Objective. Atrial fibrillation (AF) in type 2 diabetes mellitus (T2DM) has been little explored so far. However, there are several cardio metabolic risk factors for AF in T2DM patients, such as arterial hypertension, obesity or the metabolic syndrome. Our objective was to evaluate cardio metabolic risk factors for AF in T2DM patients. Methods. We studied the medical records of T2DM patients hospitalized in the Internal Medicine department of an emergency referral hospital in Bucharest, Romania. The study was observational, retrospective and carried out between January-June 2018. Results. The study group included 221 T2DM patients (with a mean age of 68.65 ± 10.64, ranging between 37-93 years): 116 women (52.49%; with a mean age of 70.53 ± 10.69, ranging between 37-93 years) and 105 men (47.51%; with a mean age of 66.57 ± 10.23, ranging between 38-91 years). 92 patients had AF (41.63%): 40 women (34.48%) and 52 men (49.52%). 180 patients (81.45%) were hypertensive: 103 women (88.79%) and 77 men (73.33%). 113 patients (51.13%) had metabolic syndrome: 58 women (50.00%) and 55 men (52.38%). 77 patients (34.84%) were obese: 45 women (38.79%) and 32 men (30.48%). AF patients associated obesity in 26 cases (28.26%), hypertension in 73 cases (79.35%) and metabolic syndrome in 56 cases (60.87%). Conclusions. Out of the study group, 92 T2DM patients (41.63%) had AF, men being more likely to suffer from AF than women (p=0.0288). Hypertension affected 180 patients (81.45%) and in greater proportion women vs. men (p=0.0051). The metabolic syndrome and obesity were discovered in 113 patients (51.13%) and 77 patients (34.84%), respectively, with no significant differences in terms of gender. In our research, the highest cardio metabolic risk factors for AF in T2DM were hypertension (OR = 3.6675) and the metabolic syndrome (OR = 3.3388).

In the past decades, the involvement of reactive oxygen species (ROS) in health and disease has been intensely studied. Apart from their antimicrobial role in phagocytosis, ROS are also involved in a multitude of cellular processes, such as cell cycle progression, cellular motility or amplification of signaling factors. Many diseases are characterized by an overproduction of ROS or by deficient antioxidant systems, thus leading to oxidative stress (OxS) onset. The involvement of OxS in several types of solid cancers (prostate cancer, breast cancer, colorectal cancer and melanoma) and hematological malignancies (acute lymphoblastic leukemia, myelodysplastic syndromes, acute and chronic myeloid leukemia) has been proved. Recent studies have hypothesized that ROS derived from tumors can promote cell survival, migration, metastasis, proliferation and even drug-resistance according to the origin of the cancer. However, the involvement of OxS in carcinogenesis is far from being completely understood.

Chronic myeloid leukemia (CML) is a chronic myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome. Oxidative stress is involved in CML etiopathogenesis and disease progression, as well as the response to tyrosine kinase inhibitors (TKI) treatment. We evaluated oxidative stress levels in 47 CML patients vs. controls. The total antioxidant capacity (TAC) was measured using a FLUOstar Omega microplate reader (reagents from Sigma-Aldrich). Cellular reactive oxygen species (ROS) were evaluated using a CyFlow SPACE Sysmex flow-cytometer (reagents from Abcam). Oxidative stress levels were higher in CML patients vs. controls. The maximum TAC value and the minimum ROS value were recorded in CML patients with a BCR-ABL1 transcript value of 0.1-1%, suggesting that the production of plasma antioxidants progressively increases as a compensatory mechanism in CML patients undergoing TKI treatment in order to annihilate ROS. The pseudonormalization of the cell redox status observed in these patients could be an alarm signal prior to the development of resistance to TKI treatment or disease progression.

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mg/d, 5 patients receiving 30 mg/d and 1 patient receiving 45 mg/d. The other 6 patients were receiving either 15 mg every other day (n = 4), 15 mg 4 times or 3 times a week (n = 1), or alternating 30 mg and 15 mg every other day (n = 1). Subsequently, in the POST-PACE study, the median PON additional treatment duration was 24.1 months (10.8-29.8) and the median daily dose of PON was increased to 18.8 mg (5.0-37.5). A sustained at least MMR was observed for 5 patients and achieved for 1 more; 3 patients were in MCyR and the others sustained CHR. Only one MMR loss was reported during POST-PACE following a dose decrease from 30 mg/d to 15 mg/d in a patient with MMR by the end of PACE. Overall, the median PON treatment duration across PACE and POST-PACE studies was 82.4 months (range, 68.7-88.8). Moreover, overall survival was 100% at data cut-off as no death was recorded. Regarding safety, 44 adverse events (AE) were reported including 8 vascular occlusive events (VOE) related to PON in 7 patients: 1 arterial lower limb disorder, 2 hypertensions, 2 subclavian artery stenoses (1 bilateral), 1 gut ischemia, and 1 arterial stenosis and 1 thrombosis occurring in the same patient. VOE were mostly managed by dose adaptation or treatment discontinuation (1 patient). Among AEs, 6 occurring in 4/16 (25%) patients were considered as serious, including 5 VOE: the arterial stenosis, the thrombosis, the gut ischemia (at 7.5 mg/d) and the 2 subclavian artery stenosis (at 15 mg/d and 45 mg/d). Summary/Conclusion: In summary, this first interim analysis of POST-PACE indicates that PON yields durable responses over an extended period of almost 7 years and that dose management adapted to each patient is warranted to maintain efficacy while controlling tolerability in heavily pre-treated CP-CML patients.