BMC Pulm Med. 2024 Jul 1;24(1):307. doi: 10.1186/s12890-024-03114-6.

ABSTRACT

Liver-related side effects are a known complication of treatment with elexacaftor/tezacaftor/ivacaftor (ETI) for cystic fibrosis (CF). Gilbert's syndrome is caused by a genetic mutation that reduces activity of the enzyme UDP glucuronosyltransferase 1 polypeptide A1 (UGT1A1), causing elevated levels of unconjugated bilirubin in the blood and duodenal bile. The presence of Gilbert's syndrome and CF might represent additive risk factors for liver-related adverse events during ETI treatment. This case series describes six people with CF (pwCF) in whom previously unknown Gilbert's syndrome was unmasked after initiation of treatment with ETI. Although all patients had some level of hepatic dysfunction and/or elevated levels of bilirubin after initiation of ETI, the clinical course varied. Only one patient had to stop ETI therapy altogether, while the others were able to continue treatment (some at a reduced dosage and others at the full recommended daily dosage). All patients, even those using a lower dosage, experienced clinical benefit during ETI therapy. Gilbert's syndrome is not a contraindication for ETI therapy but may be mistaken for a risk factor for liver-related adverse events in pwCF. This is something that physicians need to be aware of in pwCF who show liver adverse events during ETI therapy.

PMID:38956524 | DOI:10.1186/s12890-024-03114-6

BMC Pediatr. 2024 Jul 1;24(1):422. doi: 10.1186/s12887-024-04891-z.

ABSTRACT

INTRODUCTION: In highly multiracial populations with inadequate newborn screening, knowledge of the various phenotypic presentations of Cystic Fibrosis (CF) can help reach an early diagnosis. This study aims to describe phenotypes and genotypes at the time of CF diagnosis in a state in the Northeast Region of Brazil.

METHODS: Retrospective cross-sectional study. Clinical data were extracted from the medical records of CF patients. Clinical, laboratory, and genotypic characteristics were described for patients admitted to a tertiary referral center between 2007 and 2021.

RESULTS: Fifty-eight (58) patients were included in the study, 53.5% of whom were diagnosed through clinical suspicion. The median age at diagnosis was 4.7 months (IQR: 1.5-14.8 months). Five patients had false-negative results in the newborn screening. Faltering growth was the most frequent clinical manifestation. Bronchiectasis and a history of pneumonia predominated in those older than ten, while thinness, underweight, and electrolyte imbalances were more frequent in children under two. Sequencing of the CFTR gene identified 27 genotypes, with at least one class I-III variant in all patients, and nine variants that are rare, previously undescribed, or have uncertain significance (619delA, T12991, K162Q, 3195del6, 1678del > T, 124del123bp, 3121-3113 A > T). The most frequent alleles were p.Phe508del, p.Gly542*, p.Arg334Trp, and p.Ser549Arg.

CONCLUSIONS: Malnutrition and electrolyte imbalances were the most frequent phenotypes for children < 2 years and were associated with genotypes including 2 class I-III variants. Rare and previously undescribed variants were identified. The p.Gly542*, p.Arg334Trp, and p.Ser549Arg alleles were among the most frequent variants in this population.

PMID:38956483 | DOI:10.1186/s12887-024-04891-z

Daru. 2024 Jul 2. doi: 10.1007/s40199-024-00526-x. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with cystic fibrosis commonly suffer from lung infections caused by Pseudomonas aeruginosa. Recently, the Levofloxacin (LVF) nebulizing solution (Quinsair®) has been prescribed for the antimicrobial management. The sustained-release (SR) dry powder formulation of LVF is a convenient alternative to Quinsair®. It has the potential to enhance patient convenience and decrease the likelihood of drug resistance over time.

OBJECTIVE: In this paper, we set forth to formulate and evaluate the potential application of sodium alginate (SA) and sodium carboxymethylcellulose (SCMC) for sustained pulmonary delivery of LVF.

METHODS: The spray-dried (SD) LVF microparticles were formulated using SCMC and SA along with L-leucine (Leu). The microparticles were analyzed in terms of particle size, morphology, x-ray diffraction (XRD), in-vitro drug release, and aerodynamic properties. Selected formulations were further proceeded to short-term stability test.

RESULTS: The polymer-containing samples displayed process yield of 33.31%-39.67%, mean entrapment efficiency of 89% and volume size within the range of 2-5 μm. All the hydrogel microparticles were amorphous and exhibited rounded morphology with surface indentations. Formulations with a drug-to-excipient ratio of 50:50 and higher, showed a 24-h SR. The aerodynamic parameters were fine particle fraction and emitted dose percentage ranging between 46.21%-60.6% and 66.67%-87.75%, respectively. The short-term stability test revealed that the formulation with a 50:50 drug-to-excipient ratio, containing SA, demonstrated better physical stability.

CONCLUSION: The selected formulation containing SA has the potential to extend the release duration. However, further enhancements are required to optimize its performance.

PMID:38955893 | DOI:10.1007/s40199-024-00526-x

J Clin Invest. 2024 Jul 2:e176328. doi: 10.1172/JCI176328. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) results from mutations in the CFTR anion channel, ultimately leading to diminished transepithelial anion secretion and mucociliary clearance. CFTR correctors are therapeutics that restore the folding/trafficking of mutated CFTR to the plasma membrane. The BKCa potassium channel is also critical for maintaining lung ASL volume. Here, we show the CFTR corrector, VX-445 (Elexacaftor), a component of Trikafta, induces K+ secretion across WT and F508del CFTR primary human bronchial epithelial cells (HBEs), which was entirely inhibited by the BKCa antagonist paxilline. Similar results were observed with VX-121 - a corrector under clinical evaluation. Whole-cell patch-clamp recordings confirmed potentiated channel activity from CFTR correctors on the BKCa α-subunit, and excised patch-clamp recordings demonstrated a significant increase in open probability. In mesenteric artery, VX-445 induced a paxilline-sensitive vasorelaxation of preconstricted arteries. VX-445 also reduced action potential firing frequency in primary hippocampal and cortical neurons. VX-445 effects were observed at low micomolar concentrations (1-10 µM) - within the range reported in plasma and tissues from CF patients. We raise the possibilities that CFTR correctors gain additional clinical benefit by activation of BKCa in the lung, yet may lead to adverse events through BKCa activation, elsewhere.

PMID:38954478 | DOI:10.1172/JCI176328

Pediatr Nephrol. 2024 Jul 2. doi: 10.1007/s00467-024-06436-z. Online ahead of print.

ABSTRACT

Chronic kidney disease (CKD) encompasses diverse conditions such as congenital anomalies, glomerulonephritis, and hereditary nephropathies, necessitating individualized nutritional interventions. Early detection is pivotal due to the heightened risk of adverse outcomes, including compromised growth and increased healthcare costs. The nutritional assessment in pediatric CKD employs a comprehensive, multidisciplinary approach, considering disease-specific factors, growth metrics, and dietary habits. The prevalence of malnutrition, as identified through diverse tools and guidelines, underscores the necessity for regular and vigilant monitoring. Nutritional management strategies seek equilibrium in calorie intake, protein requirements, and electrolyte considerations. Maintaining a well-balanced nutritional intake is crucial for preventing systemic complications and preserving the remaining kidney function. The nuanced landscape of enteral nutrition, inclusive of gastrostomy placement, warrants consideration in scenarios requiring prolonged support, with an emphasis on minimizing risks for optimized outcomes. In conclusion, the ongoing challenge of managing nutrition in pediatric CKD necessitates continuous assessment and adaptation. This review underscores the significance of tailored dietary approaches, not only to foster growth and prevent complications but also to enhance the overall quality of life for children grappling with CKD.

PMID:38954039 | DOI:10.1007/s00467-024-06436-z

Front Neurol. 2024 Jun 17;15:1388506. doi: 10.3389/fneur.2024.1388506. eCollection 2024.

ABSTRACT

BACKGROUND: Sleep is disturbed in Rett syndrome (RTT), a rare and progressive neurodevelopmental disorder primarily affecting female patients (prevalence 7.1/100,000 female patients) linked to pathogenic variations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene. Autonomic nervous system dysfunction with a predominance of the sympathetic nervous system (SNS) over the parasympathetic nervous system (PSNS) is reported in RTT, along with exercise fatigue and increased sudden death risk. The aim of the present study was to test the feasibility of a continuous 24 h non-invasive home monitoring of the biological vitals (biovitals) by an innovative wearable sensor device in pediatric and adolescent/adult RTT patients.

METHODS: A total of 10 female patients (mean age 18.3 ± 9.4 years, range 4.7-35.5 years) with typical RTT and MECP2 pathogenic variations were enrolled. Clinical severity was assessed by validated scales. Heart rate (HR), respiratory rate (RR), and skin temperature (SkT) were monitored by the YouCare Wearable Medical Device (Accyourate Group SpA, L'Aquila, Italy). The average percentage of maximum HR (HRmax%) was calculated. Heart rate variability (HRV) was expressed by consolidated time-domain and frequency-domain parameters. The HR/LF (low frequency) ratio, indicating SNS activation under dynamic exercise, was calculated. Simultaneous continuous measurement of indoor air quality variables was performed and the patients' contributions to the surrounding water vapor partial pressure [PH2O (pt)] and carbon dioxide [PCO2 (pt)] were indirectly estimated.

RESULTS: Of the 6,559.79 h of biovital recordings, 5051.03 h (77%) were valid for data interpretation. Sleep and wake hours were 9.0 ± 1.1 h and 14.9 ± 1.1 h, respectively. HRmax % [median: 71.86% (interquartile range 61.03-82%)] and HR/LF [median: 3.75 (interquartile range 3.19-5.05)] were elevated, independent from the wake-sleep cycle. The majority of HRV time- and frequency-domain parameters were significantly higher in the pediatric patients (p ≤ 0.031). The HRV HR/LF ratio was associated with phenotype severity, disease progression, clinical sleep disorder, subclinical hypoxia, and electroencephalographic observations of multifocal epileptic activity and general background slowing.

CONCLUSION: Our findings indicate the feasibility of a continuous 24-h non-invasive home monitoring of biovital parameters in RTT. Moreover, for the first time, HRmax% and the HR/LF ratio were identified as potential objective markers of fatigue, illness severity, and disease progression.

PMID:38952469 | PMC:PMC11215834 | DOI:10.3389/fneur.2024.1388506

Lancet. 2024 Jun 28:S0140-6736(24)01134-6. doi: 10.1016/S0140-6736(24)01134-6. Online ahead of print.

NO ABSTRACT

PMID:38950554 | DOI:10.1016/S0140-6736(24)01134-6

Ann Am Thorac Soc. 2024 Jul;21(7):1113. doi: 10.1513/AnnalsATS.21i7Erratum.

NO ABSTRACT

PMID:38949607 | DOI:10.1513/AnnalsATS.21i7Erratum

Ann Am Thorac Soc. 2024 Jul;21(7):1003-1004. doi: 10.1513/AnnalsATS.202404-439ED.

NO ABSTRACT

PMID:38949605 | DOI:10.1513/AnnalsATS.202404-439ED

J Clin Invest. 2024 Jul 1;134(13):e182329. doi: 10.1172/JCI182329.

ABSTRACT

Cystic fibrosis is a debilitating disease characterized by a poor medical prognosis due to devastating lung injury. Recent medical advances targeting the major genetic mutation ΔF508 of the cystic fibrosis transmembrane conductance regulator (CFTR) protein have dramatically increased the lifespan of patients with this mutation. This development has led to major changes in the field and has pushed research beyond the ion transport nature of cystic fibrosis and toward multiorgan physiological reprogramming. In this issue of the JCI, Bae, Kim, and colleagues utilized a large animal pig model prior to the onset of disease. They revealed metabolic reprogramming and organ crosstalk that occurred prior to disease progression. These findings provide paradigm-shifting insight into this complex disease.

PMID:38949023 | DOI:10.1172/JCI182329

bioRxiv [Preprint]. 2024 Jun 22:2024.06.17.599425. doi: 10.1101/2024.06.17.599425.

ABSTRACT

The renin-angiotensin system is a highly characterized integrative pathway in mammalian homeostasis whose clinical spectrum has been expanded to lung disorders such as chronic obstructive pulmonary disease (COPD)-emphysema, idiopathic pulmonary fibrosis (IPF), and COVID pathogenesis. Despite this widespread interest, specific localization of this receptor family in the mammalian lung is limited, partially due to the imprecision of available antibody reagents. In this study, we establish the expression pattern of the two predominant angiotensin receptors in the human lung, AGTR1 and AGTR2 , using complementary and comprehensive bulk and single-cell RNA-sequence datasets that are publicly available. We show these two receptors have distinct localization patterns and developmental trajectories in the human lung, pericytes for AGTR1 and a subtype of alveolar epithelial type 2 cells for AGTR2 . In the context of disease, we further pinpoint AGTR2 localization to the COPD-associated subpopulation of alveolar epithelial type 2 (AT2 B ) and AGTR1 localization to fibroblasts, where their expression is upregulated in individuals with COPD, but not in individuals with IPF. Finally, we examine the genetic variation of the angiotensin receptors, finding AGTR2 associated with lung phenotype (i.e., cystic fibrosis) via rs1403543. Together, our findings provide a critical foundation for delineating this pathway's role in lung homeostasis and constructing rational approaches for targeting specific lung disorders.

PMID:38948835 | PMC:PMC11212981 | DOI:10.1101/2024.06.17.599425

World J Clin Pediatr. 2024 Jun 9;13(2):93341. doi: 10.5409/wjcp.v13.i2.93341. eCollection 2024 Jun 9.

ABSTRACT

BACKGROUND: Fecal calprotectin is a valuable biomarker for assessing intestinal inflammation in pediatric gastrointestinal diseases. However, its role, pros, and cons in various conditions must be comprehensively elucidated.

AIM: To explore the role of fecal calprotectin in pediatric gastrointestinal diseases, including its advantages and limitations.

METHODS: A comprehensive search was conducted on PubMed, PubMed Central, Google Scholar, and other scientific research engines until February 24, 2024. The review included 88 research articles, 56 review articles, six meta-analyses, two systematic reviews, two consensus papers, and two letters to the editors.

RESULTS: Fecal calprotectin is a non-invasive marker for detecting intestinal inflammation and monitoring disease activity in pediatric conditions such as functional gastrointestinal disorders, inflammatory bowel disease, coeliac disease, coronavirus disease 2019-induced gastrointestinal disorders, gastroenteritis, and cystic fibrosis-associated intestinal pathology. However, its lack of specificity and susceptibility to various confounding factors pose challenges in interpretation. Despite these limitations, fecal calprotectin offers significant advantages in diagnosing, monitoring, and managing pediatric gastrointestinal diseases.

CONCLUSION: Fecal calprotectin holds promise as a valuable tool in pediatric gastroenterology, offering insights into disease activity, treatment response, and prognosis. Standardized protocols and guidelines are needed to optimize its clinical utility and mitigate interpretation challenges. Further research is warranted to address the identified limitations and enhance our understanding of fecal calprotectin in pediatric gastrointestinal diseases.

PMID:38948001 | PMC:PMC11212754 | DOI:10.5409/wjcp.v13.i2.93341

Eur Clin Respir J. 2024 Jun 27;11(1):2372901. doi: 10.1080/20018525.2024.2372901. eCollection 2024.

ABSTRACT

BACKGROUND: Bronchiectasis is a disease with predominantly neutrophilic inflammation. As a readily available biomarker, there is little evidence to support the use of blood neutrophil-to-lymphocyte ratio (NLR) to predict bronchiectasis exacerbation severe enough to warrant hospitalization.

METHODS: A registry-based retrospective cohort study was conducted at a in Hong Kong. Chinese patients with non-cystic fibrosis (CF) bronchiectasis were retrospectively reviewed and subsequently followed up to investigate the association of NLR and the need for hospitalization for bronchiectasis exacerbation. Data on the NLR for patients in a clinically stable state in 2018 were collected and patients followed up from 1 January 2019 to 31 December 2022. The primary outcome was the need for hospitalization due to bronchiectasis exacerbation over the next 4 years.

RESULTS: We reviewed 473 Chinese patients with non-CF bronchiectasis, of whom 94 required hospitalization for bronchiectasis exacerbation during the 4-year follow-up period. Multi-variable logistic regression adjusted for E-FACED score (Exacerbation, Forced expiratory volume in 1 s (FEV1), Age, Chronic colonization, Extension, and Dyspnea score), gender, age, smoking status, and presence of co-existing chronic obstructive pulmonary disease (COPD) was conducted to compare patients with highest and lowest quartile NLR. Results revealed that those with NLR at the highest quartile were at increased risk of hospitalization for bronchiectasis exacerbation with an adjusted odds ratio (aOR) of 2.02 (95% confidence interval = 1.00-4.12, p = 0.05).

CONCLUSION: Blood NLR may serve as a marker to predict the need for hospitalization due to bronchiectasis exacerbation.

PMID:38946716 | PMC:PMC11212557 | DOI:10.1080/20018525.2024.2372901

J Pediatr. 2024 Jun 28:114176. doi: 10.1016/j.jpeds.2024.114176. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe reported adverse events (AEs) associated with elexacaftor/tezacaftor/ivacaftor (ETI) in a pediatric sample with cystic fibrosis (CF) aged 6-18 years, with at least one F508del variant, followed at multiple Italian CF centers.

STUDY DESIGN: This was a retrospective, multicenter, observational study. All children receiving ETI therapy from October 2019 to December 2023 were included. We assessed the prevalence and type of any reported potential drug-related AEs, regardless of discontinuation necessity. Persistent AEs were defined as those continuing at the end of the observation period.

RESULTS: Among 608 patients on ETI, 109 (17.9%) reported at least one AE. The majority (N=85, 77.9%) were temporary, with a median duration of 11 days (range 1-441 days). Only 7 (1.1%) patients permanently discontinued treatment, suggesting good overall safety of ETI. The most common AEs leading to discontinuation were transaminase elevations (temporary 14.1%, persistent 25.9%) and urticaria (temporary 41.2%, persistent 7.4%). Creatinine phosphokinase elevation was uncommon. No significant differences in AEs were observed based on sex, age groups (6-11 vs. 12-18 years), or genotype. Pre-existing CF-related liver disease was associated with an increased risk of transaminase elevations. We identified significant variability in the percentage of reported AEs (ANOVA p-value 0·026).

CONCLUSIONS: This real-world study highlights significant variability in reported AEs. Our findings suggest that ETI is a safe and well-tolerated therapy in children and adolescents with CF. However, further long-term safety and effectiveness investigations are warranted.

PMID:38945446 | DOI:10.1016/j.jpeds.2024.114176

Int J Infect Dis. 2024 Jun 28:107125. doi: 10.1016/j.ijid.2024.107125. Online ahead of print.

ABSTRACT

OBJECTIVES: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection (ALRI) in young children. With substantial advances in RSV research, we aimed to conduct an updated systematic review of risk factors for RSV-ALRI in children under five years.

METHODS: We updated our previously published literature search to November 2022 among three English databases and additionally searched three Chinese databases (from January 1995) to identify all relevant publications. We performed random-effects meta-analyses to estimate the pooled odds ratio and 95% confidence interval (CI) for each risk factor and each outcome (RSV-ALRI in the community and RSV-ALRI hospitalisation).

RESULTS: A total of 47 studies were included (26 from the updated search). Indoor air pollution was identified as a possible risk factor for RSV-ALRI in the community (OR 1.45, 95% CI: 1.10-1.90). The identified risk factors for RSV-ALRI hospitalisation fall into four categories: demographic (male sex, Māori and Pacific ethnicities vs European or other ethnicities), pre- and post- neonatal (prematurity, low birth weight, small for gestational age, maternal smoking during pregnancy or lactation, maternal age <30 years vs 30-34 years, multiparity, caesarean section vs vaginal), household and environmental (having siblings, passive smoking, maternal asthma, daycare centre attendance), and health and medical conditions (any chronic diseases, bronchopulmonary dysplasia, HIV infections, congenital heart disease, Down syndrome, cystic fibrosis, previous asthma). The pooled ORs ranged from 1.14 to 4.55.

CONCLUSIONS: Our findings on the risk factors for RSV-ALRI help identify RSV high-risk groups, which has important implications for RSV prevention at both individual and population levels.

PMID:38945430 | DOI:10.1016/j.ijid.2024.107125

J Antimicrob Chemother. 2024 Jun 29:dkae181. doi: 10.1093/jac/dkae181. Online ahead of print.

ABSTRACT

OBJECTIVES: Mycobacterium abscessus has emerged as an opportunistic pathogen responsible for lung infections, especially in cystic fibrosis patients. In spite of the production of the broad-spectrum β-lactamase BlaMab, the carbapenem imipenem is recommended in the initial phase of the treatment of pulmonary infections. Here, we determine whether the addition of vaborbactam, a second-generation β-lactamase inhibitor belonging to the boronate family, improves the activity of β-lactams against M. abscessus.

METHODS: The activity of β-lactams, alone or in combination with vaborbactam, was evaluated against M. abscessus CIP104536 by determining MICs, time-killing and intramacrophage activity. Kinetic parameters for the inhibition of BlaMab by vaborbactam were determined by spectrophotometry.

RESULTS: The combination of vaborbactam (8 mg/L) with β-lactams decreased more than 8 times the MIC of amoxicillin (from >1024 to 128 mg/L) and 2 times the MICs of meropenem (from 16 to 8 mg/L) and imipenem (from 4 to 2 mg/L). The reduction of the MICs was less than that obtained with avibactam at 4 mg/L for amoxicillin (from >1024 to 16 mg/L, more than 64 times less) and for meropenem (from 16 to 4 mg/L, 4 times less). In vitro and intracellularly, M. abscessus was not killed by the meropenem/vaborbactam combination, in spite of significant in vitro inhibition of BlaMab by vaborbactam.

CONCLUSIONS: Inhibition of BlaMab by vaborbactam decreases the MIC of β-lactams, including that of meropenem. As meropenem/vaborbactam is clinically available, this combination offers an alternative therapeutic option that should be evaluated for the treatment of pulmonary infections due to M. abscessus.

PMID:38943535 | DOI:10.1093/jac/dkae181

G Ital Nefrol. 2024 Jun 28;41(3):2024-vol3.

ABSTRACT

Cystic fibrosis is a multisystem disease with extremely variable onset, symptoms and course. One of the onset modality but also a complication of the disease is the pseudo-Bartter syndrome, characterized by hyponatremia, hypochloremic dehydration and metabolic alkalosis in absence of any renal disease. This syndrome occurs more frequently in the first year of life and has a peak in the summer. In this article, we describe two cases of cystic fibrosis associated with pseudo-Bartter syndrome in childhood. Excluding every possible cause of metabolic alkalosis associated with hyponatremia was crucial for our diagnostic pathway, and the experience gained with the first case helped a lot with the second one.

PMID:38943326

BMC Infect Dis. 2024 Jun 28;24(1):650. doi: 10.1186/s12879-024-09541-4.

ABSTRACT

BACKGROUND: Intravenous fosfomycin (IVFOF) is gaining interest in severe infections. Its use may be limited by adverse events (AEs). Little experience exists on IVFOF therapeutic drug monitoring (TDM) in real-life setting.

PATIENTS AND METHODS: Retrospective study of patients receiving IVFOF for > 48 h at Policlinico Hospital (Milan, Italy) from 01/01/2019 to 01/01/2023. AEs associated to IVFOF graded CTCAE ≥ II were considered. Demographic and clinical risk factors for IVFOF-related AEs were analysed with simple and multivariable regression models. The determination of IVFOF TDM was made by a rapid ultraperformance liquid chromatography mass spectrometry method (LC-MS/MS) on plasma samples. The performance of TDM (trough levels (Cmin) in intermittent infusion, steady state levels (Css) in continuous infusion) in predicting AEs ≤ 5 days after its assessment was evaluated.

RESULTS: Two hundred and twenty-four patients were included. At IVFOF initiation, 81/224 (36.2%) patients were in ICU and 35/224 (15.7%) had septic shock. The most frequent infection site was the low respiratory tract (124/224, 55.4%). Ninety-five patients (42.4%) experienced ≥ 1AEs, with median time of 4.0 (2.0-7.0) days from IVFOF initiation. Hypernatremia was the most frequent AE (53/224, 23.7%). Therapy discontinuation due to AEs occurred in 38/224 (17.0%). ICU setting, low respiratory tract infections and septic shock resulted associated with AEs (RRadjusted 1.59 (95%CI:1.09-2.31), 1.46 (95%CI:1.03-2.07) and 1.73 (95%CI:1.27-2.37), respectively), while IVFOF daily dose did not. Of the 68 patients undergone IVFOF TDM, TDM values predicted overall AEs and hypernatremia with AUROC of 0.65 (95%CI:0.44-0.86) and 0.91 (95%CI:0.79-1.0) respectively for Cmin, 0.67 (95%CI:0.39-0.95) and 0.76 (95%CI:0.52-1.0) respectively for Css.

CONCLUSIONS: We provided real world data on the use of IVFOF-based regimens and associated AEs. IVFOF TDM deserves further research as it may represent a valid tool to predict AEs.

KEY POINTS: Real world data on intravenous fosfomycin for severe bacterial infections. AEs occurred in over 40% (therapy discontinuation in 17%) and were related to baseline clinical severity but not to fosfomycin dose. TDM showed promising results in predicting AEs.

PMID:38943088 | DOI:10.1186/s12879-024-09541-4

Sleep Med. 2024 Jun 24;121:77-84. doi: 10.1016/j.sleep.2024.06.023. Online ahead of print.

ABSTRACT

Over the past few years, there has been a surge in interest regarding the connection between sleep duration and quality, sleep disorders, mainly Obstructive sleep apnoea (OSA) and Vitamin D. There is growing evidence to support a new role of Vitamin D in the maintenance and regulation of optimal sleep. Furthermore, a notable link has been identified between OSA and a decrease in serum Vitamin D levels, which appears to intensify as the severity of sleep apnea worsens. Vitamin D status could also potentially serve as a mediator or provide an explanation for the association between OSA and cardiometabolic morbidity, but the current state of research in this area is inadequate. Studies have indicated that the supplementation of Vitamin D can optimize sleep quality, presenting more proof of the connection between insufficient vitamin D levels and sleep disorders. However, it is unclear whether low serum Vitamin D levels are a contributing factor to OSA development or if OSA predisposes individuals to Vitamin D deficiency. As a result, various studies have endeavored to examine the complex relationship between OSA and Vitamin D deficiency. In children and adolescents, while data is limited, there seems also to be a link between sleep disorders and Vitamin D levels. Therefore, the objective of this review is to provide a comprehensive overview of the current evidence on the association between Vitamin D and sleep disorders in both adults and children.

PMID:38941960 | DOI:10.1016/j.sleep.2024.06.023

J Cyst Fibros. 2024 Jun 27:S1569-1993(24)00777-X. doi: 10.1016/j.jcf.2024.06.009. Online ahead of print.

ABSTRACT

BACKGROUND: Adult people living with Cystic Fibrosis (CF) undergo annual screening for CF-related diabetes. These tests represent a burden and can lead to undesirable effects resulting in low adherence. The objectives of this study were to 1) compare gold-standard in-hospital oral glucose tolerance testing (OGTT) with at-home options, and 2) evaluate acceptability of at-home options.

METHODS: A total of 34 adults living with CF undertook 3 types of OGTTs in standardized conditions within two weeks: 1) in a hospital using a 75 g glucose beverage, 2) at home with the same glucose beverage, and 3) at home using a standardized quantity of candy. Glucose levels were measured prior to the OGTT, after 1 and 2 hours. Concordance of glucose measurement, side effects and general appreciation were assessed across the three options.

RESULTS: Mean blood glucose was comparable among the three tests. Glucose tolerance categorization (normal, impaired glucose tolerance, or diabetes) was concordant with the hospital reference test in 59 % of participants for the glucose beverage and 75 % for the candies. Side effects were mild with all types of OGTTs, and 94 % of participants preferred the home options. Among the at-home OGTTs, the glucose beverage was preferred to the candy option.

CONCLUSIONS: Home-based OGTT could be an alternative to gold standard hospital-based OGTT testing, improving adherence to annual testing and reducing costs. However, the discrepancy between various OGTT testing methods could lead to diagnosis dilemma. This approach should be tested on a larger sample size.

PMID:38942723 | DOI:10.1016/j.jcf.2024.06.009