J Cyst Fibros. 2021 Apr 14:S1569-1993(21)00107-7. doi: 10.1016/j.jcf.2021.03.025. Online ahead of print.

ABSTRACT

BACKGROUND: Better insights into the natural course of cystic fibrosis (CF) have led to treatment approaches that have improved pulmonary health and increased the life expectancy of affected individuals. This study evaluated how the combination of modified demographics and changes in CF management impacted resource consumption and the cost of care.

METHODS: Medical records of CF patients from 2006 to 2016 in the French CF Registry were linked to their corresponding claims data (SNDS). Medications, medical visits, procedures, hospitalisations, and indirect costs were annualized by calendar year from 2006 to 2017.

RESULTS: Of the 7,671 patients included in the French CF Registry, 6,187 patients (80.7%) were linked to the SNDS (51.9% male, mean age = 24.7 years). The average cost per patient was €14,174 in 2006, €21,920 in 2011 and €44,585 in 2017. Costs associated with hospital stays increased from €3,843 per patient in 2006 to €6,741 in 2017. In 2017, the mean cost per CF patient was allocated as follows: 72% for medications (of which 51% for modulator therapies), 15% for hospital stays, 7% for medical visits, 3% for indirect costs, 2% for medical devices, 1% for outpatient medical procedures.

CONCLUSION: There was a strong increase in the mean annual cost per CF patient between 2006 and 2017, mostly due to the cost of therapy after the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators. The combination of an increase in the number of CF patients - particularly adult patients - and an increase in the annual cost per patient led to a substantial increase in the total cost of CF disease care for the health systems.

PMID:33865726 | DOI:10.1016/j.jcf.2021.03.025

Sci Rep. 2021 Apr 16;11(1):8336. doi: 10.1038/s41598-021-86069-6.

ABSTRACT

Thoracic dorsal root ganglia (tDRG) contribute to fluid secretion in the upper airways. Inflammation potentiates DRG responses, but the mechanisms remain under investigation. The receptor for advanced glycation end-products (RAGE) underlies potentiation of DRG responses in pain pathologies; however, its role in other sensory modalities is less understood. We hypothesize that RAGE contributes to electrophysiological and biochemical changes in tDRGs during inflammation. We used tDRGs and tracheas from wild types (WT), RAGE knock-out (RAGE-KO), and with the RAGE antagonist FPS-ZM1, and exposed them to lipopolysaccharides (LPS). We studied: capsaicin (CAP)-evoked currents and action potentials (AP), tracheal submucosal gland secretion, RAGE expression and downstream pathways. In WT neurons, LPS increased CAP-evoked currents and AP generation, and it caused submucosal gland hypersecretion in tracheas from WT mice exposed to LPS. In contrast, LPS had no effect on tDRG excitability or gland secretion in RAGE-KO mice or mice treated with FPS-ZM1. LPS upregulated full-length RAGE (encoded by Tv1-RAGE) and downregulated a soluble (sRAGE) splice variant (encoded by MmusRAGEv4) in tDRG neurons. These data suggest that sensitization of tDRG neurons contributes to hypersecretion in the upper airways during inflammation. And at least two RAGE variants may be involved in these effects of LPS.

PMID:33863932 | DOI:10.1038/s41598-021-86069-6

Thorax. 2021 Apr 16:thoraxjnl-2021-216974. doi: 10.1136/thoraxjnl-2021-216974. Online ahead of print.

NO ABSTRACT

PMID:33863830 | DOI:10.1136/thoraxjnl-2021-216974

Arch Pediatr. 2021 Apr 13:S0929-693X(21)00051-8. doi: 10.1016/j.arcped.2021.03.008. Online ahead of print.

ABSTRACT

INTRODUCTION: In France, the cystic fibrosis (CF) care pathway is performed in 45 CF centers, the life expectancy of patients has steadily increased, but to date there are no national recommendations for the transition from pediatric to adult care. The transition to an adult CF center still raises questions about the relevance of its organizational arrangements. The "SAFETIM need" study aimed to identify the organizational needs both of patients and of parents before the transfer to an adult CF center.

METHODS: This was a prospective, observational, multicenter study conducted between July 2017 and December 2018, involving the three CF centers of a regional network in southeastern France. Each adolescent registered with the center and his or her parents were interviewed individually, on the same day, during the 6 months leading up to transfer. They participated in semi-structured interviews during one of their routine consultations at the CF center. The interview manual, based on literature reviews and targeting national recommendations, was tested and validated by the national CF therapeutic education group (GETheM). All interviews were transcribed and checked by two different people, and analyzed by two researchers individually. The results were classified by topic according to content categorization.

RESULTS: Overall, 43 adolescents and 41 parents were interviewed, respectively, who were followed up by CF centers: 14% (n=6) in a mixed CF center (pediatric and adult); 19% (n=8) and 67% (n=29), respectively, in two different pediatric CF centers. Adolescents were between 16 and 19 years old. For adolescents, the average interview time was 5.11min. (standard deviation [SD]: 3.8min; minimum: 2.53min; maximum: 17.14min). For parents, the average interview time was 7.99min (SD: 3.56min, minimum: 3.43min; maximum: 22.50min).

DISCUSSION: Our study enquired only about the preparation and organization of the transfer. We identified three areas of actions matching the needs of adolescents and parents before transfer. The first one is to anticipate team change to prepare follow-up in their future CF center: acquire new skills, consider the future CF center according to the adolescent's curriculum, be involved in the transition process. The second area is to accompany the upcoming change. The care team could help by providing information and support during the start of teenagers' transition toward autonomy. And parents were aware that the CF center change will reverse roles. They must provide their own knowledge and manage the ambivalence of this as well as letting go. The third one is to announce the transition process and functioning of the future adult CF center, because the transition would require time to find their place (patients and parents) with the new team.

CONCLUSION: The "SAFETIM needs" pre-transfer study results show that we can identify the main criteria to be developed and strengthened, to promote a smooth, high-quality transition from pediatric to adult CF care for patients in France. For most patients, the transition cannot be prepared at the last minute. Caregivers need to develop specific skills in adolescent and young adult care and follow-up. Each team must consider the transition as a normal part of the patient care cycle. While it must be structured, some flexibility must be allowed so as to give everyone the chance to be prepared and to personalize the care.

PMID:33863608 | DOI:10.1016/j.arcped.2021.03.008

Int J Pediatr Otorhinolaryngol. 2021 Apr 6;145:110706. doi: 10.1016/j.ijporl.2021.110706. Online ahead of print.

ABSTRACT

PURPOSE: Chronic rhinosinusitis (CRS) is a frequent, quality-of-life (QOL) impairing disease in pediatrics. The SN-5 is a reliable, sensitive and reproductible QOL questionnaire, validated in English for evaluation of CRS disease-specific QOL in children. This study aims to adapt and validate the French version of this test.

METHODS: The SN-5 score was adapted into French language through a forward-backwards translation process, and validated through a monocentric prospective controlled study. Inclusion criteria were 2-12 years of age, CRS symptoms for at least 12 weeks, or absence of sino-nasal symptom for controls. Reproducibility was assessed through Spearman's correlation between initial answers and a re-test conducted 15 days later. Internal consistency was measured through Cronbach's alpha, construct validity through Spearman's correlation between items, discriminative ability through Mann-Whitney tests.

RESULTS: 40 patients and 37 controls filled the score between November 2019 and March 2020. Retest was returned by 35 patients and 35 controls. Mean cases age was 8.5 ± 2.6 years old. 26 patients had primary CRS, 10 had cystic fibrosis, 4 had ciliary dyskinesia. All had diffuse disease. Mean SN-5 overall score was 3.63/7 ± 6.4 for CRS patients and 1.89/7 ± 0.9 for controls (p < 0.001). Test-retest coefficient was 0.84 (0.70-0.92; p < 0.001), Cronbach's alpha was 0.83 for CRS patient. Item per item construct validity was good to excellent.

CONCLUSIONS: The French version of the SN-5 showed good statistical properties, with good test-retest reliability, internal consistency, structural validity and discriminative ability between CRS and control patients.

PMID:33862327 | DOI:10.1016/j.ijporl.2021.110706

PLoS Negl Trop Dis. 2021 Apr 16;15(4):e0009319. doi: 10.1371/journal.pntd.0009319. eCollection 2021 Apr.

ABSTRACT

Trichomonas vaginalis is a common protozoan parasite, which causes trichomoniasis associated with severe adverse reproductive outcomes. However, the underlying pathogenesis has not been fully understood. As the first line of defense against invading pathogens, the vaginal epithelial cells are highly responsive to environmental stimuli and contribute to the formation of the optimal luminal fluid microenvironment. The cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel widely distributed at the apical membrane of epithelial cells, plays a crucial role in mediating the secretion of Cl- and HCO3-. In this study, we investigated the effect of T. vaginalis on vaginal epithelial ion transport elicited by prostaglandin E2 (PGE2), a major prostaglandin in the semen. Luminal administration of PGE2 triggered a remarkable and sustained increase of short-circuit current (ISC) in rat vaginal epithelium, which was mainly due to Cl- and HCO3- secretion mediated by the cAMP-activated CFTR. However, T. vaginalis infection significantly abrogated the ISC response evoked by PGE2, indicating impaired transepithelial anion transport via CFTR. Using a primary cell culture system of rat vaginal epithelium and a human vaginal epithelial cell line, we demonstrated that the expression of CFTR was significantly down-regulated after T. vaginalis infection. In addition, defective Cl- transport function of CFTR was observed in T. vaginalis-infected cells by measuring intracellular Cl- signals. Conclusively, T. vaginalis restrained exogenous PGE2-induced anion secretion through down-regulation of CFTR in vaginal epithelium. These results provide novel insights into the intervention of reproductive complications associated with T. vaginalis infection such as infertility and disequilibrium in vaginal fluid microenvironment.

PMID:33861752 | DOI:10.1371/journal.pntd.0009319

Minerva Pediatr (Torino). 2021 Apr 16. doi: 10.23736/S2724-5276.21.06277-7. Online ahead of print.

NO ABSTRACT

PMID:33861052 | DOI:10.23736/S2724-5276.21.06277-7

Pediatr Pulmonol. 2021 Apr 16. doi: 10.1002/ppul.25431. Online ahead of print.

ABSTRACT

BACKGROUND: Proton pump inhibitors (PPIs) and histamine H2-receptor antagonists (H2RAs) are commonly prescribed to people with CF (PwCF) to treat gastroesophageal reflux disease (GERD) and/or protect pancreatic enzymes from degradation in the stomach. Acid suppressive medications (ASMs) could theoretically reduce hemoglobin (Hgb) levels by restricting enteral iron absorption, but evidence of an association between use of ASMs and lower Hgb levels is lacking in PwCF.

METHODS: We used unadjusted and covariate-adjusted generalized linear mixed models (GLMMs) to estimate the fixed effects of using versus never using ASMs on annual Hgb levels of PwCF in the U.S. CF Foundation Patient Registry from 2011-2017.

RESULTS: There were 9,850 users and 9,007 never-users of ASMs from 2011-2017 who met inclusion criteria. Not adjusting for covariates, Hgb estimates were lower for male and female H2RA and/or PPI users versus never-users. Adjusting for covariates, mean Hgb was 0.1 gm/dl (95% C.I., 0.03, 0.17) lower for males that exclusively used PPIs than it was for male never-users of ASMs (p = 0.008). Adjusting for covariates, mean Hgb levels were 0.11 gm/dl (95% C.I., 0.04, 0.18) lower for females that exclusively used PPIs and 0.16 gm/dl (95% C.I., 0.05, 0.27) lower for females that used PPIs and H2RAs concurrently than it was for female never-users of ASMs (p = 0.005 and p = 0.002 for respective comparisons).

CONCLUSIONS: Males and females with CF who used PPIs and females with CF who concurrently used PPIs and H2RAs had lower Hgb levels than never-users of ASMs of the same sex in the CFFPR from 2011-2017. This article is protected by copyright. All rights reserved.

PMID:33860641 | DOI:10.1002/ppul.25431

Int J Mol Epidemiol Genet. 2021 Feb 15;12(1):1-8. eCollection 2021.

ABSTRACT

Community-acquired pneumonia (CAP) is a leading cause of death in children under five years of age globally. Currently, the vitamin D receptor (VDR) gene is an emerging factor that regulates inflammatory pathways that may alter the response to infections and possibly modify the outcome of CAP. The objective of this study was to investigate the association of VDR gene polymorphisms ApaI, FokI, TaqI, BsmI with CAP in children aged 2-59 months. Hospitalized children aged (2-59 months) with WHO-defined CAP were included as cases after parental consent. Age-matched healthy controls were recruited from the immunization clinic of the hospital within one week of the recruitment of the case. Children with a clinical diagnosis of cystic fibrosis and congenital heart disease were excluded. Four VDR gene polymorphisms, ApaI, FokI, TaqI, BsmI were genotyped by using PCR-RFLP. From Oct-2016 to Oct-2019, 160 cases (34.37% females) and 160 controls (47.5% females) were recruited. Mean age of the cases was 26.30±23.10 months and controls 25.93±15.99 months. In FokI (rs2228570 polymorphism, heterozygous genotype (CT) [OR=2.06, 95% CI=1.25-3.39, P=0.00] and mutant allele (T) [OR=1.45, 95% CI=1.06-2.00, P=0.02] were found to be associated with the risk of CAP. In VDR gene, FokI polymorphism predisposes to CAP in Indian children.

PMID:33859782 | PMC:PMC8044708

Front Physiol. 2021 Mar 30;12:652029. doi: 10.3389/fphys.2021.652029. eCollection 2021.

ABSTRACT

Background: Cystic fibrosis (CF) affects the autonomic nervous system (ANS) and exercise in healthy children modulates the interaction between sympathetic and parasympathetic activity. This study aimed to evaluate the effects of a short-term resistance exercise program on heart rate variability (HRV) in children and adolescents with CF. Methods: A randomized controlled trial was carried out in children diagnosed with CF aged 6-18 years. Individuals were divided into two groups: control (CON) and resistance-training (EX). Individuals in the EX group completed an individualized guided resistance program (5-RM-60-80%) for 8 weeks (3 sessions of 60 min/week). Upper and lower limbs exercises (seated bench press, seated lateral row, and leg press) were used. HRV was measured using a Suunto watch with subjects in lying position. Results: Nineteen subjects (13 boys) were included (CON = 11; and EX = 8). Mean age was 12.2 ± 3.3, FEV1 (forced expiratory volume in the first second) z-score was 1.72 ± 1.54 and peak oxygen consumption (VO2peak) 42.7 ± 7.4 mL.Kg-1.min-1. Exercise induced significant changes in the frequency-domain variables, including a decrease in LF power (p = 0.001, d = 0.98) and LF/HF ratio (p = 0.020, d = 0.92), and an increase in HF power (p = 0.001, d = -0.97), compared to the CON group. No significant changes were found for time-domain variables, although increases with a moderate effect size were seen for SDNN (p = 0.152, d = -0.41) and RMSSD (p = 0.059, d = -0.49) compared to the CON group. Conclusion: A short-term resistance exercise-training program was able to modulate HRV in children and adolescents with CF presenting mild to moderate lung function impairment and good physical condition. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT04293926.

PMID:33859572 | PMC:PMC8042150 | DOI:10.3389/fphys.2021.652029

Front Pharmacol. 2021 Mar 30;12:628722. doi: 10.3389/fphar.2021.628722. eCollection 2021.

ABSTRACT

In cystic fibrosis (CF), defective biogenesis and activity of the cystic fibrosis transmembrane conductance regulator (CFTR) leads to airway dehydration and impaired mucociliary clearance, resulting in chronic airway infection and inflammation. The most common CFTR mutation, F508del, results in a processing defect in which the protein is retained in the endoplasmic reticulum and does not reach the apical surface. CFTR corrector compounds address this processing defect to promote mutant CFTR transfer to the apical membrane. When coupled with potentiators to increase CFTR channel activity, these drugs yield significant clinical benefits in CF patients carrying the F508del mutation. However, processing of CFTR and other proteins can be influenced by environmental factors such as inflammation, and the impact of airway inflammation on pharmacological activity of CFTR correctors is not established. The present study evaluated CFTR-rescuing therapies in inflamed CF airway epithelial cultures, utilizing models that mimic the inflammatory environment of CF airways. Primary bronchial epithelial cultures from F508del/F508del CF patients were inflamed by mucosal exposure to one of two inflammatory stimuli: 1) supernatant from mucopurulent material from CF airways with advanced lung disease, or 2) bronchoalveolar lavage fluid from pediatric CF patients. Cultures inflamed with either stimulus exhibited augmented F508del responses following therapy with correctors VX-809 or VX-661, and overcame the detrimental effects of chronic exposure to the CFTR potentiator VX-770. Remarkably, even the improved CFTR rescue responses resulting from a clinically effective triple therapy (VX-659/VX-661/VX-770) were enhanced by epithelial inflammation. Thus, the airway inflammatory milieu from late- and early-stage CF lung disease improves the efficacy of CFTR modulators, regardless of the combination therapy used. Our findings suggest that pre-clinical evaluation of CFTR corrector therapies should be performed under conditions mimicking the native inflammatory status of CF airways, and altering the inflammatory status of CF airways may change the efficacy of CFTR modulator therapies.

PMID:33859562 | PMC:PMC8042279 | DOI:10.3389/fphar.2021.628722

Thorax. 2021 Apr 15:thoraxjnl-2020-216368. doi: 10.1136/thoraxjnl-2020-216368. Online ahead of print.

ABSTRACT

Diagnosing cystic fibrosis (CF) when sweat chloride is not in the CF range and less than 2 disease-causing CFTR mutations are found requires physiological CFTR assays, which are not always feasible or available. We developed a new physiological CFTR assay based on the morphological differences between rectal organoids from subjects with and without CF. In organoids from 167 subjects with and 22 without CF, two parameters derived from a semi-automated image analysis protocol (rectal organoid morphology analysis, ROMA) fully discriminated CF subjects with two disease-causing mutations from non-CF subjects (p<0.001). ROMA, feasible at all ages, can be centralised to improve standardisation.

PMID:33859053 | DOI:10.1136/thoraxjnl-2020-216368

J Cyst Fibros. 2021 Apr 13:S1569-1993(21)00101-6. doi: 10.1016/j.jcf.2021.03.019. Online ahead of print.

ABSTRACT

The mesenchymal conversion of epithelial cells (EMT) has been suggested as a potential contributor in cystic fibrosis (CF) disease progression. Endothelial cells (EndCs), the cells lining blood vessels, express functional CFTR and CFTR impairment promotes endothelial activation and dysfunction. However, if the mesenchymal switch also exists in CF EndCs remains uncharacterized. To understand whether the endothelial-to-mesenchymal transition (EndMT) could occur in CF, we have conducted a transcriptomic meta-analysis of primary CFTR-impaired and patient-derived EndCs, and further compared our results to data from CF epithelial cells (EpCs) where EMT has been demonstrated. As compared to EpCs, we show that CFTR-impaired EndCs display a limited signature of EndMT, and that expression of the mesenchymal inducer Twist1 remained unchanged. Nonetheless, the use of CFTR modulators reduced the expression of mesenchymal markers from CF patient-derived EndCs, suggesting an additional therapeutic added-value next to the known effect on CFTR ion transport.

PMID:33858770 | DOI:10.1016/j.jcf.2021.03.019

Arch Pediatr. 2021 Apr 12:S0929-693X(21)00050-6. doi: 10.1016/j.arcped.2021.03.006. Online ahead of print.

ABSTRACT

Food oral immunotherapy (OIT) is a promising treatment for persistent and severe food allergies (FAs) in children, but also for accelerating tolerance to cow's milk and cooked egg in young children. In the near future, pediatricians will increasingly encounter severely allergic children undergoing FA-OIT. FA-OIT consists in daily ingestion of increasing doses of the allergen during the up-dosing phase, and ingestion of a constant dose during the maintenance phase. The global aim is to increase the reactive threshold of allergic patients, and finally enable them to ingest a target quantity of allergen without any reaction throughout the treatment (desensitization). Many studies showed the efficacy of FA-OIT in desensitization, and some of them in sustained unresponsiveness. This corresponds to tolerance after FA-OIT discontinuation, especially for cow's milk and hen's egg allergy. However, there is an ongoing debate about the safety of the treatment. Side effects are frequent, notably aversion to the allergen and oral syndromes as well as systemic allergic symptoms. These reactions occur mainly during the up-dosing phase and become less frequent with time, but they are common causes of FA-OIT discontinuation. Patients and their families must be trained to manage these reactions at home. Long-term side effects can also occur, such as eosinophilic esophagitis. Pediatricians play an important role in maintaining patient motivation; they also provide knowledge on possible allergic reactions and the reactogenic cofactors (mainly fever and viral infection, anti-inflammatory intake, physical activity), and refer the patient to the relevant specialists in the case of long-term care. Other routes of administration for food immunotherapy (epicutaneous and sublingual) and different adjuvant treatments (probiotics, anti-IgE molecule) are currently under study. This will allow us to improve the efficacy of immunotherapy and reduce the risk of any side effects, in order to provide a more favorable risk-benefit ratio.

PMID:33858732 | DOI:10.1016/j.arcped.2021.03.006

J Exp Clin Cancer Res. 2021 Apr 15;40(1):133. doi: 10.1186/s13046-021-01939-1.

ABSTRACT

BACKGROUND: Pancreatic stellate cells (PSCs) occupy the majority of the pancreatic cancer microenvironment, contributing to aggressive behavior of pancreatic cancer cells (PCCs). Recently, anti-fibrotic agents have proven to be an effective strategy against cancer, but clinical trials have shown little efficacy, and the driving mechanism remains unknown. N-acetyl-cysteine (NAC) is often used for pulmonary cystic fibrosis. Pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma, was habitually used for type II diabetes, but recently reported to inhibit metastasis of PCCs. However, few studies have focused on the effects of these two agents on cancer-stromal interactions.

METHOD: We evaluated the expression of α-smooth muscle actin (α-SMA) and the number of lipid droplets in PSCs cultured with or without NAC. We also evaluated changes in invasiveness, viability, and oxidative level in PSCs and PCCs after NAC treatment. Using an indirect co-culture system, we investigated changes in viability, invasiveness, and migration of PSCs and PCCs. Combined treatment effects of NAC and Pioglitazone were evaluated in PSCs and PCCs. In vivo, we co-transplanted KPC-derived organoids and PSCs to evaluate the effects of NAC and Pioglitazone's combination therapy on subcutaneous tumor formation and splenic xenografted mouse models.

RESULTS: In vitro, NAC inhibited the viability, invasiveness, and migration of PSCs at a low concentration, but not those of PCCs. NAC treatment significantly reduced oxidative stress level and expression of α-SMA, collagen type I in PSCs, which apparently present a quiescent-like state with a high number of lipid droplets. Co-cultured PSCs and PCCs mutually promoted the viability, invasiveness, and migration of each other. However, these promotion effects were attenuated by NAC treatment. Pioglitazone maintained the NAC-induced quiescent-like state of PSCs, which were reactivated by PCC-supernatant, and enhanced chemosensitivity of PCCs. In vivo, NAC and Pioglitazone's combination suppressed tumor growth and liver metastasis with fewer stromal components and oxidative stress level.

CONCLUSION: NAC suppressed activated PSCs and attenuated cancer-stromal interactions. NAC induces quiescent-like PSCs that were maintained in this state by pioglitazone treatment.

PMID:33858491 | DOI:10.1186/s13046-021-01939-1

Minerva Pediatr (Torino). 2021 Apr 15. doi: 10.23736/S2724-5276.21.06215-7. Online ahead of print.

NO ABSTRACT

PMID:33858133 | DOI:10.23736/S2724-5276.21.06215-7

Minerva Pediatr (Torino). 2021 Apr 15. doi: 10.23736/S2724-5276.21.06189-2. Online ahead of print.

ABSTRACT

OBJECTIVES-AIM: Pulmonary infections are usually caused by bacterial microorganisms such as Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, and Burkholderia cepacia complex in cystic fibrosis (CF) patients. Unusual bacteria (UB) have been described by new isolation techniques recently in the respiratory samples of CF patients. The aim is to investigate the effects of the presence of UB in the respiratory cultures of CF patients on clinical outcomes, necessity of treatment and prognosis.

METHODS: The UB were identified by MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry technology.

RESULTS: Rhizobium radiobacter were detected in 2, Chyrseobacterium species (gleum and indolgenes) in 5, Aeromonas hydrophila in 1, Orchobacterium anthropy in 1,Wautersiella falsenii in 1, Leclercia adecarboxylata in 1, Delftia acidovorans in 1, Cupriavidus Gilardi in 1, R.radiobacter twith Elizabethkingia miricola in 1 and R.radiobacter with C.gleum in 1 patient. Median age of the first UB growth was 3 years. After the first UB growth, the median follow-up time was 15 months. Before the UB growth, 60.0% of the patients had respiratory colonization with methicillin-susceptible S.aureus (MSSA). UB growth were accompanied with MSSA in 66.6% of the patients. Median percentage of FEV1 before and during the UB growth for patients who could perform spirometry, were 80 and 102, respectively. Median body mass index before and during the UB growth were 16 and 16.2, respectively. These UB were not detected during the follow-ups except in one patient.

CONCLUSIONS: The UB growth did not cause any additional symptoms and decrease in BMI and FEV1 in patients with CF. MSSA may be a facilitating factor for UB growth as majority of the patients had MSSA colonization before and during the UB growth.

PMID:33858129 | DOI:10.23736/S2724-5276.21.06189-2

PLoS One. 2021 Apr 15;16(4):e0249695. doi: 10.1371/journal.pone.0249695. eCollection 2021.

ABSTRACT

A major challenge for cell-based non-invasive prenatal testing (NIPT) is to distinguish individual presumptive fetal cells from maternal cells in female pregnancies. We have sought a rapid, robust, versatile, and low-cost next-generation sequencing method to facilitate this process. Toward this goal, single isolated cells underwent whole genome amplification prior to genotyping. Multiple highly polymorphic genomic regions (including HLA-A and HLA-B) with 10-20 very informative single nucleotide polymorphisms (SNPs) within a 200 bp interval were amplified with a modified method based on other publications. To enhance the power of cell identification, approximately 40 Human Identification SNP (Applied Biosystems) test amplicons were also utilized. Using SNP results to compare to sex chromosome data from NGS as a reliable standard, the true positive rate for genotyping was 83.4%, true negative 6.6%, false positive 3.3%, and false negative 6.6%. These results would not be sufficient for clinical diagnosis, but they demonstrate the general validity of the approach and suggest that deeper genotyping of single cells could be completely reliable. A paternal DNA sample is not required using this method. The assay also successfully detected pathogenic variants causing Tay Sachs disease, cystic fibrosis, and hemoglobinopathies in single lymphoblastoid cells, and disease-causing variants in three cell-based NIPT cases. This method could be applicable for any monogenic diagnosis.

PMID:33857205 | DOI:10.1371/journal.pone.0249695

Ann Am Thorac Soc. 2021 Apr 15. doi: 10.1513/AnnalsATS.202009-1214OC. Online ahead of print.

ABSTRACT

Rationale Mycobacterium abscessus is a significant threat to individuals with cystic fibrosis (CF) due to innate drug resistance and potential transmission between patients. Recent studies described global dominant circulating clones of M. abscessus, but detailed genomic surveys have not yet been described for the United States (US). Objectives We examined the genetic diversity of respiratory M. abscessus isolates from US patients with CF and evaluated the potential for transmission events within CF Care Centers. Methods Whole genome sequencing was performed on 558 M. abscessus isolates from 266 patients with CF attending 48 CF Care Centers in 28 US states as part of a nationwide surveillance program. US isolates were also compared to 64 isolate genomes from 13 previous studies to evaluate the prevalence of recently described dominant circulating clones. Results More than half of study patients with CF and M. abscessus had isolates within four dominant clones; two clones of M. abscessus subsp. abscessus (MAB) and two clones of M. abscessus subsp. massiliense (MMAS). Acquired drug resistance mutations for aminoglycosides and macrolides were rare in the isolate population, and they were not significantly enriched in dominant clones compared to unclustered isolates. For a subset of 55 patients, there was no relationship between dominant clones and diagnosis of active lung disease (p=1.0). Twenty-nine clusters of genetically similar MAB isolates and eight clusters of genetically similar MMAS isolates were identified. Overall, 28/204 (14%) patients with MAB and 15/64 (23%) with MMAS had genetically similar isolates to at least one other patient at the same CF Care Center. Genetically similar isolates were also found between 60/204 (29%) patients with MAB and 19/64 (30%) with MMAS from different geographic locations. Conclusions Our study reveals the predominant genotypes of M. abscessus and frequency of shared strains between patients in US CF Care Centers. Integrated epidemiological and environmental studies would help to explain the widespread presence of dominant clones in the US, including the potential for broad distribution in the environment. Single site studies using systematic, evidence-based approaches will be needed to establish the contributions of healthcare-associated transmission versus shared environmental exposures.

PMID:33856965 | DOI:10.1513/AnnalsATS.202009-1214OC

J Paediatr Child Health. 2021 Apr 15. doi: 10.1111/jpc.15495. Online ahead of print.

NO ABSTRACT

PMID:33856079 | DOI:10.1111/jpc.15495