PURPOSE: To measure the effect of PIXY321 (granulocyte-macrophage colony-stimulating factor/interleukin-3 S. cerevisiae fusion protein) on the incidence, duration, and complications of neutropenia and thrombocytopenia after moderate-dose fluorouracil 600 mg/m², doxorubicin 60 mg/m², and cyclophosphamide 750 mg/m² (FAC) chemotherapy in patients with stage II and III breast cancer. PATIENTS AND METHODS: In this multicenter, randomized, double-blind placebo-controlled trial, 71 women were to receive four 21-day cycles of treatment with moderate-dose FAC chemotherapy by short intravenous infusion on day 1, followed by either placebo or PIXY321 (375 μg/m² subcutaneously twice a day) on days 3 to 15. All patients were to receive prophylactic oral ciprofloxacin when the absolute neutrophil count was less than 1,000/μL. RESULTS: PIXY321 significantly reduced the incidence and duration of grade 3 and grade 4 neutropenia in cycles 1 and 2 and the duration of grade 3 neutropenia in cycles 1 through 4. In cycles 3 and 4, grade 3 thrombocytopenia was significantly more common with PIXY321 (P < .05). Two patients, both in the PIXY321 group, required platelet transfusions. Fever and hospitalization for intravenous antibiotics were significantly more common in the PIXY321 group during cycle 1 only. More patients in the PIXY321 group achieved hematologic recovery by day 22 in cycles 1 through 3, and time to recovery was significantly shorter with PIXY321 in all cycles. FAC dose intensity was roughly 2% higher in the PIXY321 group (P = NS). Nonhematologic events of any intensity occurring with significantly greater overall frequency in the PIXY321 group included injection-site reactions, fever, chills, abdominal pain, and arthralgia. No patient died on study or within 30 days of her last dose of study drug. CONCLUSION: PIXY321 decreased the incidence and duration of FAC-induced grade 3 and 4 neutropenia in cycles 1 and 2 and significantly shortened the time to hematologic recovery in all cycles. However, it produced more systemic toxicity as well as thrombocytopenia in cycles 3 and 4.

Monitoring of geodynamic processes by modern GNSS techniques in the area of Sofia and South-Western Bulgaria has continued for 25 years. To study the modern crustal movements in the area, Global Positioning System (GPS) data acquired between 1996 and 2021 are analyzed to obtain the velocity field for South-Western Bulgaria. For a time period of almost 25 years, the monitoring has covered 28 stations. They have been measured in different years and in a number of campaigns. Despite the difference in the measurements, the obtained results are quite homogeneous in the different localities of the studied area and show clear uniform tendencies. All velocities are in the southern direction. They are in the range of 1.5 mm/year to slightly over 3 mm/year, almost reaching 4 mm/year. The velocities of the stations tend to increase from north (stations around Sofia), passing through an intermediate locality (between Sofia and Kyustendil–Pazardhik), clearly increasing in the southernmost part of the country (around Gotse Delchev). This velocity field motivates N–S expressed extension with increasing rates from North to South. The difference in the velocity rates tends to change along geologically suggested active fault zones. The obtained results generally confirm previously data, but with much better accuracy and details at the local level. This way, both the repeated measurements and extension of the geodynamic network prove to be a powerful tool for a better understanding of present-day geodynamics.

The territorial distribution of landslides along the Northern Bulgarian Black Sea coast has been evaluated by analyzing the results of field surveys for 2018 and 2019 based on geological surveys and processing of interferometric images from synthesized aperture radars (SAR). A local image archive of Sentinel-1A / B was created for the period 2015 - 2019 for this region and interferograms were produced every 4 months, 8 months, 1 year and in case of registering an event, led to the activation of landslide processes. A raster map of the concentration of deformations of the Earth's crust was created based on data from the obtained interferograms. Areas with active landslide movements along the Northern Bulgarian Black Sea coast have been identified for monitoring with the Global Navigation Satellite Systems (GNSS). A geodynamic network of 30 points covering the landslide circus ”Dalgiya Yar” and landslide “Thracian Cliffs“ was established and the first measurement cycle was carried out.