The role of the immune response to oncolytic Herpes Simplex viral (oHSV) therapy for glioblastoma is controversial. Within hours of oHSV infection of human or syngeneic glioblastoma in mice, activated natural killer (NK) cells are recruited to the site of infection. This response significantly diminished the efficacy of glioblastoma virotherapy. oHSV-activated NK cells coordinated macrophage and microglia activation within tumors. In vitro, human NK cells preferentially lysed oHSV-infected human glioblastoma cell lines. This enhanced killing depended on NK cell natural cytotoxicity receptors (NCR) NKp30 and NKp46, whose ligands were up-regulated in oHSV-infected glioblastoma cells. HSV titers and oHSV efficacy were increased in Ncr1−/− mice and in a Ncr1−/− NK cell adoptive transfer model of glioma, respectively. These in vitro and in vivo (mouse) results demonstrate that glioblastoma virotherapy is partly limited by an antiviral NK cell response involving specific NCRs, uncovering novel potential targets to enhance cancer virotherapy.

Structured Abstract Background In a dynamic healthcare system, strong leadership has never been more important for surgeons. Little is known about how to effectively design and conduct a leadership program specifically for surgeons. We sought to critically evaluate a Leadership Development Program for practicing surgeons by exploring the strengths and weaknesses of program components on surgeons’ development as physician-leaders. Methods At a large academic institution, we conducted semi-structured interviews with 21 surgical faculty members who voluntarily applied, were selected, and completed a newly-created Leadership Development Program in December 2012. Interview transcripts underwent qualitative descriptive analysis with thematic coding based on grounded theory. Themes were extracted regarding surgeons’ evaluations of the program on their development as physician-leaders. Results After completing the program, surgeons reported personal improvements in the following 4 areas: self-empowerment to lead, self-awareness, team-building skills, and business and leadership knowledge. Surgeons felt “more confident about stepping up as a leader” and more aware about “how others view me and my interactions.” They described a stronger grasp on “giving feedback” as well as “business/organizational issues.” Overall, surgeon participants reported positive impacts of the program on their day-to-day work activities, general career perspective, as well as their long-term career development plans. Surgeons also recommended areas for potential improvement for the program. Conclusions These interviews detailed self-reported improvements in leadership knowledge and capabilities for practicing surgeons who completed a Leadership Development Program. A curriculum designed specifically for surgeons may enable future programs to better equip surgeons for important leadership roles in a complex healthcare environment.

IMPORTANCE Patient-generated health data captured from smartphone sensors have the potential to better quantify the physical outcomes of surgery. The ability of these data to discriminate between postoperative trends in physical activity remains unknown. OBJECTIVE To assess whether physical activity captured from smartphone accelerometer data can be used to describe postoperative recovery among patients undergoing cancer operations. DESIGN, SETTING, AND PARTICIPANTS This prospective observational cohort study was conducted from July 2017 to April 2019 in a single academic tertiary care hospital in the United States. Preoperatively, adults (age Ն18 years) who spoke English and were undergoing elective operations for skin, soft tissue, head, neck, and abdominal cancers were approached. Patients were excluded if they did not own a smartphone. EXPOSURES Study participants downloaded an application that collected smartphone accelerometer data continuously for 1 week preoperatively and 6 months postoperatively. MAIN OUTCOMES AND MEASURES The primary end points were trends in daily exertional activity and the ability to achieve at least 60 minutes of daily exertional activity after surgery among patients with vs without a clinically significant postoperative event. Postoperative events were defined as complications, emergency department presentations, readmissions, reoperations, and mortality. RESULTS A total of 139 individuals were approached. In the 62 enrolled patients, who were followed up for a median (interquartile range [IQR]) of 147 (77-179) days, there were no preprocedural differences between patients with vs without a postoperative event. Seventeen patients (27%) experienced a postoperative event. These patients had longer operations than those without a postoperative event (median [IQR], 225 [152-402] minutes vs 107 [68-174] minutes; P < .001), as well as greater blood loss (median [IQR], 200 [35-515] mL vs 25 [5-100] mL; P = .006) and more follow-up visits (median [IQR], 2 [2-4] visits vs 1 [1-2] visits; P = .002). Compared with mean baseline daily exertional activity, patients with a postoperative event had lower activity at week 1