The Effect of Social Isolation on 1-Year Outcomes After Surgical Repair of Low-Energy Hip Fracture.

OBJECTIVES: To evaluate whether social isolation or loneliness is associated with outcomes 1 year after low-energy hip fracture. DESIGN: Prospective inception cohort study. SETTING: Academic level I trauma center. PATIENT SELECTION CRITERIA: Participants were 65 years or older and enrolled 2-4 days after surgery for a first low-energy hip fracture. Exclusion criteria were bilateral or periprosthetic hip fracture, previous hip fracture, non-English speaking, international address, active cancer, stage 4 cancer in the past 5 years, radiation to the hip region, and cognitive impairment. Participants were followed longitudinally for 1 year. OUTCOME MEASURES AND COMPARISONS: The patient-reported outcomes measurement information system (PROMIS)-29 was elicited 2-4 days postoperatively and 1 year later. Patient-reported risk factors included the Lubben Social Networks Scale and the University of California, Los Angeles Loneliness Scale, which were compared with the lower extremity activity scale and PROMIS-29 domains. RESULTS: Three hundred and twenty-five patients were enrolled. Participants had a median age of 81.7 years, were 70.9% female, and were 85.9% White. In total, 31.6% of patients were socially isolated at the time of fracture. At 1 year, 222 of the 291 subjects who were confirmed alive at 1 year provided data. Multivariable linear models were performed separately for each outcome, including lower extremity activity scale and PROMIS-29 domains. Controlling for age, sex, education, and body mass index, those who were socially isolated at the time of fracture had worse PROMIS-29 function (ß = -3.83; P = 0.02) and ability to participate in social roles (ß = -4.17; P = 0.01) at 1 year. Secondary analyses found that prefracture loneliness was associated with clinically meaningfully worse function, anxiety, depression, fatigue, sleep, pain, and ability to participate in social roles at 1 year (all P < 0.01). CONCLUSIONS: Prefracture social isolation was associated with worse outcomes 1 year after surgical repair of low-energy hip fracture. These data suggest loneliness may be more strongly associated with important patient-centric metrics than prefracture social isolation. Given the dearth of modifiable risk factors in this population, future studies are needed to evaluate whether improving social connections could affect outcomes in this rapidly growing demographic. LEVEL OF EVIDENCE: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.

Combination of autophagy inducer rapamycin and oncolytic adenovirus improves antitumor effect in cancer cells.

BACKGROUND: Combination of oncolytic adenoviruses (Ads) and chemotherapy drugs has shown promising therapeutic results and is considered as a potential approach for cancer therapy. We previously have shown that autophagy may generate decomposed cellular molecules that can be used as nutrition to support virus replication in cancer cells. In this study, we evaluated a unique combination of the novel oncolytic Ad-cycE with rapamycin, an autophagy inducer and first-line chemotherapeutic drug. METHODS: The combination of oncolytic Ad-cycE and the autophagy inducer rapamycin was assessed for enhanced antitumor effect. We also evaluated the combined effects of rapamycin and Ad-cycE on cancer cell viability. The interaction between Ad-cycE and rapamycin was analyzed with Calcusyn (Biosoft, Ferguson, MO). RESULTS: We show that rapamycin induces autophagy, enhances Ad E1A expression and increases Ad oncolytic replication. Combination of rapamycin and Ad-cycE elicits stronger cytotoxicity than single treatment alone. The analyzed data indicates that the Ad-cycE and rapamycin combination has a significantly synergistic antitumor effect. CONCLUSIONS: Our study provides a new insight into vector development and demonstrates the novel roles of autophagy in adenovirus replication. The combination of autophagy-induced chemotherapy and oncolytic virotherapy may be a new approach to improve future cancer treatment.