Predictors of outcome in a contemporary cardiac sarcoidosis population: Role of brain natriuretic peptide, left ventricular function and myocardial inflammation

Aims Cardiac sarcoidosis (CS) is a potentially fatal condition that varies in its clinical presentation. Here, we describe baseline characteristics at presentation along with prognosis and predictors of outcome in a sizable and deeply phenotyped contemporary cohort of CS patients. Methods and results Consecutive CS patients seen at one institution were retrospectively enrolled after undergoing laboratory testing, electrocardiogram, echocardiography, cardiac magnetic resonance (CMR) imaging and $^{18}$F‐flourodeoxyglucose positron emission tomography (FDG‐PET) at baseline. The composite endpoint consisted of all‐cause mortality, aborted sudden cardiac death, major ventricular arrhythmic events, heart failure hospitalization and heart transplantation. A total of 319 CS patients were studied (67% male, 55.4 ± 12 years). During a median follow‐up of 2.2 years (range: 1 month–11 years), 8% of patients died, while 33% reached the composite endpoint. The annualized mortality rate was 2.7% and the 5‐ and 10‐year mortality rates were 6.2% and 7.5%, respectively. Multivariate analysis showed serum brain natriuretic peptide (BNP) levels (hazard ratio [HR] 2.41, 95% confidence interval [CI] 1.34–4.31, p = 0.003), CMR left ventricular ejection fraction (LVEF) (HR 0.96, 95% CI 0.94–0.98, p < 0.0001) and maximum standardized uptake value of FDG‐PET (HR 1.11, 95% CI 1.04–1.19, p = 0.001) to be independent predictors of outcome. These findings remained robust for different patient subgroups. Conclusion Cardiac sarcoidosis is associated with significant morbidity and mortality, particularly in those with cardiac involvement as the first manifestation. Higher BNP levels, lower LVEF and more active myocardial inflammation were independent predictors of outcomes

Pleuroparenchymal fibroelastosis in systemic sclerosis: prevalence and prognostic impact

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Diagnostic accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis: An international case-cohort study

We conducted an international study of idiopathic pulmonary fibrosis (IPF) diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts.A total of 1141 respiratory physicians and 34 IPF experts participated. Participants evaluated 60 cases of interstitial lung disease (ILD) without interdisciplinary consultation. Diagnostic agreement was measured using the weighted kappa coefficient (κw). Prognostic discrimination between IPF and other ILDs was used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the C-index.A total of 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (κw=0.65, IQR 0.53–0.72, p less than 0.0001) or physicians with access to multidisciplinary team (MDT) meetings (κw=0.54, IQR 0.45–0.64, p less than 0.0001). The prognostic accuracy of academic physicians with greater than 20 years of experience (C-index=0.72, IQR 0.0–0.73, p=0.229) and non-university hospital physicians with more than 20 years of experience, attending weekly MDT meetings (C-index=0.72, IQR 0.70–0.72, p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 IQR 0.72–0.75).Experienced respiratory physicians at university-based institutions diagnose IPF with similar prognostic accuracy to IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts

Real-world experience of nintedanib for progressive fibrosing interstitial lung disease in the UK

Background Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting.Methods 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022. Summary data regarding underlying diagnosis, pulmonary function tests, diagnostic criteria, radiological appearance, concurrent immunosuppressive therapy and drug tolerability were collected via electronic survey.Results 24 UK prescribing centres responded to the service evaluation invitation. Between 17 November 2021 and 30 September 2022, 1120 patients received a multidisciplinary team recommendation to commence nintedanib for PF-ILD. The most common underlying diagnoses were hypersensitivity pneumonitis (298 out of 1120, 26.6%), connective tissue disease associated ILD (197 out of 1120, 17.6%), rheumatoid arthritis associated ILD (180 out of 1120, 16.0%), idiopathic nonspecific interstitial pneumonia (125 out of 1120, 11.1%) and unclassifiable ILD (100 out of 1120, 8.9%). Of these, 54.4% (609 out of 1120) were receiving concomitant corticosteroids, 355 (31.7%) out of 1120 were receiving concomitant mycophenolate mofetil and 340 (30.3%) out of 1120 were receiving another immunosuppressive/modulatory therapy. Radiological progression of ILD combined with worsening respiratory symptoms was the most common reason for the diagnosis of PF-ILD.Conclusion We have demonstrated the use of nintedanib for the treatment of PF-ILD across a broad range of underlying conditions. Nintedanib is frequently co-prescribed alongside immunosuppressive and immunomodulatory therapy. The use of nintedanib for the treatment of PF-ILD has demonstrated acceptable tolerability in a real-world setting

High-resolution CT phenotypes in pulmonary sarcoidosis: a multinational Delphi consensus study

One view of sarcoidosis is that the term covers many different diseases. However, no classification framework exists for the future exploration of pathogenetic pathways, genetic or trigger predilections, patterns of lung function impairment, or treatment separations, or for the development of diagnostic algorithms or relevant outcome measures. We aimed to establish agreement on high-resolution CT (HRCT) phenotypic separations in sarcoidosis to anchor future CT research through a multinational two-round Delphi consensus process. Delphi participants included members of the Fleischner Society and the World Association of Sarcoidosis and other Granulomatous Disorders, as well as members' nominees. 146 individuals (98 chest physicians, 48 thoracic radiologists) from 28 countries took part, 144 of whom completed both Delphi rounds. After rating of 35 Delphi statements on a five-point Likert scale, consensus was achieved for 22 (63%) statements. There was 97% agreement on the existence of distinct HRCT phenotypes, with seven HRCT phenotypes that were categorised by participants as non-fibrotic or likely to be fibrotic. The international consensus reached in this Delphi exercise justifies the formulation of a CT classification as a basis for the possible definition of separate diseases. Further refinement of phenotypes with rapidly achievable CT studies is now needed to underpin the development of a formal classification of sarcoidosis

Προσβολή της καρδιάς στη σαρκοείδωση

Εισαγωγή: Η καρδιακή σαρκοείδωση σχετίζεται με αυξημένη νοσηρότητα και θνησιμότητα. Η μαγνητική τομογραφία καρδιάς αποτελεί βασική διαγνωστική εξέταση στην αξιολόγηση των ασθενών με καρδιακά συμπτώματα και υποψία της καρδιακής προσβολής, αλλά ο ακριβής ρόλος της μαγνητικής τομογραφίας καρδιάς σε σχέση με τις υπόλοιπες διαγνωστικές εξετάσεις για τη διάγνωση της καρδιακής σαρκοείδωση δεν έχει πλήρως καθοριστεί. Σκοπός: Να εκτιμηθεί η ανεξάρτητη και συλλογική διαγνωστική αξία των διαφόρων διαγνωστικών εξετάσεων για τη κλινική διάγνωση της καρδιακής σαρκοείδωση, να εκτιμηθεί ο ακριβής ρόλος της μαγνητικής τομογραφίας καρδιάς και να αναγνωριστούν οι ασθενείς που βρίσκονται σε υψηλότερο κίνδυνο εμφάνισης ανεπιθύμητων συμβάντων στο μέλλον. Μέθοδοι: Ασθενείς (n = 321) με ιστολογικά επιβεβαιωμένη σαρκοείδωση υποβλήθηκαν σε όλες τις απαραίτητες διαγνωστικές εξετάσεις συμπεριλαμβανομένου εκτίμησης των καρδιακών συμπτωμάτων, ηλεκτροκαρδιογράφημα, 24-ωρη ηλεκτροκαρδιογραφική παρακολούθηση με Holter και μαγνητική τομογραφία καρδιάς. Όλοι οι ασθενείς παρακολουθήθηκαν για εμφάνιση του πρωτεύοντος καταληκτικού σημείου (συνδυασμός θνησιμότητας από κάθε αιτία, συμπτωματικής απειλητικής για τη ζωή αρρυθμίας συμπεριλαμβανομένου επεισοδίων εμμένουσας κοιλιακής ταχυκαρδίας και ανάγκης μόνιμης βηματοδότησης, ή νοσηλείας για καρδιακή ανεπάρκεια) και του δευτερεύοντος καταληκτικού σημείου (επεισόδια μη εμμένουσας κοιλιακής ταχυκαρδίας). Αποτελέσματα: Καρδιακή σαρκοείδωση διαγνώστηκε στο 29,9% των ασθενών, με βάση κριτήρια των θέσεων ομοφωνίας της Εταιρείας Καρδιακού Ρυθμού. Η μαγνητική τομογραφία καρδιάς ήταν η πιο ευαίσθητη και ειδική δοκιμασία (AUC: 0,984) και κατάφερε να εντοπίσει 44 ασθενείς με καρδιακά συμπτώματα ή/και ηλεκτροκαρδιογραφικές αλλοιώσεις αλλά χωρίς διαταραχές στον υπέρηχο καρδιάς καθώς και 15 ασυμπτωματικούς ασθενείς χωρίς παθολογικά ευρήματα σε όλες τις άλλες διαγνωστικές εξετάσεις. Η προσθήκη του υπερήχου καρδιάς στη διαδικασία διαλογής με το καρδιολογικό ιστορικό και το ηλεκτροκαρδιογράφημα δεν άλλαξε την ευαισθησία της αρχικής στρατηγικής ελέγχου (αρχικά: 68,8% έναντι 72,9% μετά την προσθήκη). Παρά την υψηλή θετική προγνωστική αξία (83,9%), το υπερηχογράφημα καρδιάς είχε χαμηλή ευαισθησία (27,1%) για τη διάγνωση της καρδιακής σαρκοείδωσης. Κατά τη διάρκεια της παρακολούθησης, το 7,2% των ασθενών εμφάνισε το πρωτεύον καταληκτικό σημείο και άλλο ένα 3,4% το δευτερεύον καταληκτικό σημείο. Η καθυστερημένη ενίσχυση γαδολινίου στη μαγνητική τομογραφία καρδιάς ήταν ανεξάρτητος προγνωστικός δείκτης εμφάνισης του πρωτεύοντος καταληκτικού σημείου (HR 5.68, 95% CI: 1,74 - 18,49; P = 0,004). Η καθυστερημένη ενίσχυση γαδολινίου στη μαγνητική τομογραφία καρδιάς, η ηλικία, και ο εντοπισμός μη-εμμένουσας κοιλιακής ταχυκαρδίας στην αρχική 24-ωρη ηλεκτροκαρδιογραφική παρακολούθηση με Holter ήταν ανεξάρτητοι προγνωστικοί παράγοντες όλων των ανεπιθύμητων συμβάντων κατά τη διάρκεια της παρακολούθησης. Σε ασθενείς με καρδιακά συμπτώματα ή / και ηλεκτροκαρδιογραφικές αλλοιώσεις, η μαγνητική τομογραφία καρδιάς έδειξε αυξημένη διαγνωστική ακρίβεια και αποτέλεσε ανεξάρτητο προγνωστικό παράγοντα της εμφάνισης του πρωτεύοντος καταληκτικού σημείου. (HR: 12.71, 95% CI: 1,48 έως 109,35, p = 0,021). Συμπέρασμα: Από όλες τις διαγνωστικές εξετάσεις, η μαγνητική τομογραφία καρδιάς είναι η πιο πολύτιμη εξέταση για τη διάγνωση και την πρόγνωση της καρδιακής σαρκοείδωση στο γενικό πληθυσμό με ιστολογικά επιβεβαιωμένη σαρκοείδωση. Ο υπέρηχος καρδιάς έχει μια συνολικά περιορισμένη διαγνωστική αξία ως διαγνωστική εξέταση και διαταραχές στην εξέταση μπορεί να εξακολουθούν να χρειάζονται επιβεβαίωση με την διενέργεια μαγνητικής τομογραφίας καρδιάς, παρά την υψηλή θετική τους προγνωστική αξία.Background: Cardiac sarcoidosis is associated with increased morbidity and mortality. CMR is a key modality in the evaluation of patients with cardiac symptoms but the complementary role of CMR to conventional tests for the diagnosis of cardiac sarcoidosis is not fully defined. Objectives: To assess the independent and collective diagnostic value of various modalities in cardiac sarcoidosis, delineate the role of CMR and identify patients at risk. Methods: Patients (n=321) with biopsy-proven sarcoidosis underwent conventional cardiac testing and CMR with LGE and were followed up for primary (composite of all-cause mortality, sustained VT episodes or hospitalization for heart failure) and secondary (non-sustained VT episodes) endpoints. Results: Cardiac sarcoidosis was diagnosed in 29.9% of patients, based on HRS consensus criteria. CMR was the most sensitive and specific test (AUC: 0.984); it detected 44 patients with cardiac symptoms and/or ECG abnormalities but normal echocardiogram as well as 15 asymptomatic patients with normal baseline testing. Echocardiography added to cardiac history and ECG did not change sensitivity of the initial screening strategy (68.8% versus 72.9%). Despite a high positive predictive value (83.9%), echocardiography had a low sensitivity (27.1%). During follow-up, 7.2% of patients reached primary and another 3.4% secondary endpoint. LGE was independent predictor of primary endpoints (HR 5.68, 95%CI: 1.74–18.49; p=0.004). LGE, age, and baseline non-sustained VT were independent predictors of all events. In patients with cardiac symptoms and/or abnormal ECG, CMR increased diagnostic accuracy and independently predicted primary endpoints (HR: 12.71, 95%CI 1.48-109.35, p=0.021). Conclusion: Of all cardiac tests, CMR is the most valuable test in the diagnosis and prognosis of cardiac sarcoidosis in a general sarcoidosis population. Echocardiography has an overall limited diagnostic value as a screening test and an abnormal study, despite a high positive predictive value, may still need confirmation with CMR

Chemotherapy-induced neutropenia in lung cancer patients: The role of antibiotic prophylaxis

Chemotherapy-induced neutropenia can cause fatal bacterial infections. Colony-stimulating factors (CSFs) are usually recommended as prophylaxis, while routine use of prophylactic antibiotics remains controversial. Based on our literature search in PubMed, quinolones and trimethoprim/sulfamethoxazole were the most frequently used prophylaxis, while CSFs were administered in 22.1% of patients. Lung cancer patients who received prophylactic antibiotics exhibited significantly fewer episodes of febrile neutropenia, fewer documented infections as well as shorter duration of related hospitalisations. Prophylactic use of wide spectrum antibiotics seems effective and should be considered as an alternative strategy in the prevention of chemotherapy-induced neutropenia in lung cancer patients. (C) 2011 Elsevier Ireland Ltd. All rights reserved