The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1–2) and 57 (11.3%) as serious (grade 3–5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.

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Background: The aim of the present study was to identify specious radiologic and/or physiologic prognostic marker(s), which lead to optimize of the patient follow-up frequency. Methods: Eighty consecutive patients with newly diagnosed pulmonary sarcoidosis. Patients underwent chest radiography, high-resolution computed tomography (HRCT) examination, pulmonary function tests (PFT), bronchoscopy with bronchoalveolar lavage (BAL) and lung biopsy, and bronchoalveolar lavage fluid (BALF) cell examination. Results: The reduction in PFT values seen in radiological sarcoidosis stage III was greater than that seen in stages I and II. The percentage of neutrophils in the lungs was found to increase in stages II and III. PFT indices were correlated negatively with the consolidation and ground glass opacities CT scores, but not with the micronodule or macronodule scores. The rise in the percentage of BALF lymphocytes was associated with the restriction pattern of PFT. The diagnostic value of BALF for sarcoidosis was higher when the typical radiologic patterns of stage I disease were found and that smoking decreased the diagnostic value of CD4/CD8 ratio. Conclusions: This study supports the opinion that the staging of the pulmonary sarcoidosis with chest X-rays is still valuable from the prognostic point of view, because significant correlations between the radiologic stages of sarcoidosis and PFT parameters were found. Chest HRCT was significantly superior to chest X-ray in detecting mediastinal and pulmonary parenchymal changes. However, the prognostic role of HRCT needs to be better investigated evaluating serial examinations. Only consolidation and ground glass scores (neither of which are frequently found in sarcoidosis) hold prognostic value, since these were negatively correlated with PFT parameters.

Background: The mechanisms driving the transition from inflammation to fibrosis in sarcoidosis patients are poorly understood; prognostic features are lacking. Immune cell profiling may provide insights into pathogenesis and prognostic factors of the disease. This study aimed to establish associations in simultaneous of lymphocyte subset profiles in the blood, bronchoalveolar lavage fluid (BALF), and lung biopsy tissue in the patients with newly diagnosed sarcoidosis.Methods: A total of 71 sarcoid patients (SPs) and 20 healthy controls (HCs) were enrolled into the study. CD31, CD38, CD44, CD103 positive T lymphocytes in blood and BALF were analysed. Additionally, the densities of CD4, CD8, CD38, CD44, CD103 positive cells in lung tissue biopsies were estimated by digital image analysis. Results: Main findings: (I) increase of percentage of CD3 + CD4 + CD38 + in BALF and blood, and increase of percentage of CD3 + CD4 + CD44 + in BALF in Löfgren syndrome patients comparing with patients without Löfgren syndrome, (II) increase of percentage of CD3 + CD4 + 103 + in BALF and in blood in patients without Löfgren syndrome (comparing with Löfgren syndrome patients) and increase of percentage of CD3 + CD4 + 103 + in BALF and in blood in more advanced sarcoidosis stage. (III) Increasing percentage of BALF CD3 + CD4 + CD31 + in sarcoidosis patients when comparing with controls independently of presence of Löfgren syndrome, smoking status or stage of sarcoidosis. Several significant correlations were found. Conclusions: Lymphocyte subpopulations in blood, BALF, and lung tissue were substantially different in SPs at the time of diagnosis compared to HCs. CD3 + CD4 + CD31 + in BALF might be a potential supporting marker for the diagnosis of sarcoidosis. CD3 + CD4 + CD38 + in BALF and blood and CD3 + CD4 + CD44 + in BALF may be markers of the acute immune response in sarcoidosis patients. CD4 + CD103 + T-cells in BALF and in blood are markers of the persistent immune response in sarcoidosis patients and are potential prognostic features of the chronic course of this disease.