Israel Medical Association Journal

Background: Heart failure (HF) patients with reduced ejection fraction (HFrEF) are frequently treated with sub-optimal doses of angiotensin converting enzyme-inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and beta blockers (BBs).

Objectives: To determine factors associated with attaining upper-range doses in patients with HFrEF.

Methods: We examined treatment in patients with left ventricular ejection fraction (LVEF) ≤ 40% in a community-based, dedicated heart-failure clinic. Upper-range doses were defined as ≥ 75% of target recommended doses by heart failure society guidelines.

Results: The majority of the 215 patients were men (82%); median age at presentation 73 years (interquartile range [IQR] 65–78) and LVEF of 30% (IQR 25–35%). Following the up-titration program, 41% and 35% of patients achieved upper-range doses of ACE-Is/ARBs and BBs, respectively. Higher body mass index (BMI) was the only parameter found to be associated with achieving upper-range doses of ACE-I/ARBs (odds ratio [OR] 1.13, 95% confidence interval [95%CI] 1.05–1.22, P = 0.001). More patients achieved this target as BMI increased, with a sharp decline in the highest obesity category (BMI ≥ 40 m²/kg). Attaining upper-range doses of BBs was associated with pre-existing diabetes mellitus (DM) (OR 2.6, 95%CI 1.34–5.19, P = 0.005); women were associated with attaining lower BBs doses (OR 0.34, 95%CI 0.13–0.90, P = 0.031).

Conclusions: Achieving upper-range doses of ACE-Is/ARBs and BBs in HFrEF outpatients in a treatment up-titration program were associated with greater BMI and DM, respectively. These findings may serve as benchmarks for up-titration programs.

Background: Metastatic melanoma is an aggressive and highly malignant cancer. The 5 year survival rate of patients with metastatic disease is less than 5% with a median survival of only 6–10 months. Drugs like dacarbazin (DTIC) as a single agent or in combination with other chemotherapy agents have a response rate of 15–30%, but the duration of response is usually short with no impact on survival. Interleukin-2-based immunotherapy has shown more promising results. The National Institutes of Health recently reported that lymphodepleting chemotherapy, followed by an adoptive transfer of large numbers of anti-tumor specific tumor-infiltrating lymphocytes, resulted in an objective regression in 51% of patients.

Objectives: To introduce the TIL[1] technology to advanced metastatic melanoma patients in Israel.

Methods: We generated TIL cultures from tumor tissue, choosing those with specific activity against melanoma and expanding them to large numbers.

Results: TIL cultures from nine patients were established and examined for their specific activity against the patients' autologous tumor cells. Twelve TIL cultures derived from 5 different patients showed the desired anti-tumor activity, making those 5 patients potential candidates for the therapy.

Conclusions: Pre-clinical studies of the TIL technology in a clinical laboratory set-up were performed successfully and this modality is ready for treating metastatic melanoma patients at the Sheba Medical Center's Ella Institute.