Gavilimomab

Intratumoral immunotherapies are entering clinical use but concerns remain regarding their effects on non-injected tumors. Here, we studied the impact of local treatment with an adenovirus coding for TNFa and IL-2 on systemic antitumor response in animals receiving aPD-1 (anti-programmed cell death protein 1) therapy. Using bilateral murine melanoma models, we tested systemic tumor response to combined therapy with anti-PD-1 and an adenovirus coding for TNFa and IL-2 ("virus"). Virus was given intratumorally (to one of the two tumors only) and aPD-1 monoclonal antibody systemically. We evaluated both tumors' response to treatment, overall survival, metastasis development, and immunological mechanisms involved with response. Consistent tumor control was observed in both injected and non-injected tumors, including complete response in all treated animals receiving aPD-1+ virus therapy. Mechanistically, virus injections enabled potent effector lymphocyte response locally, with systemic effects in non-injected tumors facilitated by aPD-1 treatment. Moreover, adenovirus therapy demonstrated immunological memory formation. Virus therapy was effective in preventing metastasis development. Local treatment with TNFa and IL-2 coding adenovirus enhanced systemic response to aPD-1 therapy, by re-shaping the microenvironment of both injected and non-injected tumors. Therefore, our pre-clinical data support the rationale for a trial utilizing a combination of aPD-1 plus virus for the treatment of human cancer.

Compare the effectiveness of 1st-3rd generation cephalosporins (1st-3rdCE) to broad-spectrum antibiotics in decreasing surgical site infections (SSI) after pancreatectomy.

SSI is one of the most common complications after pancreatic surgery. Various antibiotic regimens are utilized nationwide with no clear guidelines for pancreatectomy. As we await results of a recently initiated prospective trial, this study retrospectively evaluates over 15,000 patients using the same administrative data abstraction tools as in the trial.

All relevant clinical variables were collected from the 2016–2018 targeted-pancreatectomy database from the American College of Surgeon National Surgical Quality Improvement Program. Preoperative antibiotics were initially collected as first-generation cephalosporin, second or third-generation cephalosporin, and broad-spectrum antibiotics (Broad-abx).

Of the 15,182 patients who completed a pancreatic surgery between 2016 and 2018, 6114 (40%) received a first-generation cephalosporin, 4097 (27%) received a second or third-generation cephalosporin, and 4971 (33%) received Broad-abx. On multivariate analysis, Broad-abx was associated with a decrease in all-type SSI compared to 1st-3rdCE (odds ratio = 0.73–0.77, P < 0.001) after open pancreaticoduodenectomy (PD). There was no difference in SSI between antibiotic-types after distal pancreatectomy. Subgroup multivariate analysis of open PD revealed decrease in all-type SSI with Broad-abx amongst patients with jaundice and/or biliary stent only, regardless of wound protector use (odds ratio = 0.69–0.70, P < 0.001). Propensity score matching of open PD patients with jaundice and/or biliary stent confirmed a decrease in all-type SSI (19% vs 24%, P = 0.001), and organ-space SSI (12% vs 16%, P < 0.001).

Broad-abx are associated with decreased SSI after open PD and may be preferred specifically for patients with preoperative biliary stent and/ or jaundice.