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INTRODUCTION: Chronic rhinosinusitis is common among individuals with cystic fibrosis (CF) and has an impact on quality of life. Sinus surgery is a treatment option, but minimal literature exists regarding prevalence and indications. METHODS: Using the linked CF Foundation Patient Registry (CFFPR) - Pediatric Health Information Systems (PHIS) database, we investigated variability in receipt of surgery, predictors of surgery, and time to first surgery. We included individuals less than 18 receiving care between 2006 and 2015 at a CF Foundation care program that is also a PHIS-participating-hospital. We used logistic regression to examine predictors of receipt of surgery and a Kaplan-Meier curve to examine time to first surgery among those born 2005-2007. RESULTS: There were 11,545 children and adolescents and 2156 (18.7%) received at least one surgery. Variation in number of surgeries was observed across hospitals (median: 63 [IQR, 33-110]). There was an inconsistent pattern between receipt of surgery and markers of disease severity; those receiving surgery having increased odds of treatment use and pulmonary exacerbations and decreased odds of lower lung function and body mass index. Among the cohort of young children, 159 (14%) had at least one surgery with a median age at first surgery of 5.6 (IQR, 3.9-7.0). CONCLUSIONS: The use of sinus surgery is frequent, but variable, among children and adolescents. Clinical factors are associated with receipt of surgery, but further understanding is needed on other factors that impact variability in use. Our study indicates the need for additional evaluation of the management of CF-related CRS and indications for surgery.
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Fibrosis Quística , Sinusitis , Adolescente , Niño , Preescolar , Enfermedad Crónica , Fibrosis Quística/complicaciones , Fibrosis Quística/epidemiología , Fibrosis Quística/cirugía , Humanos , Prevalencia , Calidad de Vida , Sinusitis/complicaciones , Sinusitis/epidemiología , Sinusitis/cirugíaRESUMEN
BACKGROUND: Cardiac surgery-associated acute kidney injury (AKI) is an adverse outcome that increases morbidity and mortality in patients undergoing cardiac surgical procedures. To date, the use of serum creatinine levels as an early indicator of AKI has limitations because of its slow rise and poor predictive accuracy for renal injury. This delay in diagnosis may lead to prolonged initiation in treatment and increased risk for adverse outcomes. OBJECTIVE: This pilot study explores serum and urine matrix metalloproteinases (MMPs)-2 and MMP-9 and their association, and potentially earlier detection of AKI in patients following cardiopulmonary bypass (CPB)-supported cardiac surgery. We hypothesize that increased activity of serum and urine levels MMP-2 and/ or MMP-9 are associated with AKI. Furthermore, MMP-2 and/ or MMP-9 may provide earlier identification of AKI as compared with serum levels of creatinine. METHODS: During the study period, there were 150 CPB-supported surgeries, 21 of which developed AKI according to the Kidney Disease Improving Global Outcomes criteria. We then selected a sample of 21 matched cases from those patients who went through the surgery without developing AKI. Primary outcomes were the measurement via gel zymography of the serum and urine activity of MMP-2 and MMP-9 drawn at the following intervals: pre-CPB; 10-minute post-CPB; and 4-hour post-CPB time points. Secondary variables were the measurement of serum creatinine, intensive care unit (ICU) fluid balance, and length of ICU stay. RESULTS: At the 10-minute and 4-hour post-CPB time points, the serum MMP-2 activity of AKI patients were significantly higher as compared with non-AKI patients (P < .001 and P = .004), respectively. Similarly, at the 10-minute and 4-hour post-CPB time points, the serum MMP-9 activity of AKI patients was significantly higher as compared with non-AKI patients (P = .001 and P = .014), respectively. The activity of urine MMP-2 and MMP-9 of AKI patients was significantly higher as compared with non-AKI patients at all 3 time points (P = .004, P < .001, P < .001), respectively. CONCLUSION: Although the pilot study may have limitations, it has demonstrated that the serum and urine levels of activity of MMP-2 and MMP-9 are associated with the clinical endpoint of AKI and appear to have earlier rising levels as compared with those of serum creatinine. Furthermore, in depth, exploration is underway with a larger sample size to attempt validation of the analytical performance and reproducibility of the assay for MMP-2 and MMP-9 to aid in earlier diagnosis of AKI following CPB-supported cardiac surgery.
CONTEXTE: L'insuffisance rénale aiguë (IRA) associée à la chirurgie cardiaque est un effet indésirable qui augmente la morbidité et la mortalité des patients qui subissent ce type d'intervention. La mesure de la créatinine sérique comme indicateur précoce de l'IRA continue à ce jour de présenter des limites en raison de sa lente augmentation et de l'imprécision de son pouvoir prédictif. Ce délai dans le diagnostic peut retarder l'initiation du traitement et accroître le risque d'effets indésirables. OBJECTIFS: Cette étude pilote explore les métalloprotéinases matricielles (MPM) -2 et -9 sériques et urinaires, leur association avec l'IRA et leur potentiel pour la détection plus précoce de la maladie chez les patients qui subissent une chirurgie cardiaque assistée par circulation extracorporelle. Nous émettons l'hypothèse qu'une hausse de l'activité des MMP-2 et/ou -9 et de leurs taux sériques et urinaires serait associée à l'IRA. Les MMP-2 et/ou -9 pourraient en outre permettre d'identifier la maladie plus précocement que le taux de créatinine sérique. MÉTHODOLOGIE: Au cours de la période de l'étude, 150 chirurgies cardiaques assistées par circulation extracorporelle ont été effectuées et 21 ont été associées à une IRA telle que définie par les critères du KDIGO (Kidney Disease Improving Global Outcomes). Nous avons sélectionné 21 cas appariés parmi les patients ayant subi l'intervention sans développer d'IRA. Le principal critère d'évaluation était une mesure de l'activité des MMP-2 et -9 obtenue par une zymographie sur gel d'échantillons de sérum et d'urine prélevés aux intervalles suivants: pré-circulation extracorporelle, 10 minutes après la circulation extracorporelle et 4 heures après la circulation extracorporelle. Les variables secondaires étaient la mesure de la créatinine sérique, la mesure de la balance liquidienne durant le séjour à l'unité de soins intensifs (USI) et de la durée du séjour à l'USI. RÉSULTATS: L'activité des MMP-2 sériques des patients atteints d'IRA était significativement plus élevée que celle des patients non atteints d'IRA 10 minutes et 4 heures post-circulation extracorporelle (p < 0,001 et p = 0,004 respectivement). Aux mêmes repères temporels, l'activité des MMP-9 sériques était elle aussi significativement plus élevée chez les patients atteints d'IRA (p = 0,001 [IRA]; p = 0,014 (non IRA). L'activité des MMP-2 et -9 urinaires, elle était elle aussi significativement plus élevée pour les patients atteints d'IRA, et ce, pour les trois points temporels (p = 0,004 [IRA); p < 0,001 [non IRA]). CONCLUSION: Bien que cette étude pilote comporte des limites, elle a tout de même démontré que l'activité des MMP-2 et -9 sériques et urinaires est associée aux paramètres cliniques de l'IRA, et que leurs taux augmentent plus rapidement que les taux de créatinine sérique. Des recherches plus approfondies sur un plus grand échantillon de patients sont en cours afin de valider la performance analytique et la reproductibilité du dosage des MMP-2 et -9 pour diagnostiquer plus rapidement l'IRA après une chirurgie cardiaque assistée par circulation extracorporelle.
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The care for individuals with cystic fibrosis (CF) with at least one F508del mutation will greatly change as a result of the unparalleled clinical benefits observed with the new triple-combination CFTR (CF transmembrane regulator)-modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI). Incorporating ETI into the standard of care creates new motivation and opportunity to consider reductions in overall treatment burden and evaluate whether other chronic medications can now be safely discontinued without loss of clinical benefit. SIMPLIFY is a master protocol poised to test the impact of discontinuing versus continuing two commonly used chronic therapies in people with CF who are at least 12 years of age or older and stable on ETI therapy. The protocol is composed of two concurrent randomized controlled trials designed to evaluate the independent short-term effects of discontinuing hypertonic saline or dornase alfa, enabling individuals on both therapies to participate in one or both trials. The primary objective for each trial is to determine whether discontinuing treatment is noninferior to continuing treatment after establishment of ETI, as measured by the 6-week absolute change in the percent-predicted forced expiratory volume in 1 second. Developing this study required a balance between ideal study-design principles and feasibility. SIMPLIFY will be the largest multicenter, randomized, controlled medication-withdrawal study in CF. This study is uniquely positioned to provide timely evidence on whether the daily treatment burden can be reduced among individuals on CFTR-modulator therapy. Clinical trial registered with www.clinicaltrials.gov (NCT04378153).
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Fibrosis Quística , Quinolonas , Aminofenoles/uso terapéutico , Benzodioxoles/uso terapéutico , Fibrosis Quística/tratamiento farmacológico , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , HumanosRESUMEN
Individuals living with cystic fibrosis (CF), and their families, have experienced significant improvements in treatment and related research that have enhanced outcomes and survival. Despite such advancement, the burden of living with CF still exists. Many psychosocial stressors and risk factors are associated with the impact of CF. The identification and treatment of such risk factors are discussed throughout this review, with an emphasis on strategies to address psychosocial risk and the importance of promoting resiliency in those touched by CF.