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7015 Background: Ruxolitinib (RUX), a Janus kinase (JAK) 1/2 inhibitor, is the current standard of care for patients (pts) with myelofibrosis (MF) that improves splenomegaly and disease symptoms with limited impact on disease biology. Many pts lose response over time, highlighting an unmet need for novel therapies. Navitoclax (NAV) is an oral, small-molecule inhibitor of BCL-XL and BCL-2 that has a synergistic effect when used in combination with JAK inhibitors to enhance apoptosis. This ongoing, open-label, multicenter, phase 2 trial (NCT03222609) is evaluating the efficacy and safety of NAV with/without RUX in pts with MF. Here, we report results from JAK inhibitor-naïve pts treated with NAV+RUX. Methods: Enrolled pts had primary or secondary MF with splenomegaly (DIPSS ≥INT-1) and did not receive prior JAK-2 therapy or bromodomain and extraterminal motif (BET) inhibitors. Pts initiated NAV at 100 mg QD or 200 mg QD if baseline (BL) platelet count was ≤150 × 109/L or >150 × 109/L, respectively. RUX was given BID with starting dose based on BL platelet count per local label. The primary endpoint was spleen volume reduction of ≥35% (SVR35) from BL at wk 24. Key secondary endpoints were ≥50% reduction in total symptom score (TSS50), bone marrow (BM) fibrosis reduction, and anemia response. Adverse events (AEs) were monitored throughout the study. Results: As of Oct 04, 2021, 32 pts received NAV+RUX. Median duration of f/u was 6.1 (range, 1.9 ─ 18.6) mos. 28 (88%) pts received NAV 200 mg and 4 (13%) received 100 mg OD. Median age was 69 (44 ─ 83) yrs, and median spleen volume was 1889.08 cm3 (645.6 ─ 7339.6). Median NAV and RUX exposures were 24.1 (5.1 ─ 80.9) and 20.1 (0.1 ─ 80.1) wks, respectively. 31 (97%) pts reported ≥1 AE (Grade ≥3 AEs, 25 [78%]; serious AEs, 6 [19%]). Most common Grade ≥3 AEs were anemia (34%), thrombocytopenia (31%), and neutropenia (19%). 3 (9%) and 2 (6%) pts reported an AE leading to NAV and RUX discontinuation, respectively, and 2 (6%; 1 PD, 1 cardiac disorder unrelated to NAV) AEs led to death ≤30 days after last NAV dose. SVR35 was achieved by 52% of evaluable pts at wk 24 (SVR35 in INT-2, 50%; HR, 33%) and by 76% at any time on treatment (Table). Median time to first SVR35 was 12.1 (11 ─ 47) wks. Conclusions: The combination of NAV+RUX was well tolerated and demonstrated early and robust reductions in spleen volume, anemia, and BM fibrosis in pts without prior JAK-2 inhibitor exposure. SVR35, TSS50, and BM fibrosis improved over time. Clinical trial information: NCT03222609. [Table: see text]

The beam-ion interaction is one of the potential limitations of beam performance in ultra-low emittance electron rings. The High Energy Photon Source (HEPS), under construction in Beijing, is one example for which the beam-ion effect has to be carefully evaluated. In this paper, we will introduce the beam-ion interaction models applied in HEPS. Based on these models, a new numerical simulation code is developed. Currently, the code includes modules such as ionization, beam-ion interaction, synchrotron radiation damping, quantum excitation, bunch-by-bunch feedback etc. Settings such as weak-strong, strong-strong and arbitrary number of interaction points can be launched in the code. It will be shown that the beam instability excited by the beam-ion interaction can be effectively suppressed by the bunch-by-bunch feedback system., CERN Yellow Reports: Conference Proceedings, Vol. 9 (2020): Proceedings of the ICFA mini-Workshop on Mitigation of Coherent Beam Instabilities in Particle Accelerators, Zermatt, Switzerland, 23–27 September 2019

Background Acupuncture therapy is well known. But there is no report that acupuncture in patients with coagulation dysfunction in stroke may lead to severe soft tissue injury. we report a case of acupuncture leading to severe soft tissue injury.Methods A 63-year-old female patient was hospitalized for stroke rehabilitation. After 2 years of discharge, severe subcutaneous hematoma caused by acupuncture was readmitted to hospital. She received medication and physical rehabilitation. we monitored the international standardized ratio (INR) in plasma and observed the degree of dissipation of subcutaneous hematoma. the changes of patients during treatment were explored by data analysis.Findings Subcutaneous hematoma (area 20×20 cm) disappeared completely after 3 weeks of physical factor therapy. Small range (area ≤3×3 cm) subcutaneous hematoma can heal itself within 2 weeks. Improper acupuncture is only one of the causes of soft tissue injury. Stroke with coagulation dysfunction is not a contraindication of acupuncture treatment.Interpretation Our report suggests that previously unanticipated acupuncture treatment for stroke patients with coagulation dysfunction may lead to severe multiple soft tissue injuries. Although coagulation dysfunction is not a contraindication of acupuncture treatment, acupuncture treatment for stroke patients with coagulation dysfunction should be vigilant, strengthen the level of acupuncture operation, and fundamentally eliminate the problem. These cases are validation and supplement of adverse clinical reactions caused by improper acupuncture.