Quality of life, compliance, safety and effectiveness in fit older metastatic colorectal patients with cancer treated in first-line with chemotherapy plus cetuximab: A restrospective analysis from the ObservEr study

Abstract Objectives The influence of age ( KRAS wild type (WT) metastatic colorectal cancer (mCRC). Methods 225 patients of the Observed study (PS 0-1) were retrieved based on age ( Results The two patient groups (141  p  = 0.002), which is likely due to higher proportions of metastatic resection (27.0% vs 8.3%; p  = 0.001) and utilization of second-line therapy in younger group (58.9% vs 42.9%; p  = 0.028). Conclusion The current data suggest that fit older patients with mCRC can be safely treated with a cetuximab-based therapy, as QoL and safety profile do not seem to be affected by age. In addition, age did not impact the choice of chemotherapy to be associated to cetuximab and treatment compliance

Efficacy and safety of avelumab treatment in patients with metastatic Merkel cell carcinoma: experience from a global expanded access program

BackgroundAvelumab, a human anti–programmed death-ligand 1 immunoglobulin G1 monoclonal antibody, showed favorable efficacy and safety in patients with metastatic Merkel cell carcinoma (mMCC) in the phase II JAVELIN Merkel 200 trial, leading to approval in multiple countries. We describe real-world experience with avelumab in patients with mMCC from an expanded access program.MethodsEligible patients had mMCC and progressive disease during or after chemotherapy or were ineligible for chemotherapy or clinical trial participation. Patients received an initial 3-month supply of avelumab (administered as 10 mg/kg intravenously every 2 weeks until progressive disease or unacceptable toxicity); resupply was allowed following complete response, partial response, stable disease, or clinical benefit per physician assessment.ResultsBetween December 15, 2015, and March 4, 2019, 558 of 620 requests from 38 countries were medically approved, and 494 patients received avelumab. Among 240 evaluable patients, the objective response rate was 46.7% (complete response in 22.9%, including 3 of 16 potentially immunocompromised patients), and the disease control rate was 71.2%. The median duration of treatment in evaluable patients with response was 7.9 months (range, 1.0–41.7) overall and 5.2 months (range, 3.0–13.9) in immunocompromised patients. No new safety signals were identified. The expanded access program closed for new requests on December 31, 2018, as required after regulatory approval; benefitting patients continued to receive avelumab.ConclusionsThe avelumab expanded access program for patients with mMCC demonstrated efficacy and safety in a real-world setting, consistent with the results from JAVELIN Merkel 200, and provided a treatment for patients with limited options

Drag Force in a Charged N=4 SYM Plasma

Following recent developments, we employ the AdS/CFT correspondence to determine the drag force exerted on an external quark that moves through an N=4 super-Yang-Mills plasma with a non-zero R-charge density (or, equivalently, a non-zero chemical potential). We find that the drag force is larger than in the case where the plasma is neutral, but the dependence on the charge is non-monotonic.Comment: 16 pages, 1 eps figure; v2: references added, typos fixed; v3: more general ansatz, new nontrivial solution obtained, nonmonotonicity of the drag force made explicit in new figure, version to appear in JHE

Efficacy and safety of avelumab treatment in patients with metastatic Merkel cell carcinoma: experience from a global expanded access program

BackgroundAvelumab, a human anti–programmed death-ligand 1 immunoglobulin G1 monoclonal antibody, showed favorable efficacy and safety in patients with metastatic Merkel cell carcinoma (mMCC) in the phase II JAVELIN Merkel 200 trial, leading to approval in multiple countries. We describe real-world experience with avelumab in patients with mMCC from an expanded access program.MethodsEligible patients had mMCC and progressive disease during or after chemotherapy or were ineligible for chemotherapy or clinical trial participation. Patients received an initial 3-month supply of avelumab (administered as 10 mg/kg intravenously every 2 weeks until progressive disease or unacceptable toxicity); resupply was allowed following complete response, partial response, stable disease, or clinical benefit per physician assessment.ResultsBetween December 15, 2015, and March 4, 2019, 558 of 620 requests from 38 countries were medically approved, and 494 patients received avelumab. Among 240 evaluable patients, the objective response rate was 46.7% (complete response in 22.9%, including 3 of 16 potentially immunocompromised patients), and the disease control rate was 71.2%. The median duration of treatment in evaluable patients with response was 7.9 months (range, 1.0–41.7) overall and 5.2 months (range, 3.0–13.9) in immunocompromised patients. No new safety signals were identified. The expanded access program closed for new requests on December 31, 2018, as required after regulatory approval; benefitting patients continued to receive avelumab.ConclusionsThe avelumab expanded access program for patients with mMCC demonstrated efficacy and safety in a real-world setting, consistent with the results from JAVELIN Merkel 200, and provided a treatment for patients with limited options

Revalorization of barley straw and husk as precursors for cellulose nanocrystals extraction and their effect on PVA_CH nanocomposites

none8tPoly(vinyl alcohol) (PVA) blended with natural chitosan (CH) was selected as matrix for the production, bysolvent casting in water, of nanocomposite films containing cellulose nanocrystals (CNC) extracted frombarley residues, that were introduced in PVA CH systems as reinforcement phases. Cellulose nanocrys-tals were successfully extracted from both barley straw and husk by applying two different approaches, achemical alkaline and an enzymatic pre-treatment, followed by acidic hydrolysis. The results evidencedthe major effectiveness of the enzymatic pre-treatment on the quality of obtained CNC; nevertheless,all the different typologies of nanocrystals were added to the polymers and the morphological, optical,mechanical response, thermal and migration characteristics were investigated, whereas antimicrobialassay were carried out to evaluate the bactericidal effect induced by chitosan presence. The resultsindicated that chitosan reduced the optical transparency and the mechanical response of PVA matrix,whereas its combination with CNC (especially when extracted by enzymatic treatment and added at ahigher content) was able to modulate the optical properties, the mechanical and thermal responses. More-over, inhibitions on fungal and bacterial development were detected for PVA CH CNC ternary systems,suggesting their protective function against microorganisms contamination.mixedFORTUNATI, ELENA; BENINCASA, Paolo; Balestra, G. M.; LUZI, FRANCESCA; Mazzaglia, A.; DEL BUONO, Daniele; PUGLIA, Debora; TORRE, LuigiFortunati, Elena; Benincasa, Paolo; Balestra, G. M.; Luzi, Francesca; Mazzaglia, A.; DEL BUONO, Daniele; Puglia, Debora; Torre, Luig

Substitution of the arginine/leucine residues in apidaecin Ib with peptoid residues: effect on antimicrobial activity, cellular uptake, and proteolytic degradation.

Several aspects of the mechanism of action of Pro-rich antimicrobial peptides, together with their low toxicity in mammalian cells, make them good candidates for the development of new antibiotic agents. We investigated the effect induced in the insect antimicrobial peptide apidaecin Ib by the replacement of a single arginine/leucine residue with a N-substituted glycine. The resulting peptoid−peptide hybrids are more resistant to proteolysis and devoid of any significant cytotoxic activity, but moving the [NArg]residue from the N- to the C-terminal end of the molecule progressively reduces the antibacterial activity. Cell uptake experiments in E. coli cells suggest that the loss of antibacterial activity of [NArg17]apidaecin is a consequence of its inability to translocate into bacterial cells. Conversely, apidaecin and its peptoid−peptide hybrids are able to cross the plasma membrane in eukaryotic cells and to diffuse in the cytosol, although their translocating ability is far less effective than that of other known cell permeant peptides