Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

TOURIST INDUSTRY GROWTH PRESSURE ALONG THE BULGARIAN BLACK SEA COAST

Abstract Coastal zone representing the boundary between sea and land is a highly dynamical and sensitive area that comprises a large variety of natural resources. Population growth in the littoral causes rapid urbanization of the coast, development of infrastructures, transport system and so on. Therefore, coastal ecosystems experience pressure and become vulnerable to pollution, habitat degradation and loss, overfishing, and increased coastal hazards. Accelerated tourism development during the recent years is an extra risk factor for the Bulgarian Black Sea coastal zone. Considering that the coastal zone is a limited and very vulnerable land area, the high population increase due to tourism is one of the most hazardous factors for coastal zone sustainability. Although tourism growth and coastal development give rise to a number of economic benefits, they also could lead to loss of habitat, green space, and biodiversity

TOURIST INDUSTRY GROWTH PRESSURE ALONG THE BULGARIAN BLACK SEA COAST

Abstract Coastal zone representing the boundary between sea and land is a highly dynamical and sensitive area that comprises a large variety of natural resources. Population growth in the littoral causes rapid urbanization of the coast, development of infrastructures, transport system and so on. Therefore, coastal ecosystems experience pressure and become vulnerable to pollution, habitat degradation and loss, overfishing, and increased coastal hazards. Accelerated tourism development during the recent years is an extra risk factor for the Bulgarian Black Sea coastal zone. Considering that the coastal zone is a limited and very vulnerable land area, the high population increase due to tourism is one of the most hazardous factors for coastal zone sustainability. Although tourism growth and coastal development give rise to a number of economic benefits, they also could lead to loss of habitat, green space, and biodiversity

Types and impacts of maritime hydraulic structures on the Romanian – Bulgarian Black Sea coast: setting-up a common catalogue for GIS-based coastline classification

Abstract: The present study is a basic part of developing a joint GIS-based coastline typology to determine various geomorphic types of landforms (natural/ anthropogenic) along the Western Black Sea coast. The main purpose is to develop a web geomorphic classification for this part of the Black Sea coast, covering both Bulgaria and Romania. The research is focused on inventory the multipurpose maritime hydraulic constructions (harbour and coastprotection types) built along the Bulgarian-Romanian coast and to point out on their functions and effects. Setting-up of a common catalogue to all types of maritime structures for the Bulgarian-Romanian part of the Western Black Sea coast will help the establishment of unified technical terminology. The results are an important step to create a common classification criteria based on geomorphologic and engineering research approaches for identifying natural landforms and technogenous objects along the both coastlines

First results from the releases of Cinereous Vultures (Aegypius monachus) aiming at re-introducing the species in Bulgaria – the start of the establishment phase 2018–2022

The current work presents the preliminary results of the Cinereous Vulture (Aegypius monachus) releases in the Balkan Mountains in 2018–2022, aiming at the species re-introduction in Bulgaria, where it was listed as locally extinct since 1985. The first imports and releases of Cinereous Vultures in Bulgaria started in 2018. Until mid-2022, 72 individuals were released in the Eastern Balkan Mountains (Kotlenska Planina SPA and Sinite Kamani Nature Park) and Vrachanski Balkan Nature Park. Of them, 63 immatures imported from Spain were released from aviaries and nine juveniles captive-bred in European zoos were released by hacking (fledging from an artificial nest). We compared the success in survival and establishment between the different release sites and methods used to adjust the ongoing technics and tactics and to support knowledge improvement for future similar projects.From the nine Cinereous Vultures released by hacking, the results were as follows: 1.00 fledging success, but only 0.22 survival in the first six months – combined period of acclimation, first migration and the first winter. All survivors from that period reached maturity into the wild, but all emigrated from the release site and settled elsewhere.Of the 63 individuals released by aviaries, 32 individuals were released in the Eastern Balkan Mountains (18 individuals are still alive – 0.56 survival; 14 individuals settled in the area, which accounts for 0.44 of all released birds and 0.78 of the survivors). Thirty-one individuals were released in Vrachanski Balkan Nature Park (23 individuals are still alive – 0.74 survival; 22 individuals settled in the area – 0.71 of all released birds and 0.96 of the survivors). Based only on aviary method comparison, the settling of the individuals in the release area was alike in the two sites. However, the Vrachanski Balkan Nature Park performed better in survival – both in acclimation and establishment periods.While comparing the release methods – hacking and release from the aviary – the following results were observed: the survival rate during acclimation was 0.86. Due to more considerable losses during the first migration and dispersal in the individuals released by hacking, the survival rate of 0.22 was significantly lower compared to 0.73 for the birds released from the aviary. Additionally, in both methods, a similar pattern in the first winter and spring migration dispersal was observed. Although the survival was equal in the released-by-hacking or aviary birds after the first year onwards, it is essential to note that the emigration of the hacked birds from the release site was 1.00. In comparison, the birds released from aviaries largely remained and settled in the release area (&amp;gt; 0.77 of the survivors). The cost of release and related acclimation, settling, dispersal and the first winter was the greatest: 0.12–0.17 per period, or cumulatively, it was about 0.27. Survival increased and stabilised to &amp;gt; 0.90 after the first year in the wild and reached nearly 1.00 after two years in the wild onwards.Two distinct nuclei of the Cinereous Vulture were established along the Balkan Mountains – the Eastern Balkan Mountains with 18–23 individuals and four formed pairs using a territory of about 642.74 km2 – 95% home range and 85.72 km2 – 50% core area with center being the town of Kotel; and Vrachanski Balkan Nature Park with present 23–29 individuals, of which 2–3 pairs formed so far, using a territory of about 1,143.66 km2 – 95% home range and 22.89 km2 – 50% core area with center being the village of Zgorigrad. The species readily accepted breeding in artificial nest platforms built by professional arborists on different tree species – oak, beech, sycamore and pine. The only naturally built nests were on the ground (n = 2) (unsuccessful) and in Scots Pine (n = 1) (successful). In 2021 and 2022, in each of the two sites, the first successful reproductions were recorded, which marked the return of the Cinereous Vulture as breeding species – 28 years after the last occasional record of a single breeding pair in the country and 36 years after it was officially listed as locally extinct in Bulgaria

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk