Trauma patients produce a host of danger signals and high levels of damage-associated molecular patterns (DAMPs) after cellular injury and tissue damage. These DAMPs are directly and indirectly involved in the pathogenesis of various inflammatory and thrombotic complications in patients with severe injuries. No effective therapeutic agents for the removal of DAMPs from blood or tissue fluid have been developed. Herein, we demonstrated that nucleic acid binding polymers, e.g., polyethylenimine (PEI) and polyamidoamine dendrimers, immobilized onto electrospun microfiber mesh can effectively capture various DAMPs, such as extracellular DNAs and high mobility group box 1 (HMGB1). Furthermore, treatment with PEI-immobilized microfiber mesh abrogated the ability of DAMPs, released from dead and dying cells in culture or found in patients following traumatic injury, to activate innate immune responses and coagulation in vitro and in vivo. Nucleic acid scavenging microfiber meshes represent an effective strategy to combat inflammation and thrombosis in trauma.

Lessons Learned. Due to evolving imaging criteria in brain tumors and variation in magnetic resonance imaging evaluation, it is not ideal to use response rate as a primary objective. Future studies involving antiangiogenic agents should use overall survival.Disease‐expected toxicities should be considered when defining the clinical significance of an adverse event. For example, vascular thromboembolic events are common in brain tumor patients and should not be attributed to the study drug in the safety analysis.Background.Recurrent malignant glioma (rMG) prognosis is poor, with a median patient survival of 3–11 months with bevacizumab (BEV)‐containing regimens. BEV in rMG has 6‐month progression free survival (PFS‐6) of ∼40% and an objective response rate of 21.2%. BEV‐containing regimens improve PFS‐6 to 42.6%–50.3%, indicating that BEV combination therapies may be superior to single agent. Rilotumumab, a hepatocyte growth factor (HGF) antibody, inhibits angiogenesis and expression of angiogenic autocrine factors (e.g., vascular endothelial growth factor [VEGF]) by c‐Met inhibition. Combination of rilotumumab with BEV to block vascular invasion and tumor proliferation may synergistically inhibit tumor growth.Methods.Thirty‐six BEV‐naïve rMG subjects received rilotumumab (20 mg/kg and BEV (10 mg/kg) every 2 weeks. Endpoints included objective response rate (using Response Assessment in Neuro‐Oncology [RANO] criteria), PFS‐6, overall survival (OS), and toxicity.Results.Median patient follow‐up was 65.0 months. Objective response rate was 27.8% (95% confidence interval [CI]: 15.7%–44.1%). Median OS was 11.2 months (95% CI: 7–17.5). PFS‐6 was 41.7% (95% CI: 25.6%–57.0%). Most frequent treatment‐related grade ≤2 events included weight gain, fatigue, allergic rhinitis, and voice alteration; grade ≥3 events included venous thromboembolism (four patients), including one death from pulmonary embolism.Conclusion.Rilotumumab with BEV did not significantly improve objective response compared with BEV alone, and toxicity may preclude the use of rilotumumab in combination BEV regimens.

Background Overall survival (OS) in glioblastoma (GBM) is poor at an average of 14 to 18 months, and long-term survivors (LTS) of GBM are rare. LTS of GBM, defined as surviving >5 years postdiagnosis, represent only 2% to 10% of all GBM patients. LTS of cancer are at high risk of developing second primary neoplasms. This study looks at occurrences of second primary neoplasms in LTS of GBM. Methods Records from adult patients newly diagnosed with GBM between January 1, 1998 and February 8, 2010, were retrospectively reviewed to identify LTS, defined as patients who survived ≥5 years. We focused on the identification of a new diagnosis of cancer occurring at least 2 years after the initial GBM diagnosis. Results We identified 155 LTS of GBM, with a median OS of 11.0 years (95% CI: 9.0 to 13.1 years) and a median follow-up of 9.6 years (95% CI: 8.7 to 10.7 years). In this cohort of patients, 13 (8.4%) LTS of GBM developed 17 secondary cancers. Eight could potentially be attributed to previous radiation and chemotherapy (skin cancer in radiation field [n = 4], leukemia [n = 2], low-grade glioma [n = 1], and sarcoma of the scalp [n = 1]). The other 9 cases included melanoma (n = 2), prostate cancer (n = 2), bladder cancer (n = 1), endometrioid adenocarcinoma (n = 1), basal cell carcinoma (n = 1), and renal cell carcinoma (n = 1). Conclusions Although second primary cancers are rare in GBM LTS, providers should continue close monitoring with appropriate oncologic care. Moreover, this highlights the need for survivorship care of patients with GBM.

Dying cells release nucleic acids (NA) and NA-containing complexes that activate inflammatory pathways of immune cells. Sustained activation of these pathways contributes to chronic inflammation frequently encountered in autoimmune and inflammatory diseases. In this study, grafting of cationic polymers onto a nanofibrous mesh enabled local scavenging of negatively charged pro-inflammatory molecules in the extracellular space. Nucleic acid scavenging nanofibers (NASFs) formed from poly(styrene-alt-maleic anhydride) conjugated with 1.8 kDa bPEI resulted in nanofibers of diameters 486 ± 9 nm. NASFs inhibited the NF-κB response stimulated by the negatively charged agonists, CpG and poly(I:C), in Ramos-blue cells but not Pam3CSK4, a nonanionic agonist. Moreover, NASFs significantly impeded NF-κB activation in cells stimulated with damage-associated molecular pattern molecules (DAMPs) released from doxorubicin killed cancer cells. In vivo application of NASFs to open wounds demonstrated nucleic acid scavenging in wounds of diabetic mice infected with Pseudomonas aeruginosa, suggesting the in vivo efficacy of NASFs. This simple technique of generating NASF results in effective localized anti-inflammation in vitro and local nucleic acid scavenging in vivo.