Ann Am Thorac Soc. 2022 Nov 21. doi: 10.1513/AnnalsATS.202201-024OC. Online ahead of print.

ABSTRACT

RATIONALE: Variants within the cystic fibrosis transmembrane conductance regulator gene (CFTR) that are of unknown significance or are categorized as non CF-causing may be observed in persons with CF. These variants are frequently detected in children with inconclusive newborn screen results and, in some cases, may be associated with a benign presentation in early childhood that progresses to a CF phenotype later in life.

OBJECTIVES: To analyze data from individuals enrolled in the U.S. CF Foundation patient registry who have received a diagnosis of CF and who have variants found in a population of children with cystic fibrosis screen positive, inconclusive diagnosis (CFSPID).

METHODS: This retrospective review analyzed registry data from individuals with a diagnosis of CF who also harbor one or more variants of interest due to their frequency within a CFSPID population and/or their interpretation as non CF-causing. Three groups were defined by the number of CF-causing (CF-C) variants identified (CF-Cx2, CF-Cx1, and CF-Cx0), which were reported in addition to variant(s) of interest. Multivariate quantile regression modeling of FEV1 outcome generated a disease severity score for each person determined by six selected variables. Median scores were calculated for the three groups.

RESULTS: Patients carrying one CF-causing variant and at least one variant of interest (CF-Cx1) had higher median disease severity score compared to CF-Cx2, suggesting milder phonotype (p<0.05). However, there was no statistically significant difference in scores between CF-Cx2 and the two other groups combined (CF-Cx1 and CF-Cx0; p=0.33). Analysis revealed that the CF-Cx1 and CF-Cx0 groups, when compared to the CF-Cx2 group, had later median diagnoses (8 years vs. newborn; p<0.0001), lower median sweat chloride (48 vs. 94.5 mmol/L, p<0.0001), lower prevalence of pancreatic insufficiency (29% vs. 78%; p<0.0001), and higher median FEV1% predicted (95% vs. 87%; p=0.0002).

CONCLUSIONS: Individuals with CF who have specific variants frequently identified in children with CFSPID have a similar range of disease severity scores compared to those who have two CF-causing variants, but a milder phenotype overall. Variants that should be given careful scrutiny due to their high prevalence are: G576A+R668C, T854T, R75Q, F1052V, R1070W, R31C, and L967S.

PMID:36409994 | DOI:10.1513/AnnalsATS.202201-024OC

Expert Opin Biol Ther. 2022 Nov 21. doi: 10.1080/14712598.2022.2150544. Online ahead of print.

ABSTRACT

BACKGROUND: Airway gene therapy could produce lasting benefit for cystic fibrosis (CF) lung disease, however patient and public support is critical for successful adoption. This project aimed to examine perceptions towards gene therapy for CF.

RESEARCH DESIGN AND METHODS: Two separate quantitative online surveys were conducted to examine perceptions towards airway gene therapy for CF among people with CF, their families, and members of the public. Data was collected from a total of 213 participants across both studies, with 43 having a diagnosis of CF, 122 having a family member with CF, and 135 knowing someone with CF.

RESULTS: Participants in both studies displayed positive perceptions towards gene therapy and were supportive of involvement in CF gene therapy trials. Around 50% hoped gene therapy could provide a cure. In Study 1 gene therapy was the most important research area, but in Study 2 this was new daily drugs. Almost all thought gene therapy was still required even if modulators already improved quality of life.

CONCLUSION: The factors that influence acceptance, whether trials would be positively viewed, and whether individuals with CF are receptive to gene therapy, are essential to determine prior to clinical trials. Our findings indicate people have positive opinions about airway gene therapy for CF, but further education is vital.

PMID:36408943 | DOI:10.1080/14712598.2022.2150544

J Clin Tuberc Other Mycobact Dis. 2022 Nov 13;29:100339. doi: 10.1016/j.jctube.2022.100339. eCollection 2022 Dec.

ABSTRACT

Bronchiectasis are abnormal permanently dilated bronchi which lead to chronic cough and other respiratory symptoms. Though tuberculosis (TB) is a common cause of bronchiectasis, data on this association are scarce. The objective of this study was to describe the profile of patients with post-TB bronchiectasis at a tertiary hospital in the southern region of Brazil. This was a retrospective study with data from patients in follow-up at our hospital from January 2005 to December 2020. We included patients 14 years of age or older who had bronchiectasis on chest computed tomography and a history of pulmonary TB. We excluded patients with bronchiectasis due to other causes or with confirmed non-tuberculous mycobacteria infection. We included 54 of the 204 non-cystic fibrosis bronchiectasis patients seen at our hospital during the study period. Most of the patients were female, older, and non-smokers. Less than a third had chronic bronchial infection by some agent. More than two thirds had some type of ventilatory defect, the most common being obstruction. More than half had upper-lobe impairment. Severity of the disease seemed to be equally distributed from mild to severe. Treatment was varied, including bronchodilators, inhaled corticosteroids, and azithromycin. We found that the profile of patients in our hospital is similar to that described in other studies, with slight differences in regard to microbiology and treatment.

PMID:36405996 | PMC:PMC9672944 | DOI:10.1016/j.jctube.2022.100339

Dig Liver Dis. 2022 Nov 17:S1590-8658(22)00780-0. doi: 10.1016/j.dld.2022.10.024. Online ahead of print.

ABSTRACT

BACKGROUND: Proton pump inhibitors (PPIs) are widely prescribed in all age groups, and their use is increasing. However, their safety profile has been frequently questioned.

AIMS: The aim of this study was to analyze the characteristics of PPI-related adverse drug reactions (ADRs) reported to the Italian spontaneous reporting system (SRS) database and relative to an Italian region (Sicily).

METHODS: A 20-year observational, retrospective study was conducted, evaluating PPI-related ADR reports from Sicily between January 1st, 2001, and June 30th, 2021. The factors associated with ADR seriousness were investigated.

RESULTS: A total of 148 spontaneous reports of ADRs related to PPIs were analyzed. Lansoprazole was the drug with the highest number of associated reports (30.87%). The most frequently reported ADRs were cutaneous (24.56%) and/or gastrointestinal manifestations (18.10%), the latter especially in the case of lansoprazole-related ADRs (p<0.006). The great majority of ADR reports were relative to on-label prescriptions. Serious ADRs were 39 (26.35%). Serious ADRs were more common in reports including omeprazole than in reports containing other PPIs (p<0.008) and in reports presenting PPIs combined with other drugs than in reports with PPI single therapies (p<0.001).

CONCLUSION: Most PPI-related ADRs are non-serious. Omeprazole and combination therapy seem to be associated with ADR seriousness.

PMID:36404233 | DOI:10.1016/j.dld.2022.10.024

BMC Endocr Disord. 2022 Nov 18;22(1):283. doi: 10.1186/s12902-022-01191-4.

ABSTRACT

BACKGROUND: People living with type 1 diabetes (PWT1D) are at increased risk for impairments in brain function, which may impact on daily life. Cognitive impairments in PWT1D might contribute to increasing eating disorders, reducing self-management skills, and deteriorating glycemic control. Glycemic variability may be a key determinant of disordered eating behaviors, as well as of cognitive impairments. The main objective of this study is to better understand the impact of glycemic variability in disordered eating behaviors and cognitive impairment, and its consequences on self-management skills in PWT1D.

METHOD: We aim to recruit 150 PWT1D with 50% of men and women in this cross-sectional study. Participants will record their glycemic variability over a 10-day period using a continuous glucose monitoring system (CGMS) and track their dietary intakes using image-assisted food tracking mobile application (2 days). Over four online visits, eating behaviors, diabetes self-management's skills, anxiety disorders, depression disorder, diabetes literacy and numeracy skills, cognitive flexibility, attention deficit, level of interoception, and impulsivity behaviors will be assessed using self-reported questionnaires. Cognitive functions (i.e., attention, executive functions, impulsivity, inhibition and temporal discounting), will be measured. Finally, medical, biological and sociodemographic data will be collected. To further our understanding of the PWT1D experience and factors impacting glycemic self-management, 50 PWT1D will also participate in the qualitative phase of the protocol which consist of individual in-depth face-to-face (virtual) interviews, led by a trained investigator using a semi-structured interview.

DISCUSSION: This study will contribute to highlighting the consequences of blood sugar fluctuations (i.e., "sugar swings"), in daily life, especially how they disrupt eating behaviors and brain functioning. A better understanding of the mechanisms involved could eventually allow for early detection and management of these problems. Our study will also seek to understand the patients' point of view, which will allow the design of appropriate and meaningful recommendations.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT05487534. Registered 4 August 2022.

PMID:36401237 | PMC:PMC9673316 | DOI:10.1186/s12902-022-01191-4

Respir Res. 2022 Nov 19;23(1):317. doi: 10.1186/s12931-022-02229-w.

ABSTRACT

BACKGROUND: Emerging experimental and epidemiological evidence highlights a crucial cross-talk between the intestinal flora and the lungs, termed the "gut-lung axis". However, the function of the gut microbiota in bronchiectasis remains undefined. In this study, we aimed to perform a multi-omics-based approach to identify the gut microbiome and metabolic profiles in patients with bronchiectasis.

METHODS: Fecal samples collected from non-CF bronchiectasis patients (BE group, n = 61) and healthy volunteers (HC group, n = 37) were analyzed by 16 S ribosomal RNA (rRNA) sequencing. The BE group was divided into two groups based on their clinical status: acute exacerbation (AE group, n = 31) and stable phase (SP group, n = 30). Further, metabolome (lipid chromatography-mass spectrometry, LC-MS) analyses were conducted in randomly selected patients (n = 29) and healthy volunteers (n = 31).

RESULTS: Decreased fecal microbial diversity and differential microbial and metabolic compositions were observed in bronchiectasis patients. Correlation analyses indicated associations between the differential genera and clinical parameters such as bronchiectasis severity index (BSI). Disease-associated gut microbiota was screened out, with eight genera exhibited high accuracy in distinguishing SP patients from HCs in the discovery cohort and validation cohort using a random forest model. Further correlation networks were applied to illustrate the relations connecting disease-associated genera and metabolites.

CONCLUSION: The study uncovered the relationships among the decreased fecal microbial diversity, differential microbial and metabolic compositions in bronchiectasis patients by performing a multi-omics-based approach. It is the first study to characterize the gut microbiome and metabolome in bronchiectasis, and to uncover the gut microbiota's potentiality as biomarkers for bronchiectasis.

TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, number NCT04490447.

PMID:36403022 | DOI:10.1186/s12931-022-02229-w

J Cyst Fibros. 2022 Nov 16:S1569-1993(22)01411-4. doi: 10.1016/j.jcf.2022.11.002. Online ahead of print.

ABSTRACT

BACKGROUND: Regular participation in physical activity (PA) is encouraged for people with Cystic Fibrosis (CF). This study aimed to assess the effectiveness of an intervention using wearable technology, goal setting and text message feedback on PA and health outcomes in people with CF.

METHODS: This was a pilot randomised trial conducted at University Hospital Limerick. Participants were randomly assigned to the intervention (INT) or active comparator (AC). The 12-week intervention consisted of wearable technology (Fitbit Charge 2) which was remotely monitored, and participants set step count goals. Participants were sent a one-way text message once a week over 12 weeks to positively reinforce and encourage PA participation. The AC group received the wearable technology alone. Follow up was assessed at 24 weeks. Outcomes assessed were PA, aerobic capacity, lung function, sleep, quality of life and wellbeing.

RESULTS: Step count increased significantly for the INT group over 12 weeks when compared to the AC group (p=0.019). The INT group had a 28% week-to-week percentage change (Weeks 1-12), while the AC group reduced by 1%, p=0.023. Within group changes demonstrated that VO2 peak (ml/kg/min) significantly increased for the INT group at 12 weeks (24.4 ±7.65 to 26.13 ±7.79, p=0.003) but not at 24 weeks (24.45 ±7.05, p=0.776). There were no significant differences observed for VO2 peak (ml/kg/min) for the AC group. There was no significant effect on lung function, sleep, well-being, or quality of life for either group.

CONCLUSIONS: A personalised PA intervention using wearable technology, goal setting and text message feedback increased PA and aerobic capacity in people with CF. Integration of this intervention into usual care may encourage regular PA participation for people with CF.

PMID:36402730 | DOI:10.1016/j.jcf.2022.11.002

J Cyst Fibros. 2022 Nov 16:S1569-1993(22)01412-6. doi: 10.1016/j.jcf.2022.11.003. Online ahead of print.

ABSTRACT

BACKGROUND: With the increasing availability of highly effective modulators for people living with cystic fibrosis (CF), there is a need to re-design research studies to reflect the changing epidemiology of the CF population. The lung clearance index (LCI), a sensitive physiological measure of lung function, may be ideally suited as an endpoint in the era of CF modulator therapies. In this study we describe study design considerations for implementing LCI into interventional and observational research.

METHODS: Simulations were used to estimate the required sample size to detect a range of treatment effects for interventional studies (including cross-over trials) and to track lung disease progression in observational studies.

RESULTS: Using published treatment effects to inform the design of prospective studies can lead to inefficient study designs. Large improvements in LCI for a few individuals can skew results and can influence interpretations of treatment effects. Adjusting for baseline LCI can help to improve the efficiency of a study. Compared to the forced expiratory volume in 1 second (FEV1), analysis using LCI as an endpoint requires as little as one third of the total sample size.

CONCLUSIONS: Planning of prospective studies that include LCI as an endpoint need to consider baseline LCI and disease severity of the study population; whereas interpretation of results needs to consider whether a few individuals skew the overall treatment effect.

PMID:36402729 | DOI:10.1016/j.jcf.2022.11.003

Paediatr Respir Rev. 2022 Aug 23:S1526-0542(22)00050-1. doi: 10.1016/j.prrv.2022.08.001. Online ahead of print.

NO ABSTRACT

PMID:36402662 | DOI:10.1016/j.prrv.2022.08.001

Lancet Respir Med. 2022 Nov 16:S2213-2600(22)00447-7. doi: 10.1016/S2213-2600(22)00447-7. Online ahead of print.

NO ABSTRACT

PMID:36402149 | DOI:10.1016/S2213-2600(22)00447-7

Arch Bronconeumol. 2022 Nov 5:S0300-2896(22)00599-3. doi: 10.1016/j.arbres.2022.10.011. Online ahead of print.

NO ABSTRACT

PMID:36400654 | DOI:10.1016/j.arbres.2022.10.011

Thorax. 2022 Nov 18:thorax-2022-219600. doi: 10.1136/thorax-2022-219600. Online ahead of print.

NO ABSTRACT

PMID:36400456 | DOI:10.1136/thorax-2022-219600

PLoS One. 2022 Nov 18;17(11):e0277096. doi: 10.1371/journal.pone.0277096. eCollection 2022.

ABSTRACT

Vasoactive intestinal peptide (VIP) as a neurocrine factor released by enteric neurons has been postulated to participate in the regulation of transcellular active calcium transport across intestinal epithelium, but the preceding evidence is scant and inconclusive. Herein, transepithelial calcium flux and epithelial electrical parameters were determined by Ussing chamber technique with radioactive tracer in the intestinal epithelium-like Caco-2 monolayer grown on Snapwell. After 3-day culture, Caco-2 cells expressed mRNA of calcium transporters, i.e., TRPV6, calbindin-D9k, PMCA1b and NCX1, and exhibited transepithelial resistance of ~200 Ω cm2, a characteristic of leaky epithelium similar to the small intestine. VIP receptor agonist was able to enhance transcellular calcium flux, whereas VIP receptor antagonist totally abolished calcium fluxes induced by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Since the intestinal cystic fibrosis transmembrane conductance regulator (CFTR) could be activated by VIP and calciotropic hormones, particularly parathyroid hormone, we sought to determine whether CFTR also contributed to the 1,25(OH)2D3-induced calcium transport. A selective CFTR inhibitor (20-200 μM CFTRinh-172) appeared to diminish calcium fluxes as well as transepithelial potential difference and short-circuit current, both of which indicated a decrease in electrogenic ion transport. On the other hand, 50 μM genistein-a molecule that could rapidly activate CFTR-was found to increase calcium transport. Our in silico molecular docking analysis confirmed direct binding of CFTRinh-172 and genistein to CFTR channels. In conclusion, VIP and CFTR apparently contributed to the intestinal calcium transport, especially in the presence of 1,25(OH)2D3, thereby supporting the existence of the neurocrine control of intestinal calcium absorption.

PMID:36399482 | DOI:10.1371/journal.pone.0277096

Am J Transl Res. 2022 Oct 15;14(10):7612-7620. eCollection 2022.

ABSTRACT

We report a rare case of a patient with cystic fibrosis suffering from debilitating abdominal pain due to chronic pancreatitis. This 13-year-old patient was evaluated for surgical intervention to relieve pain from chronic pancreatitis and to improve quality of life. The patient carried two mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; the most common ΔF508 variant and a second variant, p.Glu1044Gly, which has not been previously described. The patient's condition did not improve despite medical management and multiple endoscopic interventions, and therefore total pancreatectomy with islet autotransplantation and a near-total duodenectomy was offered for definitive management. Patient-derived duodenal crypts were isolated and cultured from the resected duodenum, and duodenal organoids were generated to test CFTR function. Our studies demonstrate that this novel mutation (ΔF508/p.Glu1044Gly) caused severely impaired CFTR function in vitro. The Food and Drug Administration (FDA)-approved drug ivacaftor, a CFTR potentiator, was identified to robustly improve CFTR function in the context of this novel mutation. Herein, we describe a personalized medicine approach consisting of performing drug testing on individual patient derived organoids that has potential to guide management of patients with novel CFTR genetic mutations. Identified effective medical therapeutics using this approach may avoid irreversible surgical treatments such as total pancreatectomy with islet autotransplantation in the future.

PMID:36398272 | PMC:PMC9641468

JBMR Plus. 2022 Sep 16;6(11):e10666. doi: 10.1002/jbm4.10666. eCollection 2022 Nov.

ABSTRACT

Single-center studies have suggested that up to 70% of adults with cystic fibrosis (CF) have lower than expected bone mineral density (BMD), substantially higher than the 25% prevalence reported from national registries. We determined the prevalence of low BMD in CF adults at our center and assessed risk factors for low BMD. This retrospective cohort study was conducted in all CF patients ≥18 years of age who had a dual-energy X-ray absorptiometry (DXA) scan performed at the Johns Hopkins Adult Cystic Fibrosis center between 2010 and 2018. Prevalence and incidence of low BMD during the study period were determined. Poisson regression based on generalized estimating equations and robust standard errors were used to evaluate selected risk factors and risk of disease progression. A total of 234 individuals underwent an initial DXA scan. At this scan, prevalence of low BMD was 52.6% (95% confidence interval [CI] 46.0-59.1). A total of 43.6% were at risk for CF-related low BMD (AR-CFLBMD) (95% CI 37.1-50.2) and 9.0% had CF-related low BMD (CFRLBMD) (95% CI 5.6-13.4). Of the 25 with normal BMD at initial scan and a subsequent follow-up scan, 8 (32.0%) progressed to AR-CFLBMD. Of the 53 with AR-CFLBMD on initial scan and a subsequent scan, 6 (11.3%) progressed to CFLBMD, 9 (17.0%) returned to normal BMD, and 38 (71.7%) remained AR-CFLBMD. Older age (relative risk [RR] = 1.01; 95% CI 1.00-1.01) and male sex (RR = 1.32; 95% CI 1.04-1.66) were associated with increased risk of low BMD, while higher forced expiratory volume over 1 second (FEV1%) predicted (RR = 0.99; 95% CI 0.99-1.00) and body mass index (BMI; RR = 0.97; 95% CI 0.94-1.00) were associated with lower risk for low BMD. The fact that more than half of all individuals were found to have lower than expected BMD suggests that the actual prevalence may be higher than currently reported in national registries. This supports the importance of universal bone health screening of all CF adults. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

PMID:36398108 | PMC:PMC9664525 | DOI:10.1002/jbm4.10666

BMC Pulm Med. 2022 Nov 17;22(1):424. doi: 10.1186/s12890-022-02233-2.

ABSTRACT

BACKGROUND: Massive hemoptysis is a rare but potentially life-threatening condition of patients with cystic fibrosis (CF) and advanced pulmonary disease. Hypertrophied bronchial arteries are understood to cause massive hemoptysis when rupturing. Risk factors to predict massive hemoptysis are scarce and bronchial artery diameters are not part of any scoring system in follow-up of patients with CF. Aim of this study was to correlate bronchial artery diameter with massive hemoptysis in CF.

METHODS: Bronchial artery and non-bronchial systemic artery diameters were measured in contrast enhanced computed tomography (CT) scans in patients with massive hemoptysis and compared to patients with end-stage CF and no history of hemoptysis. Demographic and clinical data and side of bronchial artery/non-bronchial systemic artery hypertrophy and coil embolization were documented.

RESULTS: In this retrospective multicenter study 33 patients with massive hemoptysis were included for bronchial artery/non-bronchial systemic artery diameter measurements, (13 female, 20 male, median age 30 years (18-55)). Bronchial artery diameters were significantly larger in the case group than in the control group with median 4 mm (2.2-8.2 mm), and median 3 mm (1-7 mm), respectively (p = 0.002). Sensitivity of bronchial arteries ≥ 3.5 mm to be associated with hemoptysis was 0.76 and specificity 0.71 with ROC creating an area under the curve of 0.719. If non-bronchial systemic arteries were present, they were considered culprit and embolized in 92% of cases.

CONCLUSION: Bronchial arteries ≥ 3.5 mm and presence of hypertrophied non-bronchial systemic arteries correlate with massive hemoptysis in patients with CF and might serve as risk predictor for massive hemoptysis. Therefore, in patients with advanced CF we propose CT scans to be carried out as CT angiography to search for bronchial arteries ≥ 3.5 mm and for hypertrophied non-bronchial systemic arteries as possible risk factors for massive hemoptysis.

PMID:36397043 | DOI:10.1186/s12890-022-02233-2

Sci Rep. 2022 Nov 17;12(1):19748. doi: 10.1038/s41598-022-24374-4.

ABSTRACT

Survival statistics, estimated using data from national cystic fibrosis (CF) registries, inform the CF community and monitor disease progression. This study aimed to estimate survival among people with CF in Australia and to identify factors associated with survival. This population-based cohort study used prospectively collected data from 23 Australian CF centres participating in the Australian CF Data Registry (ACFDR) from 2005-2020. Period survival analysis was used to calculate median age of survival estimates for each 5-year window from 2005-2009 until 2016-2020. The overall median survival was estimated using the Kaplan-Meier method. Between 2005-2020 the ACFDR followed 4,601 people with CF, noting 516 (11.2%) deaths including 195 following lung transplantation. Out of the total sample, more than half (52.5%) were male and 395 (8.6%) had undergone lung transplantation. Two thirds of people with CF (66.1%) were diagnosed before six weeks of age or by newborn/prenatal screening. The overall median age of survival was estimated as 54.0 years (95% CI: 51.0-57.04). Estimated median survival increased from 48.9 years (95% CI: 44.7-53.5) for people with CF born in 2005-2009, to 56.3 years (95% CI: 51.2-60.4) for those born in 2016-2020. Factors independently associated with reduced survival include receiving a lung transplant, having low FEV1pp and BMI. Median survival estimates are increasing in CF in Australia. This likely reflects multiple factors, including newborn screening, improvement in diagnosis, refinements in CF management and centre-based multidisciplinary care.

PMID:36396972 | DOI:10.1038/s41598-022-24374-4

Microbiol Spectr. 2022 Nov 17:e0247122. doi: 10.1128/spectrum.02471-22. Online ahead of print.

ABSTRACT

Both Pseudomonas aeruginosa and Mycobacterium abscessus are bacteria that cause pulmonary infection in people with inflammatory lung disease, including individuals with cystic fibrosis (CF). These bacterial species inhabit the same environmental reservoirs (soil and water) and can be coisolated in the lungs of people with CF. We investigated the interaction of these bacteria and found an antagonistic interaction favoring P. aeruginosa that was observed in biofilms but not in planktonic cultures. This antagonism extended to multiple P. aeruginosa strains and against Mycobacterium smegmatis. We tested known P. aeruginosa mutants for genes that can play roles in interbacterial contact-dependent (type III and type VI secretion systems) and contact-independent (quorum sensing, type II secretion) antagonism pathways to interrogate the mechanism of action. Our results indicate that well-known mechanisms of interbacterial competition are not responsible for the antagonism of P. aeruginosa toward M. abscessus, suggesting a novel antibacterial strategy. IMPORTANCE The biofilm lifestyle is favored by many organisms, and understanding interbacterial interactions that occur between coisolated bacterial species can provide new information regarding bacterial defense mechanisms and antibacterial targets. This may also provide insights into possible interbacterial interactions impacting host immunity during coinfection. Here, we investigate an antagonistic interaction favoring P. aeruginosa over M. abscessus exclusively in dual-species biofilms and not in liquid coculture.

PMID:36394312 | DOI:10.1128/spectrum.02471-22

Int Med Case Rep J. 2022 Nov 9;15:647-656. doi: 10.2147/IMCRJ.S381078. eCollection 2022.

ABSTRACT

This article discusses common ocular manifestations of cystic fibrosis (CF) and cystic fibrosis transmembrane conductance regulator-related disorders (CFTR-RD). A structured approach for assessing and treating patients with CF/CFTR-RD seeking corneal refractive surgery is proposed, as well as a novel surgical risk scoring system. We also report two patients with various manifestations of CFTR dysfunction who presented for refractive surgery and the outcomes of the procedures. Surgeons seeking to perform refractive surgery on patients with CF/CFTR-RD should be aware of mild to severe clinical manifestations of CFTR dysfunction. Specific systemic and ocular manifestations of CF include chronic obstructive pulmonary disease (COPD), bronchiectasis, recurrent pulmonary infections, CF-related diabetes and liver disease, pancreatic insufficiency, conjunctival xerosis, night blindness, meibomian gland dysfunction (MGD), and blepharitis. Corneal manifestations include dry eye disease (DED), punctate keratitis (PK), filamentary keratitis (FK), xerophthalmia, and decreased endothelial cell density and central corneal thickness. Utilization of the appropriate review of systems (ROS) and screening tests will assist in determining if the patient is a suitable candidate for refractive surgery, as CF/CFTR-RD can impact the health of the cornea. Collaboration with other medical professionals who care for these patients is encouraged to ensure that their CF/CFTR-RD symptoms are best controlled via systemic and other treatment options. This will assist in reducing the severity of their ocular manifestations before and after surgery.

PMID:36388243 | PMC:PMC9656410 | DOI:10.2147/IMCRJ.S381078

Oncoimmunology. 2022 Nov 14;11(1):2146855. doi: 10.1080/2162402X.2022.2146855. eCollection 2022.

ABSTRACT

Writing in Science, Al Habsi et al. show that spermidine boosts the efficacy of monoclonal antibodies targeting PD-L1 in aged tumor-bearing mice by enhancing fatty acid oxidation in CD8 T cells. These results open new therapeutic avenues to improve the effectiveness of anticancer immunotherapies in aged patients.

PMID:36387057 | PMC:PMC9665084 | DOI:10.1080/2162402X.2022.2146855