Examining the Association between Immunosuppressants and Wound Healing: A Narrative Review.

OBJECTIVE: To review how different classes of immunosuppressants affect wound healing. DATA SOURCES: A literature search was conducted in PubMed, Google Scholar, and the University of Calgary Health Sciences Library. STUDY SELECTION: The researchers initially screened article titles using key words such as "immunosuppressive medication," "wound healing," and "immunosuppression." Articles in which the title and/or abstract contained these key words, that addressed wound healing related to immunosuppressant medications, and were published after 2000 were included in the review. When human data were not available for an immunosuppressant (class), animal studies were included. DATA EXTRACTION: The 61 included articles underwent full text review and summarization. DATA SYNTHESIS: All included studies were summarized descriptively including immunosuppressive mechanism of action, study participants or subjects, and evidence of effects on wound healing. CONCLUSIONS: Corticosteroids and mechanistic target of rapamycin inhibitors most consistently demonstrate detrimental effects on wound healing. For other classes of immunosuppressants, evidence is limited with varying effects on wound healing described. Larger, high-quality studies are required to better understand the effects of immunosuppressants, including those with new mechanisms of action, to identify those with the most impact on wound healing.

Porcine-derived pancreatic enzyme replacement therapy may be linked to chronic hepatitis E virus infection in cystic fibrosis lung transplant recipients.

OBJECTIVES: In high-income countries hepatitis E virus (HEV) is an uncommonly diagnosed porcine-derived zoonoses. After identifying disproportionate chronic HEV infections in persons with cystic fibrosis (pwCF) postlung transplant, we sought to understand its epidemiology and potential drivers. DESIGN: All pwCF post-transplant attending our regional CF centre were screened for HEV. HEV prevalence was compared against non-transplanted pwCF and with all persons screened for suspected HEV infection from 2016 to 2022 in Alberta, Canada. Those with chronic HEV infection underwent genomic sequencing and phylogenetic analysis. Owing to their swine derivation, independently sourced pancreatic enzyme replacement therapy (PERT) capsules were screened for HEV. RESULTS: HEV seropositivity was similar between transplanted and non-transplanted pwCF (6/29 (21%) vs 16/83 (19%); p=0.89). Relative to all other Albertans investigated for HEV as a cause of hepatitis (n=115/1079, 10.7%), pwCF had a twofold higher seropositivity relative risk and this was four times higher than the Canadian average. Only three chronic HEV infection cases were identified in all of Alberta, all in CF lung transplant recipients (n=3/29, 10.3%). Phylogenetics confirmed cases were unrelated porcine-derived HEV genotype 3a. Ninety-one per cent of pwCF were taking PERT (median 8760 capsules/person/year). HEV RNA was detected by RT-qPCR in 44% (47/107) of PERT capsules, and sequences clustered with chronic HEV cases. CONCLUSION: PwCF had disproportionate rates of HEV seropositivity, regardless of transplant status. Chronic HEV infection was evident only in CF transplant recipients. HEV may represent a significant risk for pwCF, particularly post-transplant. Studies to assess HEV incidence and prevalence in pwCF, and potential role of PERT are required.

Association between Serum Estradiol and Cardiovascular Health among Transgender Adults Using Gender-Affirming Estrogen Therapy.

INTRODUCTION: Gender-affirming estrogen therapy (GAET) is commonly used for feminization in transgender and non-binary (TNB) individuals, yet the optimal rate of change (ROC) in estradiol levels for cardiovascular health is unclear. We examined the association between serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET. METHODS: Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE and Web of Science were systematically searched (inception-April 2023) for original articles reporting serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET. Data extraction was completed in duplicate following PRISMA guidelines. Stratified random effects meta-analyses using serum estradiol ROC (serum estradiolbaseline-serum estradiolfollow-up/study duration) was used to assess longitudinal studies (Low:0

Correction: Clinical epidemiology and outcomes of community acquired infection and sepsis among hospitalized patients in a resource limited setting in Northeast Thailand: A prospective observational study (Ubon-sepsis).

[This corrects the article DOI: 10.1371/journal.pone.0204509.].

Multicentre, randomised, double-blind, placebo-controlled, proof of concept study of LSALT peptide as prevention of acute respiratory distress syndrome and acute kidney injury in patients infected with SARS-CoV-2 (COVID-19).

OBJECTIVE: Dipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19. DESIGN: Phase 2a randomised, placebo-controlled, double-blinded, trial. SETTING: Hospitals in Canada, Turkey and the USA. PARTICIPANTS: A total of 61 subjects with moderate-to-severe COVID-19. INTERVENTIONS: Randomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers. RESULTS: At 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O2 ≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups. CONCLUSION: In a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19. TRIAL REGISTRATION NUMBER: NCT04402957.

Creation of a CF-specific antibiotic spectrum index (ASI) as an antimicrobial stewardship initiative.

Antibiotics are frequently utilized for cystic fibrosis (CF)-related pulmonary exacerbation treatment. The antibiotic spectrum index (ASI) is an antimicrobial stewardship tool developed to compare the relative breadth of individual antibiotics. This study aimed to create two expanded CF-specific ASI scoring indices for use in antimicrobial stewardship research and clinical care. The first scoring index expanded the original ASI to include bacterial microorganisms common to CF airway infections (CF-ASI). The second scoring system only included scores for bacterial microorganisms classically identified in CF airway infections (CF-sASI). Sixty-two antibiotics were evaluated and included in the updated ASIs. When multiple antibiotics are prescribed, we proposed using an additive ASI approach whereby the sum of the individual prescribed antibiotic scores represents the total ASI score. The application of CF-focused ASIs into CF research and stewardship programs can help to optimize antibiotic benefits, minimize harms and allow for increased sustainability of antibiotic use in CF.

Health trends in Canada 1990-2019: An analysis for the Global Burden of Disease Study.

OBJECTIVE: Monitoring trends in key population health indicators is important for informing health policies. The aim of this study was to examine population health trends in Canada over the past 30 years in relation to other countries. METHODS: We used data on disability-adjusted life years (DALYs), years of life lost (YLL), years lived with disability, life expectancy (LE), and child mortality for Canada and other countries between 1990 and 2019 provided by the Global Burden of Disease Study. RESULTS: Life expectancy, age-standardized YLL, and age-standardized DALYs all improved in Canada between 1990 and 2019, although the rate of improvement has leveled off since 2011. The top five causes of all-age DALYs in Canada in 2019 were neoplasms, cardiovascular diseases, musculoskeletal disorders, neurological disorders, and mental disorders. The greatest increases in all-age DALYs since 1990 were observed for substance use, diabetes and chronic kidney disease, and sense organ disorders. Age-standardized DALYs declined for most conditions, except for substance use, diabetes and chronic kidney disease, and musculoskeletal disorders, which increased by 94.6%, 14.6%, and 7.3% respectively since 1990. Canada's world ranking for age-standardized DALYs declined from 9th place in 1990 to 24th in 2019. CONCLUSION: Canadians are healthier today than in 1990, but progress has slowed in Canada in recent years in comparison with other high-income countries. The growing burden of substance abuse, diabetes/chronic kidney disease, and musculoskeletal diseases will require continued action to improve population health.

RéSUMé: OBJECTIF: La surveillance des tendances des indicateurs clés de la santé de la population est importante pour éclairer les politiques de santé. Dans cette étude, nous avons examiné les tendances de la santé de la population au Canada au cours des 30 dernières années par rapport à d'autres pays. MéTHODES: Nous avons utilisé des données sur les années de vie ajustées en fonction de l'incapacité (DALY), les années de vie perdues (YLL), les années vécues avec un handicap, l'espérance de vie (LE) et la mortalité infantile pour le Canada et d'autres pays entre 1990 et 2019, fournies par l'Étude mondiale sur le fardeau de la maladie. RéSULTATS: L'espérance de vie, les YLL ajustées selon l'âge et les DALY ajustées selon l'âge ont tous connu une amélioration au Canada entre 1990 et 2019, bien que le taux d'amélioration se soit stabilisé depuis 2011. Les cinq principales causes des DALY pour tous les âges au Canada en 2019 étaient les néoplasmes, les maladies cardiovasculaires, les affections musculosquelettiques, les affections neurologiques et les troubles mentaux. Les plus fortes augmentations des DALY pour tous les âges depuis 1990 ont été observées pour l'usage de substances, le diabète et les maladies rénales chroniques, ainsi que les troubles des organes sensoriels. Les DALY ajustées selon l'âge ont diminué pour la plupart des conditions, à l'exception de l'usage de substances, du diabète et des maladies rénales chroniques, ainsi que des troubles musculosquelettiques, qui ont augmenté de 94,6 %, 14,6 % et 7,3 % respectivement depuis 1990. Le classement mondial du Canada pour les DALY ajustées selon l'âge est diminué de la 9ième place en 1990 à la 24ième place en 2019. CONCLUSION: Les Canadiens sont en meilleure santé aujourd'hui qu'en 1990, mais les progrès se sont ralentis ces dernières années par rapport à d'autres pays à revenu élevé. La croissance du fardeau lié à l'abus de substances, au diabète/maladies rénales chroniques et aux affections musculosquelettiques exigera des actions continues pour améliorer la santé de la population.

The Use of Silver Oxynitrate Wound Dressings in the Treatment of Chronic Wounds: A Feasibility Pilot Study.

OBJECTIVE: To evaluate the feasibility and effectiveness of a silver oxynitrate (Ag 7 NO 11 ) dressing on wound healing in patients with stalled chronic wounds. METHODS: A prospective pilot study was conducted to determine the feasibility and effect of using silver oxynitrate dressings within an outpatient setting in Alberta, Canada. A total of 23 patients (12 women and 11 men; mean age, 66.1 ± 13.8 years) with a chronic wound that failed to heal with conventional treatment were included in the study. Wound assessments including the Bates-Jensen Wound Assessment Tool, wound-related pain, wound size, and patient quality of life (QoL) were conducted at baseline, after dressing application for 1 and 2 weeks, and during 4- and 12-week follow-ups. RESULTS: Dressing application at 1 and 2 weeks improved patients' wound healing progression as measured through significantly decreased Bates-Jensen Wound Assessment Tool scores with a more than 10% decrease at 4- and 12-week follow-up ( P < .001). Pain ( P = .004), and QoL psyche subscore ( P = .008) significantly improved at 4-week follow-ups, although wound area, perimeter, and QoL body and everyday subscores were not significantly affected. Wound size was not significantly affected. CONCLUSIONS: The silver oxynitrate dressing may improve healing progression in patients with chronic wounds, enhance patient experience by reducing wound-related pain, and improve patients' mental well-being. Further studies are warranted to elucidate the effect of silver oxynitrate dressings on wound area, perimeter, and volume measurements.

Evaluating Sinus Microbiology by Transplant Status in Persons With Cystic Fibrosis: A Matched Cohort Study.

Objective: Sinus disease is prevalent in persons with cystic fibrosis (PwCF) and may be a reservoir of airway infection in postlung transplant (pTx) patients. The microbial composition of cystic fibrosis sinuses and its associations with chronic rhinosinusitis (CRS) is relatively unexplored. We aimed to examine the sinus and lower airway microbiome and their associations with CRS in PwCF and pTxPwCF. Study Design: Prospective single-centre study. Setting: A total of 31 sex and age (±2 years) matched PwCF and pTxPwCF. Methods: Demographic and clinical data along with sinus swabs and sputum were collected. CRS was assessed using Sinonasal Outcome Test-22 (SNOT-22) (patient reported outcome) and Lund-McKay (computed tomography sinus) scores. Samples underwent MiSeq Illumina sequencing of the universal 16S ribosomal RNA gene. Results: A total of 31 PwCF (15 pTxPwCF) were included. Aggregate airways microbiome composition was dominated by Pseudomonas (46%), Haemophilus (14%), Staphylococcus (11%), Streptococcus (10%), and Fusobacterium (6%). α-diversity was significantly lower in post-Tx samples across both sputum and sinus samples (P = .005). ß-diversity was significantly different between sputum (P = .004), but not sinus (P = .75) samples by transplant status. While there was a trend in higher ß-diversity associated with lower SNOT-22 score at time of first visit, this did not reach significance (P = .05). Conclusion: Sinus and airway microbiomes differed in PwCF and pTxPwCF, but the prevalent organisms remained consistent. Elucidating the relationship of the microbiome with clinical status to better understand when to intervene accordingly is needed to optimize sinus disease management in PwCF.

Wound Bed Preparation 2024: Delphi Consensus on Foot Ulcer Management in Resource-Limited Settings.

GENERAL PURPOSE: To review a practical and scientifically sound application of the wound bed preparation model for communities without ideal resources. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Summarize issues related to wound assessment.2. Identify a class of drugs for the treatment of type II diabetes mellitus that has been shown to improve glycemia, nephroprotection, and cardiovascular outcomes.3. Synthesize strategies for wound management, including treatment in resource-limited settings.4. Specify the target time for edge advancement in chronic, healable wounds.

Chronic wound management in low-resource settings deserves special attention. Rural or underresourced settings (ie, those with limited basic needs/healthcare supplies and inconsistent availability of interprofessional team members) may not have the capacity to apply or duplicate best practices from urban or abundantly-resourced settings. The authors linked world expertise to develop a practical and scientifically sound application of the wound bed preparation model for communities without ideal resources. A group of 41 wound experts from 15 countries reached a consensus on wound bed preparation in resource-limited settings. Each statement of 10 key concepts (32 substatements) reached more than 88% consensus. The consensus statements and rationales can guide clinical practice and research for practitioners in low-resource settings. These concepts should prompt ongoing innovation to improve patient outcomes and healthcare system efficiency for all persons with foot ulcers, especially persons with diabetes.

National burden of rheumatoid arthritis in Canada, 1990-2019: findings from the Global Burden of Disease Study 2019 - a GBD collaborator-led study.

OBJECTIVE: The objectives of this study were: (1) to describe burden of rheumatoid arthritis (RA) and trends from 1990 to 2019 using the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) data, (2) to describe age and sex differences in RA and (3) to compare Canada's RA burden to that of other countries. METHODS: Disease burden indicators included prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs) and disability-adjusted life-years (DALYs). GBD estimated fatal and non-fatal outcomes using published literature, survey data and health insurance claims. Data were analysed by Bayesian meta-regression, cause of death ensemble model and other statistical methods. DALYs for Canada were compared with DALYs of countries with similarly high Socio-Demographic Index values. RESULTS: In Canada, the RA prevalence rate increased by 27% between 1990 and 2019, mortality rate decreased by 27%, YLL rate decreased by 30%, YLD increased by 27% and DALY rate increased by 13%, all age standardised. The decline in RA mortality and YLL rates was especially pronounced after 2002. The disease burden was higher in females for all indicators, and DALY rates were higher among older age groups, peaking at age 75-79 years. Prevalence and DALYs were higher in Canada compared with global rates. CONCLUSION: Trends in RA burden indicators over time and differences by age and sex have important implications for Canadian policy-makers, researchers and care providers. Early identification and management of RA in women may help reduce the overall burden of RA in Canada.

Evaluating the impact of a SIMPlified LaYered consent process on recruitment of potential participants to the Staphylococcus aureus Network Adaptive Platform trial: study protocol for a multicentre pragmatic nested randomised clinical trial (SIMPLY-SNAP trial).

INTRODUCTION: Informed consent forms (ICFs) for randomised clinical trials (RCTs) can be onerous and lengthy. The process has the potential to overwhelm patients with information, leading them to miss elements of the study that are critical for an informed decision. Specifically, overly long and complicated ICFs have the potential to increase barriers to trial participation for patients with mild cognitive impairment, those who do not speak English as a first language or among those with lower medical literacy. In turn, this can influence trial recruitment, completion and external validity. METHODS AND ANALYSIS: SIMPLY-SNAP is a pragmatic, multicentre, open-label, two-arm parallel-group superiority RCT, nested within a larger trial, the Staphylococcus aureus Network Adaptive Platform (SNAP) trial. We will randomise potentially eligible participants of the SNAP trial 1:1 to a full-length ICF or a SIMPlified LaYered (SIMPLY) consent process where basic information is summarised with embedded hyperlinks to supplemental information and videos. The primary outcome is recruitment into the SNAP trial. Secondary outcomes include patient understanding of the clinical trial, patient and research staff satisfaction with the consent process, and time taken for consent. As an exploratory outcome, we will also compare measures of diversity (eg, gender, ethnicity), according to the consent process randomised to. The planned sample size will be 346 participants. ETHICS AND DISSEMINATION: The study has been approved by the ethics review board (Sunnybrook Health Sciences Research Ethics Board) at sites in Ontario. We will disseminate study results via the SNAP trial group and other collaborating clinical trial networks. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT06168474; www. CLINICALTRIALS: gov).

Randomized trial of the safety and efficacy of anti-SARS-CoV-2 mAb in the treatment of patients with nosocomial COVID-19 (CATCO-NOS).

Background: Patients with nosocomial acquisition of COVID-19 have poor outcomes but have not been included in therapeutic trials to date. Methods: A pragmatic open-label randomized controlled trial of anti-SARS-CoV-2 monoclonal antibodies (mAb) was performed in hospitalized patients with nosocomial COVID-19 infection in acute care hospitals spanning a provincial health care network. Participants within 5 days of first positive test or symptom onset were randomized to standard of care (SOC) plus a single dose intravenous mAb treatment (bamlanivimab or casirivimab/imdevimab) or SOC alone on a 2:1 basis. The primary study endpoint was the need for invasive mechanical ventilation (IMV) or inpatient mortality by day 60 after randomization. Results: Forty-six participants were enrolled from 13 hospitals between February 14 and October 8, 2021: 31 in the mAb and 15 in the SOC arm. IMV or inpatient mortality up to day 60 occurred in 4 (12.9%) participants in the mAb versus 3 in the SOC arm (20.0%), difference of -7.1% (95% CI -22.5 to 13.4, p = 0.67). The study was terminated early due to lack of equipoise as effectiveness of anti-viral therapies and mAb was published in similar high-risk patient populations. Conclusions: The trial was underpowered to detect meaningful differences given its early termination. The study does highlight the feasibility of undertaking trials in this patient population using a pragmatic approach allowing for trial participation and treatment access across a large health care network and may serve as a template for future designs.

Historique: Les patients qui contractent une COVID-19 nosocomiale ont de mauvais résultats cliniques, mais n'ont pas fait partie des études thérapeutiques jusqu'à présent. Méthodologie: Les chercheurs ont mené une étude randomisée et contrôlée ouverte et pragmatique des anticorps monoclonaux (AcM) anti-SRAS-CoV-2 auprès de patients hospitalisés qui ont contracté une COVID-19 nosocomiale dans les hôpitaux de soins aigus d'un réseau de santé provincial. Dans les cinq jours suivant un premier test positif ou l'apparition des symptômes, les participants ont été divisés de manière randomisée entre la norme des soins (NdS) combinée à une monodose de traitement aux AcM par voie intraveineuse (bamlanivimab ou casirivimab-imdevimab) ou la NdS seule sur une base de deux pour un. Le critère d'évaluation primaire de l'étude était la ventilation mécanique invasive (VMI) ou la mortalité en milieu hospitalier le 60e jour après la randomisation. Résultats: Au total, 46 participants de 13 hôpitaux ont été inclus entre le 14 février et le 8 octobre 2021, soit 31 patients du volet des AcM et 15 du volet de la NdS. La VMI ou la mortalité en milieu hospitalier jusqu'au 60e jour a été observée chez quatre participants au volet des AcM (12,9 %) et trois participants du volet de la NdS (20,0 %), soit une différence de −7,1 % (IC à 95 %, −22,5 à 13,4, p = 0,67). L'étude a été interrompue précocement à cause de l'absence d'équilibre clinique, car des données sur l'efficacité des traitements antiviraux et des AcM ont été publiées au sujet de populations semblables de patients à haut risque. Conclusions: L'échantillon à l'étude était insuffisant pour déceler des différences significatives compte tenu de son interruption précoce. Cette recherche fait ressortir la faisabilité d'études auprès de cette population de patients au moyen d'une approche pragmatique pour y inclure des participants et accéder au traitement dans un vaste réseau de soins et pourrait servir de modèle pour concevoir d'autres études.

Necrotizing Soft-Tissue Infections: A Case-Based Review.

GENERAL PURPOSE: To review the assessment and management of necrotizing fasciitis. TARGET AUDIENCE: This continuing-education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Identify the etiologic pathogens for necrotizing fasciitis.2. Summarize assessment guidelines for patients who present with signs of necrotizing fasciitis.3. Explain recommended treatment protocols for patients who have necrotizing fasciitis.

Necrotizing fasciitis is a rapidly progressive soft-tissue infection with tissue necrosis and a high mortality rate. This case-based review provides an overview of an approach to the diagnosis and management of necrotizing fasciitis for clinicians.

Prevalence and impact of human papillomavirus (HPV) in adults with cystic fibrosis: A self-reported cross-sectional Canadian survey.

BACKGROUND: In persons with cystic fibrosis (pwCF), little is known about the prevalence or impact of HPV on quality of life and attitudes towards vaccination. METHODS: We conducted a national online survey of adult pwCF. We sought to determine the prevalence of self-reported HPV infection, disease-associated complications and effects on quality of life. Additionally, we investigated factors associated with vaccination status. RESULTS: A total of 235 adult pwCF across Canada (≥18 years, 68% female) completed the survey. Forty-eight percent of female pwCF had a history of abnormal Pap smear, with 62% self-reporting a 'no' or 'low' chance of risk of HPV-associated disease. Across participants, 12% reported at least one HPV-associated complication including anogenital warts (58%), HPV-associated malignancies (34%) and cervical dysplasia requiring colposcopy (69%). Only 19% reported discussions with their CF care provider around HPV complications. Across both sexes, pwCF experienced high psychosocial burden in the domains of 'worries and concerns', 'sexual impact' and 'self-image'. Sixty percent of adult pwCF were unvaccinated for HPV. Eighty-one percent reported never having discussed HPV vaccination with their CF care provider, with similar rates in vaccinated and unvaccinated groups. Barriers to vaccination included: lack of discussions with healthcare providers (31%), insured coverage (based on age) (19%) and perceived side effects/risk (10%). CONCLUSIONS: Across adult pwCF, we found high prevalence of HPV disease and associated HPV-psychosocial burden and low vaccination uptake. Given the limited medical discussions reported, incorporation of HPV prevention and management should be prioritized by CF care providers as part of comprehensive multimodal care.

Breath of fresh insight: unraveling the evolution of our understanding of cystic fibrosis pulmonary exacerbations.

PURPOSE OF REVIEW: Pulmonary exacerbations are critical events with significant negative impacts in persons with cystic fibrosis, but their diagnosis and management are highly variable. Highly effective modulator therapies have greatly improved health and reduced exacerbation events, but have also reshaped how they present. This review discusses the complexities of the diagnosis and management of pulmonary exacerbations as well as the emerging work and evidence in this area. RECENT FINDINGS: The shifting epidemiology and our understanding of risk factors for pulmonary exacerbations are discussed. As symptoms may be more subtle in the modulator context, novel technologies including studies of remote monitoring are presented. The continued relevance of pulmonary exacerbations, the heterogeneity in their management, as well as current and forthcoming clinical trials to optimize treatment approaches are detailed. SUMMARY: In spite of the dramatic reductions in pulmonary exacerbations, airway infections persist, a proportion of persons with cystic fibrosis either on or off modulator therapies continue to experience exacerbation events, and long-term data is lacking. Innovative approaches and studies will be crucial to enable standardized and generalizable strategies to improve outcomes in persons with cystic fibrosis.

Stenotrophomonas maltophilia natural history and evolution in the airways of adults with cystic fibrosis.

Introduction: Stenotrophomonas maltophilia is an opportunistic pathogen infecting persons with cystic fibrosis (pwCF) and portends a worse prognosis. Studies of S. maltophilia infection dynamics have been limited by cohort size and follow-up. We investigated the natural history, transmission potential, and evolution of S. maltophilia in a large Canadian cohort of 321 pwCF over a 37-year period. Methods: One-hundred sixty-two isolates from 74 pwCF (23%) were typed by pulsed-field gel electrophoresis, and shared pulsotypes underwent whole-genome sequencing. Results: S. maltophilia was recovered at least once in 82 pwCF (25.5%). Sixty-four pwCF were infected by unique pulsotypes, but shared pulsotypes were observed between 10 pwCF. In chronic carriage, longer time periods between positive sputum cultures increased the likelihood that subsequent isolates were unrelated. Isolates from individual pwCF were largely clonal, with differences in gene content being the primary source of genetic diversity objectified by gene content differences. Disproportionate progression of CF lung disease was not observed amongst those infected with multiple strains over time (versus a single) or amongst those with shared clones (versus strains only infecting one patient). We did not observe evidence of patient-to-patient transmission despite relatedness between isolates. Twenty-four genes with ≥ 2 mutations accumulated over time were identified across 42 sequenced isolates from all 11 pwCF with ≥ 2 sequenced isolates, suggesting a potential role for these genes in adaptation of S. maltophilia to the CF lung. Discussion: Genomic analyses suggested common, indirect sources as the origins of S. maltophilia infections in the clinic population. The information derived from a genomics-based understanding of the natural history of S. maltophilia infection within CF provides unique insight into its potential for in-host evolution.