, these infections often remain misdiagnosed. This case report discusses the clinical presentation, diagnostic challenges, the rationale for early empiric treatment, and therapeutic options for M. Chelonae infection, emphasizing the importance of timely intervention in immunocompromised individuals.

PMID:39810811 | PMC:PMC11732071 | DOI:10.1016/j.idcr.2024.e02132

Heliyon. 2024 Dec 17;11(1):e41324. doi: 10.1016/j.heliyon.2024.e41324. eCollection 2025 Jan 15.

ABSTRACT

BACKGROUND: Due to its increasing prevalence and suboptimal treatment, non-tuberculous mycobacterial (NTM) infection is an emerging problem in patients with cystic fibrosis (CF). Detailed description of regional NTM prevalence and distribution, and identification of predictors of NTM acquisition in CF are essential to optimise treatment and surveillance guidelines.

METHODS: A retrospective, multi-center analysis was conducted between the years 2020 and 2022 on data from 232 adult patients registered in the Hungarian CF Registry in 2022. In a case-control analysis of NTM-positive (n = 39) and NTM-negative (n = 73) CF patients, demographic, clinical, and microbiological data were analysed to identify potential predictors for NTM acquisition. The distribution of NTM species, their antibiotic susceptibility patterns were also evaluated.

RESULTS: The prevalence of NTM-positive sputum increased from 4.7 % to 12.9 % over study period. The most prevalent NTMs were M. avium complex (41.0 %), M. abscessus complex (MABSC) (38.5 %) and M. xenopi (15.4 %). MABSC strains were highly resistant to doxycycline, fluoroquinolones, and sulfonamides, while amikacin, macrolides, tigecycline and linezolid were often effective. Forced expiratory volume in 1 s (FEV1) was lower in the NTM-positive group at the index date and 1 and 2 years before NTM detection (p < 0.01), predicting NTM infection. Previous NTM-positive sputum culture enhanced the risk of NTM reacquisition in the airway (odds ratio: 7).

CONCLUSION: The results demonstrate a high prevalence of NTM in the Hungarian adult CF population and a high rate of multidrug-resistant MABSC isolates in their sputum. The risk of acquiring airway NTM is higher in CF patients with significantly impaired lung function and previous respiratory mycobacteriosis.

PMID:39807497 | PMC:PMC11728951 | DOI:10.1016/j.heliyon.2024.e41324

BMJ Open. 2024 Dec 22;14(12):e087798. doi: 10.1136/bmjopen-2024-087798.

ABSTRACT

INTRODUCTION: Living with a chronic disease impacts many aspects of life, including the ability to participate in activities that enable interactions with others in society, that is, social participation (SP). Despite efforts to monitor the quality of care and life of chronically ill people in Belgium, no disease-specific patient-reported measures (PRMs) have been used. These tools are essential to understand SP and to develop evidence-based recommendations to support its improvement. This protocol presents the phases for the disease-specific development of patient-reported outcome and experience measures to assess SP and its potential determinants among people living in Belgium with cancer, cystic fibrosis, diabetes, HIV or a neuromuscular disease.

METHODS AND ANALYSIS: This protocol applies the PROMIS Instrument Development and Validation Scientific Standards and COnsensus-based Standards for the selection of health Measurement INstruments to develop PRMs in a disease-specific manner to quantify the components of the International Classification of Functioning, Disability and Health (ICF). A mixed-method approach is used to create broad initial item pools based on patient (focus groups) and literature perspectives which are compared within ICF-standardised language by applying the refined ICF linking rules. An item set is first created based on this cross-matching exercise and then validated by multidisciplinary expert panels. Cognitive assessment and pilot testing are followed by the dissemination of the survey to a representative sample in Belgium. Advanced psychometric testing (classical test theory and item response theory) is applied to inform an item reduction strategy for the final measures and to develop scales for the ICF components.

ETHICS AND DISSEMINATION: Ethical approval was granted by the Ethics Committee of the Ghent University Hospital on 20 February 2023 to organise the patient focus groups (ONZ-2022-0470). Ethical approval for dissemination of the PRMs and psychometric testing will be sought at the Ghent University Hospital Ethics Committee at the start of Phase 6. Results will be disseminated through peer-reviewed journals and professional conferences.

PMID:39806694 | DOI:10.1136/bmjopen-2024-087798

BMJ Open. 2024 Dec 20;14(12):e092747. doi: 10.1136/bmjopen-2024-092747.

ABSTRACT

INTRODUCTION: Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, primarily affecting the respiratory and digestive systems. Respiratory rehabilitation techniques play a crucial role in managing pulmonary symptoms and maintaining lung function in CF patients. Although various techniques have been developed and applied, there is currently no globally recognised optimal respiratory rehabilitation regimen. This study intends to conduct a network meta-analysis to comprehensively evaluate and compare the effectiveness of different respiratory rehabilitation techniques in CF patients.

METHODS AND ANALYSIS: The following key electronic bibliographic databases will be searched from inception to September 2024: Medline, Embase, Cochrane Library, Web of Science, CINAHL and Physiotherapy Evidence Database. We will include randomised controlled trials (RCTs) and quasi-RCTs that compare the efficacy of various respiratory rehabilitation techniques in CF patients, such as airway clearance techniques, exercise training and inspiratory muscle training. The primary outcomes will be lung function (forced expiratory volume in 1 s and forced vital capacity) and exercise capacity (VO2 max and 6 min walk test). Secondary outcomes will include quality of life, frequency of pulmonary exacerbations, hospitalisation rates and adverse events. If permitted, data will be synthesised using traditional pairwise meta-analysis and network meta-analysis, with the quality of evidence assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

ETHICS AND DISSEMINATION: Ethical approval will not be required for this protocol. The results of the final review will be disseminated via peer-reviewed journals and conference presentations.

PROSPERO REGISTRATION NUMBER: CRD42024574551.

PMID:39806674 | DOI:10.1136/bmjopen-2024-092747