Breastfeed Med. 2024 Dec 26. doi: 10.1089/bfm.2024.0391. Online ahead of print.

NO ABSTRACT

PMID:39723933 | DOI:10.1089/bfm.2024.0391

Biometrics. 2024 Oct 3;80(4):ujae150. doi: 10.1093/biomtc/ujae150.

ABSTRACT

In many clinical contexts, the event of interest could occur multiple times for the same patient. Considerable advancement has been made on developing recurrent event models based on or that use biomarker information. However, less attention has been given to evaluating the prognostic accuracy of a biomarker or a composite score obtained from a fitted recurrent event-rate model. In this manuscript, we propose novel measures to characterize the prognostic accuracy of a marker measured at baseline in the presence of recurrent events. The proposed estimators are based on a semiparametric frailty model that accounts for the informativeness of a marker and unobserved heterogeneity among patients with respect to the rate of event occurrence. We investigate the asymptotic properties of the proposed accuracy estimators and demonstrate these estimators' finite sample performance through simulation studies. The proposed estimators have minimal bias and appropriate coverage. The estimators are applied to evaluate the performance of a baseline forced expiratory volume, a measure of lung capacity, for repeated episodes of pulmonary exacerbations in patients with cystic fibrosis.

PMID:39723565 | DOI:10.1093/biomtc/ujae150

Front Genet. 2024 Dec 11;15:1477940. doi: 10.3389/fgene.2024.1477940. eCollection 2024.

ABSTRACT

INTRODUCTION: Infantile hypotonia with psychomotor retardation and characteristic facies-1 (IHPRF1, MIM#615419) is a rare, birth onset, autosomal recessive disorder caused by homozygous or compound heterozygous truncating variants in NALCN gene (MIM#611549) resulting in a loss-of-function effect.

METHODS: We enrolled a new IHPRF1 patients' cohort in the framework of an international multicentric collaboration study. Using specialized in silico pathogenicity predictors and ad hoc structural analyses, we assessed the mechanistic consequences of the deleterious variants retrieved on NALCN structure and function.

RESULTS: To date 38 different NALCN variants have been retrieved from 33 different families, 26 from unrelated and 22 from related patients. We report on five new IHPRF1 patients from four different families, harboring four newly identified and one previously retrieved variant that exhibited a markedly significant functional impact, thereby compromising the functionality of the protein complex.

DISCUSSION: By widening the functional spectrum of biallelic variants affecting the NALCN gene, this article broadens the IHPRF1 syndrome's genotype-phenotype correlation and gives new insight into its pathogenic mechanism, diagnosis, and clinical management.

PMID:39722796 | PMC:PMC11668739 | DOI:10.3389/fgene.2024.1477940

Eur J Cell Biol. 2024 Dec 19;104(1):151472. doi: 10.1016/j.ejcb.2024.151472. Online ahead of print.

ABSTRACT

The biliary tract is a ductal network comprising the intrahepatic (IHBDs) and extrahepatic bile duct (EHBDs). Biliary duct disorders include cholangitis, neoplasms, and injury. However, the underlying mechanisms are not fully understood. With advancements in 3D culture technology, cholangiocyte organoids (COs) derived from primary tissues or induced pluripotent stem cells (iPSCs) can accurately replicate the structural and functional properties of biliary tissues. These organoids have become powerful tools for studying the pathogenesis of biliary diseases, such as cystic fibrosis and primary sclerosing cholangitis, and for developing new therapeutic strategies for cholangiocarcinoma. Additionally, COs have the potential to repair bile duct injuries and facilitate transplantation therapies. This review also discusses the use of organoids in genetically engineered mouse models to provide mechanistic insights into tumorigenesis and cancer progression. Continued innovation and standardization of organoid technology are crucial for advancing precision medicine for biliary diseases and cancer.

PMID:39721346 | DOI:10.1016/j.ejcb.2024.151472

Vopr Kurortol Fizioter Lech Fiz Kult. 2024;101(6):40-47. doi: 10.17116/kurort202410106140.

ABSTRACT

OBJECTIVE: To develop and try out a convenient and accessible for use technology for testing the pulmonary function in children and adults, including in patients with chronic bronchopulmonary pathology.

MATERIAL AND METHODS: The article presents the results of Lazarev sound-breathing test (LST) in different cohorts of children and adults, including pregnant women and children suffering from chronic bronchopulmonary diseases, in particular cystic fibrosis.

RESULTS: A direct dependence of the LST indicators' level from the age of children and adolescents has been obtained. An orientational table of age-related changes in the LST indicators in children aged 3-7 years was developed. It has been proven that LST can be used to register the improvement of pulmonary ventilation function in children as a result of specially organized health activities (respiratory gymnastics with elements of respiratory music therapy, etc.). The increase of LST has been obtained with regular exercises on «Sonatal» method (in some cases, the test was increased from 100 to 200%). A direct correlation of LST with hardware diagnostic methods (spirography, peakflowmetry) has been established. The closest links have been established between the LST indicator and vital capacity (VC), peak expiratory flow (PEF), maximum expiratory flow (MEF) at 50% of exhalation (MEF50). In children with low LST values, the correlation coefficient of this indicator with PEF amounted to 0.90, with MEF50 -0.86, with MEF75 - 0.76. The correlation of LST with VC and forced VC was r=0.52 and r=0.45, respectively. Children suffering from cystic fibrosis have shown a decrease of indicators with regard to the indicators of healthy children of the same age. The mean LST values for students aged 17-25 years roughly corresponded to 16-year-old adolescents, indicating that the test values stabilize with the end of body's growth (16-18 years).

CONCLUSION: It has been shown that LST is an accessible and reliable marker for assessing the state of pulmonary ventilation function in healthy and sick children (pre-school and school age) and some cohorts of adults (students, pregnant women), including in health-resort treatment settings.

PMID:39718957 | DOI:10.17116/kurort202410106140

J Exp Zool A Ecol Integr Physiol. 2024 Dec 24. doi: 10.1002/jez.2894. Online ahead of print.

ABSTRACT

In euryhaline teleosts, the cystic fibrosis transmembrane conductance regulator (CFTR) in seawater (SW)-type chloride cells facilitates apical Cl- secretion for SW adaptation, while alternative Cl- excretion pathways remain understudied. This study investigates the role of the calcium-activated chloride channel, Anoctamin 1 (ANO1), in the gills of the euryhaline Japanese medaka (Oryzias latipes) under hyperosmolality and cortisol (CORT) influence. Acclimation to artificial SW, NaCl, mannitol, or glucose significantly upregulated ANO1 and CFTR mRNA expression in gills, unlike urea treatment. In situ hybridization revealed ANO1 mRNA in chloride cells co-expressing CFTR and Na+, K+-ATPase under hyperosmotic conditions. ANO1 inhibition elevated plasma Cl- concentration, indicating impaired Cl- excretion. CORT or dexamethasone administration in freshwater (FW) fish significantly increased branchial ANO1 and CFTR mRNA expression, an effect attenuated by the glucocorticoid receptor (GR) antagonist RU486. Hyperosmotic treatment of isolated gill tissues rapidly induced ANO1 mRNA expression independent of CFTR mRNA changes, and this induction was unaffected by RU486. These findings highlight the dual regulation of ANO1 expression via hyperosmolality-induced cellular response and the CORT-GR system. Thus, branchial ANO1 may likely complement CFTR in Cl⁻ excretion, playing a key role in the hyperosmotic adaptation of euryhaline teleosts.

PMID:39718083 | DOI:10.1002/jez.2894

Am J Physiol Cell Physiol. 2024 Dec 23. doi: 10.1152/ajpcell.00672.2024. Online ahead of print.

ABSTRACT

Pulmonary ionocytes express high levels of cystic fibrosis transmembrane conductance regulator (CFTR) channels. When studied using the short-circuit current technique, ionocytes produce CFTR-dependent short-circuit currents consistent with Cl- secretion. However, when studied without a voltage-clamp, data indicate that ionocytes absorb Cl-. In this review, we resolve these seemingly conflicting findings by considering the different transepithelial voltages and resultant movement of Cl- during short-circuit and physiological open-circuit conditions. This analysis indicates that behavior under short-circuit conditions cannot be directly extrapolated to infer behavior under physiologic conditions. Finally, we discuss the potential role for basolateral Cl- channels in controlling absorption and secretion in ionocytes.

PMID:39716827 | DOI:10.1152/ajpcell.00672.2024

Pharmacotherapy. 2024 Dec 23. doi: 10.1002/phar.4630. Online ahead of print.

ABSTRACT

BACKGROUND: Nutritional support for people with cystic fibrosis (PwCF) after the implementation of novel drug therapies is shifting from managing malnutrition through a high-fat, high-calorie diet to managing emerging incidences of obesity in this population. Additionally, dietary recommendations prescribed with elexacaftor/tezacaftor/ivacaftor (ETI) recommend taking this drug with a fat-containing meal, which is variably interpreted by patients. This pilot and feasibility study was conducted to assess dietary fat intake and body composition on ETI plasma concentrations.

METHODS: Ten participants were enrolled in a 1:1 crossover design by dietary recommendations. To mimic recommendations made during routine clinical care, participants were instructed to consume either a general healthful diet (no more than 30% calories from fat) or a high-fat diet (>40% calories from fat) for a week before crossing over to the alternative diet.

RESULTS: This pilot study was acceptable to and feasible for study participants. Most participants increased fat intake calories when following a high-fat diet. Body composition measurements showed a trending correlation between lean mass and fat-free mass with ETI plasma concentrations. ETI compounds were quantified in plasma at 0 h (prior to the ETI morning dose) and 6 h after ingestion, and consuming a high-fat diet did not significantly impact ETI concentrations.

CONCLUSIONS: Consuming a higher-fat diet did not significantly impact ETI plasma concentrations, and all participants were in range for clinical effectiveness of ETI regardless of fat intake. This work provides vital pilot data to design larger studies to clarify dietary composition for optimal ETI exposure for PwCF on this therapy.

PMID:39716404 | DOI:10.1002/phar.4630

Microbiol Immunol. 2024 Dec 23. doi: 10.1111/1348-0421.13197. Online ahead of print.

ABSTRACT

Antibiotic-resistant pathogens in public settings present a growing risk to human health. Staphylococcus aureus often asymptomatically colonizes human skin, while virulent strains cause soft tissue infections, osteomyelitis, endocarditis, and are associated with cystic fibrosis. Here we investigated the presence and distribution of multidrug-resistant S. aureus on exercise equipment in university recreation facilities. Equipment sampled included barbells (n = 10), dumbbell handles (n = 15), kettle bell handles (n = 5), ellipticals (n = 5), treadmills (n = 5), cable attachments (n = 5). Mannitol salt agar, CHROMagar-MRSA, Gram staining and latex agglutination testing were useds to isolate and identify S. aureus, including methicillin-resistant S. aureus. Kirby-Bauer disc-diffusion assay was utilized to determine antibiotic susceptibility profiles. Results show 42% of 456 S. aureus isolates from 45 different equipment surfaces were ampicillin resistant. Of 60 representative ampicillin-resistant isolates, 92% were resistant to additional antibiotics with the majority resistant to erythromycin (40%) and sulfisoxazole (75%). Multidrug resistance to three or more drugs was observed in 73% of the ampicillin-resistant subpopulation. These results indicate recreational facilities may serve as reservoirs for multi-drug resistant S. aureus including methicillin-resistant S. aureus (MRSA) and regular disinfection of equipment is warranted for safeguarding public health.

PMID:39716386 | DOI:10.1111/1348-0421.13197

J Am Med Inform Assoc. 2024 Dec 23:ocae241. doi: 10.1093/jamia/ocae241. Online ahead of print.

ABSTRACT

OBJECTIVE: We aim to demonstrate the versatility of the All of Us database as an important source of rare and undiagnosed disease (RUD) data, because of its large size and range of data types.

MATERIALS AND METHODS: We searched the public data browser, electronic health record (EHR), and several surveys to investigate the prevalence, mental health, healthcare access, and other data of select RUDs.

RESULTS: Several RUDs have participants in All of Us [eg, 75 of 100 rare infectious diseases (RIDs)]. We generated health-related data for undiagnosed, sickle cell disease (SCD), cystic fibrosis (CF), and infectious (2 diseases) and chronic (4 diseases) disease pools.

CONCLUSION: Our results highlight the potential value of All of Us with both data breadth and depth to help identify possible solutions for shared and disease-specific biomedical and other problems such as healthcare access, thus enhancing diagnosis, treatment, prevention, and support for the RUD community.

PMID:39715481 | DOI:10.1093/jamia/ocae241

PLoS One. 2024 Dec 23;19(12):e0314723. doi: 10.1371/journal.pone.0314723. eCollection 2024.

ABSTRACT

Secretory diarrhea, a major global health concern, particularly among young children, is often characterized by excessive chloride secretion through the cystic fibrosis transmembrane conductance regulator (CFTR) channel. Nornidulin, a fungus-derived natural product from Aspergillus unguis, has previously been shown to inhibit cAMP-induced Cl- secretion in T84 cells (human intestinal cell lines). However, the cellular mechanism of nornidulin in inhibiting cAMP-induced Cl- secretion and its anti-secretory efficacy is still unknown especially in a human colonoid model, a preclinical model recapitulating intestinal physiology in humans. This research study aimed to examine the mechanism of nornidulin to inhibit cAMP-induced chloride secretion and assess its ability to reduce fluid secretion in both T84 cells and human colonoid models. Apical Cl- current analyses showed that nornidulin inhibited CFTR-mediated Cl- current in T84 cells with IC50 of ~1.5 μM. Nornidulin treatment had no effect on CFTR protein expression. Additionally, the inhibitory effects of nornidulin on CFTR-mediated chloride currents were unaffected by the presence of compounds that inhibit negative regulators of CFTR function, such as protein phosphatases, AMP-activated protein kinases, and phosphodiesterases. Interestingly, nornidulin suppressed the increase in intracellular cAMP levels caused by forskolin, an activator of adenylate cyclases, in T84 cells. Using human colonoid models, we found that nornidulin significantly suppressed the forskolin and cholera toxin-induced fluid secretion, indicating that nornidulin exerted an anti-secretory effect in human intestinal epithelia. Collectively, nornidulin represents a novel class of fungus-derived inhibitors of CFTR-mediated Cl- secretion, potentially making it a promising candidate for the development of anti-secretory treatments.

PMID:39715175 | DOI:10.1371/journal.pone.0314723

bioRxiv [Preprint]. 2024 Dec 10:2024.12.09.627592. doi: 10.1101/2024.12.09.627592.

ABSTRACT

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that poses a significant public health threat, particularly in healthcare settings. A key determinant of P. aeruginosa virulence is the regulated synthesis and release of extracellular products, which is controlled by a cell density-dependent signaling system known as quorum sensing (QS). P. aeruginosa uses a complex QS network, including two systems that rely on diffusible N-acylhomoserine lactone (AHL) signal molecules. The LuxR-type receptor RhlR is unique in that it requires not only its cognate AHL but also the accessory protein PqsE to maximally bind to promoter DNA and to initiate transcription. Our group demonstrated that PqsE physically interacts with RhlR, enhancing its affinity for target promoters across the P. aeruginosa genome. Although LuxR-type receptors are widespread in Gram-negative bacteria and important for pathogenesis, PqsE orthologs are restricted to Pseudomonas and Burkholderia species. This study explored the conservation of PqsE and examined PqsE ortholog structure-function across different species. Our results show that PqsE in Pseudomonas retain their functional interactions with RhlR homologs, unlike PqsE orthologs in Burkholderia spp., which do not interact with their respective LuxR-type receptors. Additionally, we assessed the AHL preferences of different receptors and hypothesized that the PqsE-RhlR interaction evolved to stabilize the inherently unstable RhlR, preventing its degradation. Indeed, we observe higher levels of RhlR protein turnover in a strain lacking pqsE compared to WT, which can be rescued in a strain lacking the Lon protease.

IMPORTANCE: Pseudomonas aeruginosa , a major pathogen for patients with cystic fibrosis and a primary constituent of healthcare-associated infections, relies on a complex quorum-sensing (QS) network to coordinate virulence factor production. Central to this system is the interaction between two proteins, PqsE and RhlR, which drive gene expression essential for pathogenesis. Our study investigates the conservation of the PqsE-RhlR interaction across related bacterial species, revealing that PqsE in Pseudomonas can enhance RhlR activity, while orthologs in Burkholderia lack this capacity. These findings offer new insights into the specificity and evolution of QS mechanisms, highlighting the PqsE-RhlR interaction as a potentially selective target for treating P. aeruginosa infections.

PMID:39713373 | PMC:PMC11661239 | DOI:10.1101/2024.12.09.627592

Health Care Transit. 2023 Jul 27;1:100011. doi: 10.1016/j.hctj.2023.100011. eCollection 2023.

ABSTRACT

PURPOSE: Medical advances have increased the life expectancy of adolescents and young adults (AYA) with cystic fibrosis (CF) and importance of high-quality health care transitions (HCT) from pediatric-to-adult focused health care. The purpose of this study was to describe perceptions of HCT readiness among caregivers and AYA with CF during the COVID-19 pandemic.

DESIGN AND METHODS: Using a qualitative descriptive design, caregivers and AYA aged 12-21 years old were recruited from three large CF care centers across the eastern U.S. Data were collected using an online questionnaire with open ended and closed ended questions. Survey topics were: perceptions of HCT readiness, actions to prepare for HCT, and the impact of COVID-19. Results were interpreted using an adapted framework of the Health Care Transition Research Consortium Model and qualitative content analysis.

RESULTS: The sample included 73 caregivers (62 mothers) and 34 AYA (24 female, mean age 15.5 years). Three attributes of HCT readiness were identified from caregiver and AYA perceptions: (1) strong concerns that AYA lacked readiness to manage self-care needs in the future, (2) gaps in resources hindered ongoing efforts to enhance transition readiness, and (3) COVID changes created new barriers and facilitators to health care transition readiness.

CONCLUSIONS: Caregivers and AYA felt they lacked readiness for HCT, they worried about worsening outcomes in adult-focused care, and they were challenged by the onset of the COVID-19 pandemic.

PRACTICAL IMPLICATIONS: These findings provide a solid description of perceived transition readiness during a pandemic that may enhance transitional care design.

PMID:39712998 | PMC:PMC11657345 | DOI:10.1016/j.hctj.2023.100011

Cureus. 2024 Nov 21;16(11):e74157. doi: 10.7759/cureus.74157. eCollection 2024 Nov.

ABSTRACT

Aquagenic syringeal acrokeratoderma (ASA) is a rare dermatological condition characterized by the transient appearance of edematous, white, translucent papules on the palms following water exposure. While the condition is most commonly associated with cystic fibrosis (CF) and predominantly affects young women, this report presents a unique case in a 24-year-old man without a history of cystic fibrosis. The patient reported a 10-month history of painful, pruritic eruptions on the hands following exposure to water. Symptoms resolved within an hour post-exposure but were persistent and increasingly severe over time. The patient's medical history was unremarkable, except for the use of lisinopril for hypertension and propranolol for performance anxiety. Given the absence of CF, the etiology of the disease in this patient remains unclear; however, the use of an angiotensin-converting enzyme (ACE) inhibitor is hypothesized to have contributed to the onset of symptoms through mechanical mechanisms involving sodium retention and osmotic gradient disruption in keratinocytes. This case highlights the diverse clinical presentations and emphasizes the importance of considering ASA in the differential diagnosis of patients without CF or other traditional risk factors. This case underscores the need for further research to elucidate the underlying mechanisms and improve diagnostic accuracy for this rare but potentially debilitating condition.

PMID:39712798 | PMC:PMC11662965 | DOI:10.7759/cureus.74157

Health Care Transit. 2024 Jul 26;2:100065. doi: 10.1016/j.hctj.2024.100065. eCollection 2024.

ABSTRACT

BACKGROUND: Enhancing family readiness for the healthcare transition (HCT) to adult-focused care can help adolescents and young adults (AYA) thrive in adulthood. We aimed to explore modifiable and non-modifiable individual, family, and healthcare factors associated with HCT readiness of AYA among families of AYA with cystic fibrosis (CF) during COVID-19.

METHODS: A multi-site, cross-sectional design was used and an online survey was deployed among families and their AYA from three US pediatric CF centers. The STARx Transition Readiness Questionnaire assessed caregiver- and AYA-perceived HCT readiness of AYA.

RESULTS: Caregivers (N = 71) and their AYA with CF (N = 33, aged 12-21 years) perceived moderately high HCT readiness of AYA. Caregiver resilience was a significant (p = 0.006), family-level factor correlated with caregiver-perceived HCT readiness.

CONCLUSIONS: Families perceived similar levels of AYA readiness for adult-focused care. Caregiver resilience is an important, modifiable family-level factor for targeted interdisciplinary interventions aimed at enhancing HCT processes during COVID-19.

PMID:39712578 | PMC:PMC11658136 | DOI:10.1016/j.hctj.2024.100065

Arch Physiother. 2024 Dec 18;14:131-137. doi: 10.33393/aop.2024.3191. eCollection 2024 Jan-Dec.

ABSTRACT

INTRODUCTION: The modified shuttle test-15 (MST-15) is a valid alternative for assessing exercise capacity when a cardiopulmonary exercise testing is not feasible. This study aims to describe the percentage of healthy and cystic fibrosis (CF) children and adolescents reaching the MST-15 ceiling. Additionally, it examines associations between MST-15 distance and demographic, anthropometric, and lung function data.

METHODS: This retrospective cross-sectional study involved 286 healthy volunteers (11.5 ± 3.3 years) and 70 CF patients (11.9 ± 4.4 years). Data on age, gender, weight, height, body mass index, lung function, and MST-15 were collected. The ceiling effect was determined by the absolute and relative number of participants reaching the 15th level. Univariate linear regression and correlation analyses were conducted to explore associations with MST-15 distance.

RESULTS: A ceiling effect for the MST-15 was found in 19 healthy participants (6.6%) and 1 CF patient (1.4%). The ceiling effect was correlated with age (r = 0.777 for healthy; r = 0.538 for CF), with no cases under 10 years and reaching 25% in healthy participants aged 17-19. Regression analysis showed significant associations between age and MST-15 distance in healthy participants (β = 53.6) and CF patients (β = 32.1). Additionally, sex was significantly associated with MST-15 distance in healthy participants (β = 107.0), and FEV1 with MST-15 distance in CF patients (β = 31.0).

CONCLUSIONS: The ceiling effect on the MST-15 is age-dependent, with no occurrences observed in children under 10 years and a gradual increase in incidence as participants age.

PMID:39711581 | PMC:PMC11659963 | DOI:10.33393/aop.2024.3191

Expert Rev Respir Med. 2024 Dec 22. doi: 10.1080/17476348.2024.2445683. Online ahead of print.

ABSTRACT

INTRODUCTION: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CF transmembrane regulator (CFTR) gene, leading to progressive lung disease and systemic complications. Lung disease remains the primary cause of morbidity and mortality, making early detection of lung function decline crucial. The Lung Clearance Index (LCI), derived from the multiple breath washout (MBW) test, has emerged as a sensitive measure for identifying early airway disease.

AREAS COVERED: This review examines the technical aspects and clinical relevance of LCI, its advantages over traditional lung function tests, and its application in CF clinical trials. A focused literature review highlights LCI's utility in evaluating treatment efficacy and its potential integration into routine CF care.

EXPERT OPINION: LCI is more sensitive than spirometry for detecting early lung function decline and is predominantly used in pediatric settings. Its use is expanding in adult CF populations as advances in treatment allow adults to maintain stable lung function. In clinical trials, LCI is widely recognized as an outcome measure. While implemented into clinical care in many centers in Europe, this is not yet the case in North America. Faster testing protocols and point-of-care interpretation tools will support LCI's integration into routine CF monitoring.

PMID:39709582 | DOI:10.1080/17476348.2024.2445683

Orphanet J Rare Dis. 2024 Dec 20;19(1):482. doi: 10.1186/s13023-024-03506-1.

ABSTRACT

BACKGROUND: Cystic Fibrosis is caused by recessively inherited variants of the cystic fibrosis transmembrane regulator. It is associated with diverse clinical presentations that can affect the respiratory, digestive, and reproductive systems and inhibit nutrient absorption and growth.

MAIN BODY: The current estimation of people affected by Cystic Fibrosis is likely underestimated as this disease remains undiagnosed in countries with limited diagnostic capacity. Recent evidence indicates that Cystic Fibrosis is more common than initially thought and is likely underreported in low- and middle-income countries. The sweat chloride test remains the gold standard for diagnosing Cystic Fibrosis. However, the costs of commercially available instruments, consumables, and laboratory reagents remain relatively high for widespread implementation in low- and middle-income countries.

CONCLUSION: Alternative, cost-effective, and simpler approaches to sweat electrolyte measurement, may present more feasible options for CF diagnosis in the setting of low- and middle-income countries. Novel low-cost, point-of-care innovations for measuring sweat chloride should be explored and further validated as suitable alternatives. It will be important to consider how to implement these options and adjust the diagnostic algorithm to meet the needs of low- and middle-income countries. Future Cystic Fibrosis research in low- and middle-income countries should focus on finding a lower-cost and resource-intensive pathway for CF screening and diagnosis to improve its availability.

PMID:39707455 | DOI:10.1186/s13023-024-03506-1

PLoS One. 2024 Dec 20;19(12):e0314235. doi: 10.1371/journal.pone.0314235. eCollection 2024.

ABSTRACT

BACKGROUND: Lung transplant (LUTX) candidates have subclinical right ventricular (RV) dysfunction, which has not yet been assessed by speckle-tracking echocardiography (STE)-derived RV free-wall longitudinal strain (RVFWLS). To evaluate the prevalence of RV dysfunction by RVFWLS and its relationship with conventional RV echocardiographic indexes in LUTX candidates.

METHODS: In a single-center prospective observational cohort study, from January 2021 to March 2023 consecutive LUTX candidates underwent cardiac catheterization, radionuclide ventriculography, standard and STE. The diagnostic accuracy of RV ejection fraction by ventriculography (RVEF), tricuspid annular plane excursion (TAPSE), fractional area change (FAC), tricuspid peak annulus systolic velocity (S') versus RVFWS were computed.

RESULTS: Thirty-four patients (female, 41%) with a mean age of 48 [36-59] years old enlisted for pulmonary fibrosis (35%) and cystic fibrosis (30%) were included. At cardiac catheterization, only 7 (23%) had pulmonary hypertension. Around 15-25% presented right heart enlargement. Tricuspid regurgitation was present in 20 (60%) of the patients. Median RVFWLS was -20.1% [-22.5%--17%], being impaired (> -20%) in 16 (47%) of the patients. RVFWLS identified the highest percentage (47%) of RV dysfunction, compared to TAPSE (32%), S' (27%), FAC (26%), and ventriculography (15%), which had very low sensitivity for detecting RV dysfunction compared to RVFWLS.

CONCLUSIONS: In patients enlisted for LUTX, RV dysfunction assessed by STE-derived RVFWLS is highly prevalent. STE can detect RV dysfunction better than standard two-dimensional echocardiography and ventriculography. Further studies are urgently needed to define the clinical implications and the prognostic value of RV dysfunction measured with RVFWLS.

PMID:39705303 | DOI:10.1371/journal.pone.0314235

Microbiol Spectr. 2024 Dec 23:e0241524. doi: 10.1128/spectrum.02415-24. Online ahead of print.

ABSTRACT

Mycobacterium abscessus (Mabs) is commonly found in the cystic fibrosis (CF) lung. During infection, Mabs can form biofilms in the lung which reduce both the ability of the immune response to clear infection and the effectiveness of antibiotic therapy. In the CF lung, heme and hemoglobin levels are increased and may provide both iron and heme to Mabs cells. In this work, we show that exogenous heme altered Mabs biofilm formation and measured the effects of exogenous heme on protein level and metabolism in Mabs. Our findings suggest that heme impacts iron homeostasis in Mabs and affects other aspects of its metabolism, highlighting the potential role of heme as a critical nutrient for Mabs growth and biofilm formation.IMPORTANCEMycobacterium abscessus (Mabs) is commonly found in the cystic fibrosis (CF) lung, where Mabs can form biofilms that can reduce the efficacy of antibiotics. During infection, the CF lung can have more than 10 times the extracellular heme than that of a healthy lung. We have found that extracellular heme can change the way Mabs cells grow and form biofilms, which may have implications for pathogenesis.

PMID:39705014 | DOI:10.1128/spectrum.02415-24