OBJECTIVE. Left atrial thrombi are an important cause for embolism-related morbidity and mortality. Transesophageal echocardiography (TEE), the clinical reference, is semiinvasive; thus, we aimed to assess the value of contrast-enhanced cardiovascular MRI for the detection of thrombus in the left atrial appendage.CONCLUSION. The image quality was good for both 2D perfusion (grade 4 ± 1) and 3D turbo fast low-angle shot (FLASH) (grade 4 ± 1, n.s.). Compared with TEE, 2D perfusion, 3D turboFLASH, and the combination of both techniques yielded sensitivities of 47/35/44%, specificities of 50/67/67%, positive predictive values of 73/75/80%, and negative predictive values of 25/27/29%, respectively. The size of the thrombus was overestimated by 2D perfusion (66%) and by 3D turboFLASH (25%) and agreement for location and shape of thrombus was 50% and 75% for 2D perfusion and 75% and 50% for 3D turboFLASH, respectively. The TEE thrombus size was significantly larger in patients with true-positive diagnoses by 2D ...

Background: Sleep-disordered breathing (SDB) and disturbed sleep are common, often underrecognized, comorbidities in people with cystic fibrosis (pwCF). Objectives: We studied the effect of CFTR triple combination therapy elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on sleep in pwCF. Method: This was a prospective, observational sleep study in clinically stable adult pwCF. All participants underwent overnight polysomnography (PSG), before (T0) and after (T1) initiation of CFTR modulator therapy with ELX/TEZ/IVA. In addition, pulmonary function tests, calculation of BMI, and sweat chloride testing were performed. Results: Twenty-nine pwCF (mean age 32 ± 8 years; 15 female) participated in the study. Mean time between T0 and T1 was 194 ± 21 days. Total sleep time (TST) was 298 ± 40 min, with decreased sleep efficiency (SE) (76 ± 109) and increased sleep latency (SL) (73 ± 38 min). Sleep stages for NREM (N1–3) and REM sleep were within the normal range. Nocturnal respiratory events mainly occur during REM sleep (T0: AHI REM 8.3 ± 9.0/h; ODI REM 9.4 ± 10.6/h), whereas the overall AHI was normal (3.6 ± 3.7/h). After initiation of ELX/TEZ/IVA, we saw significant improvements in ppFEV1 (p < 0.001) and BMI (p < 0.001) and a reduction in sweat chloride levels (p < 0.001). In parallel, there was a reduction in AHI (p = 0.003), ODI (p = 0.001), and nocturnal respiratory rate (p < 0.001), both in total, REM and NREM sleep. Neither TST, SL, SE, nor sleep architecture was influenced (all p > 0.05). Conclusions: Initiation of ELX/TEZ/IVA resulted in significant improvements in SDB in adult pwCF.

Cystic fibrosis (CF) is associated with dysregulated immune responses, exaggerated inflammation and chronic infection. CF transmembrane conductance regulator (CFTR) modulator therapies directly target the underlying protein defects and resulted in significant clinical benefits for people with CF (pwCF). This study analysed the effects of triple CFTR modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI) on CF-associated inflammation, especially systemic chemokines. A bead-based immunoassay was used to quantify proinflammatory chemokines (IL-8, IP-10, Eotaxin, TARC, RANTES, MIP-1α, MIP-1β, MIP-3α, MIG, ENA-78, GROα, I-TAC) in plasma samples from pwCF collected before, at three, and at six months after starting ETI therapy. Fifty-one pwCF (47 % female; mean age 32 ± 10.4 years) were included. At baseline, 67 % were already receiving CFTR modulator therapy with tezacaftor/ivacaftor or lumacaftor/ivacaftor. After initiation of ETI therapy there was a significant improvement in percent predicted forced expiratory volume in 1 s (+12.7 points, p < 0.001) and a significant decrease in sweat chloride levels (-53.6 %, p < 0.001). After 6 months' treatment with ETI therapy there were significant decreases in plasma levels of MIP-3α (-68.2 %, p = 0.018), GROα (-17.7 %, p = 0.013), ENA-78 (-16.3 %, p = 0.034) and I-TAC (-3.4 %, p = 0.032). IL-8 exhibited a reduction that did not reach statistical significance (-17.8 %, p = 0.057); levels of other assessed cytokines did not change significantly from baseline. ETI appears to affect a distinct group of chemokines that are predominately associated with neutrophilic inflammation, demonstrating the anti-inflammatory properties of ETI therapy.

Background: Obstructive sleep apnea (OSA), nocturnal hypoxemia and excessive daytime sleepiness (EDS) are common comorbidities in people with cystic fibrosis (pwCF). Most of the data showing this originates from children and adolescents. The aim of this study was to collect data on sleep parameters, EDS and pulmonary function from a large cohort of adult pwCF. Methods: Full overnight polysomnography (PSG) was performed. EDS was determined using the Epworth Sleepiness Scale (ESS). Demographic and clinical data (body mass index [BMI], pulmonary function, capillary blood gases) were collected. Results: A total of 52 adult pwCF were included (mean age 30.7 ± 8.0 years, mean percent predicted forced expiratory volume in 1 s [ppFEV₁] of 52.1 ± 14.8). Overall AHI was in the normal range (4.5 ± 4.0/h); 21/52 pwCF (40%) had an apnea-hypopnea index > 5/h. Nocturnal hypoxemia was found in 25% of participants and this was associated with ppFEV₁ (p = 0.014), awake oxygen saturation (SpO₂; p = 0.021) and awake partial pressure of oxygen (pO₂; p = 0.003); there were no significant differences in age, lung function and BMI were found for pwCF with versus without OSA (all p > 0.05). Eight pwCF (15%) had an ESS score > 10 (indicating EDS). OSA was best predicted by awake pO₂ (area under the curve [AUC] 0.66, p = 0.048), while nocturnal hypoxemia was best predicted by ppFEV₁ (AUC 0.74, p = 0.009), awake pO₂ (AUC 0.76, p = 0.006) and awake SpO₂ (AUC 0.71; p = 0.025). Conclusion: OSA, nocturnal hypoxemia and EDS were common in adult pwCF, but no strong predictors were identified. Therefore, we suggest regular PSG and ESS scoring in adult pwCF, regardless of disease severity.

Background. Regular physical activity plays an important role in the treatment of patients with cystic fibrosis (CF). This study is aimed at investigating the effects of a 12-month partially supervised exercise program on attributes of health-related and motor performance fitness, lung function (ppFEV1), BMI, and habitual physical activity (HPA, steps/day) in adults with CF. Methods. Attributes of health-related and motor performance fitness were examined at the beginning (T0), after 6 (T1), and 12 months (T2) on the basis of five test items: forward bend (FB), bent knee hip extension (HE), plank leg raise (PLR), standing long jump (SLJ), and standing on one leg (OLS). Additionally, we recorded HPA by accelerometry, peak exercise performance (W-peak) by an incremental cycle test, ppFEV1, and BMI. During the first six months, there was close supervision by an experienced sport therapist. Results. 26 CF patients (8 female, mean age 26.5 +/- 7.9 years; ppFEV1 53.7 +/- 21.0) completed the exercise program. Significant improvements were recorded from T0 to T1 (FB: p <= 0.05; PLR, OLS: p <= 0.01) and from T0 to T2 (FB, PLR p <= 0.01 and HE, OLS: p <= 0.05). W-peak, ppFEV1, BMI, and HPA showed no significant improvement between the single test points and over the entire study period (all p > 0.05). Conclusion. Our results show trainability of adults with CF in aspects of health-related and motor performance fitness during a partially supervised exercise program. Close supervision positively influences the results. Using a simple test setup seems to be a promising tool for evaluating the effects of exercise programs in CF and could serve as an additional outcome parameter in future clinical trials. Trial registration: ClinicalTrials.gov (retrospectively registered May 8, 2018).