A soluble LAG-3 protein (eftilagimod alpha) and an anti-PD-L1 antibody (avelumab) tested in a phase I trial: a new combination in immuno-oncology.

BACKGROUND: Eftilagimod alpha (efti) is a major histocompatibility complex class II agonist activating antigen-presenting cells which leads to greater systemic type 1 T helper response and more cytotoxic CD8+ T-cell activation. This phase I trial evaluated the administration of efti, a soluble lymphocyte activation gene-3 (LAG-3) protein, combined with the anti-programmed death-ligand 1 (PD-L1) antibody avelumab in advanced solid tumors. PATIENTS AND METHODS: Patients with heavily pretreated metastatic solid tumors received intravenous avelumab (800 mg) combined with subcutaneously administered efti (6 or 30 mg) for up to 12 cycles, followed by avelumab monotherapy. The primary endpoint was the assessment of the recommended phase II dose (RP2D) of efti in combination with avelumab. RESULTS: Twelve patients with different tumor entities were enrolled (six patients in each cohort). During treatment, no dose-limiting toxicities occurred, and the severity of most adverse events was grade 1 or 2. In total, nine serious adverse events were documented, resulting in a fatal outcome in two cases, but none of them were assessed to be treatment related. Five patients (42%) achieved partial response. The median progression-free survival was 1.96 months and the median overall survival was not reached, with a 12-month survival rate of 75%. CONCLUSION: Subcutaneously administered efti plus avelumab was well tolerated, and efti of 30 mg was determined to be RP2D. The activity is promising and warrants further investigation in future phase II trials.

Fully differential molecular-frame measurements for the electron-impact dissociative ionization of H2.

We present fully differential state-resolved experimental data for the dissociative ionization of molecular hydrogen induced through electron impact. Molecular-frame ionization cross sections are derived for transitions from the X{1}Sigma{g}{+} molecular ground state to the 1ssigma{g}, 2psigma{u}, 2ssigma{g}, and 2ppi{u} states of H2+. For transitions to the 2ssigma{g} and 2ppi{u} states, a strong orientation dependence in the cross sections is revealed, with "side-on" preferred to "end-on" collisions and a propensity for the fragment proton to emerge along the normal to the scattering plane.

Role of miRNAs in the progression of malignant melanoma.

Analysis of microRNA (miRNA) biogenesis and function is an area of research that started only recently but has subsequently accelerated tremendously. This is because of the impressive impact of miRNA-mediated gene regulation and the obvious potential of those tiny RNA molecules in future diagnostic and therapeutic applications. In this review, recent progress to reveal the role of miRNAs in the tumourigenesis of malignant melanoma, as well as future prospects of melanoma-related miRNA research, will be addressed.

Treatment of painful skin ulcers with topical opioids.

Recent research suggests that opioid receptors on peripheral nerve terminals may play an important role in the modulation of pain. Clinical applications of this knowledge have been rather slow to evolve. We describe a consecutive series of nine patients with painful skin ulcers due to a variety of medical conditions. All patients were treated with a topical morphine-infused gel dressing. Seven of the nine patients experienced substantial and another experienced a lesser (but still significant) degree of analgesia. The ninth reported no relief, but his wound was not an open ulcer. Discussion centers on the practical application of this development in the large number of patients with painful skin lesions.

Dual-phase helical CT of the liver: effects of bolus tracking and different volumes of contrast material.

PURPOSE: To evaluate the effects of tracking and volume of contrast material on dual-phase helical computed tomography (CT) of the liver. MATERIALS AND METHODS: CT was performed in 120 consecutive patients. Either 100 mL (groups 1 and 2) or 120 mL (groups 3 and 4) of contrast material was injected at a rate of 4 mL/sec. In groups 1 and 3, the scanning delay was fixed, whereas in groups 2 and 4, scanning delays were determined individually by means of a semiautomatic bolus tracking device. The arterial phase began when splenic enhancement was greater than 10 HU and ended when hepatic enhancement was greater than 20 HU, which characterized the start of the portal venous phase. RESULTS: The mean duration of the arterial phase was 11.6 (100 mL) and 12.2 seconds (120 mL). The arterial phase of the liver within the defined limits was sufficiently timed in only 16 (54%) patients in group 1, 25 (83%) in group 2, and 20 (67%) in groups 3, whereas it was significantly (P < .05) better in 28 (93%) patients in group 4. A significantly (P < .05) higher mean parenchymal enhancement in the portal venous phase (63.6 HU +/- 8.5) was obtained in group 4. CONCLUSION: Bolus tracking of a volume of 120 mL provided the most accurate results in dual-phase liver CT.