Phillyrin sensitizes lung cancer cells to ferroptosis through inhibiting FTH1/SLC7A11 axis.

Ferroptosis is a newly found form of non-apoptotic regulated cell death that is essential for cancer progression. Phillyrin (PHN), an effective lignan glycoside of Forsythia suspensa, has been explored as a potential anticancer agent in some cancer types. However, it is unclear whether and how PHN could promote the death of non-small cell lung cancer (NSCLC) cells by inducing ferroptosis. Our study showed for the first time that PHN induced cell death and attenuated cell proliferation in NSCLC cells in vitro and in vivo. Functional assays showed that ferroptosis was the predominant form that contributed to PHN-induced cell death of NSCLC cells. Mechanistically, NSCLC cells exposed to PHN had a decreased ferritin heavy chain 1 (FTH1) and SLC7A11 protein expression. Exogenetic overexpression of FTH1 substantially abrogated the tumor-inhibiting effects of PHN and further upregulated the expression of SLC7A11 in NSCLC cells. In conclusion, our findings suggest that the natural product PHN exerted its antitumor activity in NSCLC by promoting ferroptosis, and the FTH1/SLC7A11 axis plays an indispensable role in PHN-induced ferroptotic cell death.

Patient Engagement and Cost Savings Achieved by Automated Telemonitoring Systems Designed to Prevent and Identify Surgical Site Infections After Joint Replacement.

BACKGROUND: We designed two telemonitoring text and voice messaging interventions, EpxDecolonization (EpxDecol) and EpxWound, to improve management of orthopedic joint replacement patients at Washington University. We reviewed the use of these tools for a period of 88 weeks. METHODS: Cohorts of 1,392 and 1,753 participants completed EpxDecol and EpxWound, respectively. All patients who completed EpxDecol also completed EpxWound. We assessed patient use of and satisfaction with these interventions. A return on investment (ROI) analysis was conducted to determine the cost savings generated by EpxWound and EpxDecol. RESULTS: The proportions of patients who responded daily to EpxDecol and EpxWound were 91.9% and 77.7%, respectively, over the lengths of each intervention. The percent of daily responders declined <5% during each intervention. Ultimately, 88.4% of EpxDecol patients and 67.8% of EpxWound patients responded to ≥80% of all messages. Median patient survey responses (n = 1,246) were 9/9 (best possible) for care, 8/9 for improved communication, and 5/9 (perfect number) for number of messages received. ROI analysis for this 88-week period showed that using EpxDecol and EpxWound to engage patients (instead of nurses calling patients) saved the equivalent of 2.275 full-time nursing equivalents per week. We calculated net savings of $260,348 with an ROI of 14.85x for 1,753 patients over 88 weeks. One-year cost savings from these interventions were $153,800 with an ROI of 14.79x. CONCLUSIONS: EpxDecol and EpxWound may serve important roles in the perioperative process for orthopedic joint reconstruction surgery given high patient usage of and satisfaction with these interventions. Implementing EpxDecol and EpxWound for a large patient population could yield substantial cost savings and ROI.

Use of Short Message Service and Smartphone Applications in the Management of Surgical Patients: A Systematic Review.

BACKGROUND: Mobile health and telemedicine are rapidly evolving fields used to provide healthcare remotely to patients. For surgical patients, telemedicine can improve patient education and remote monitoring of postoperative symptoms. We performed a systematic review of studies involving the use of short message service (SMS) and mobile application-based interventions in surgical patients to evaluate the advantages and disadvantages of each system, as well as of mobile interventions as a whole. MATERIALS AND METHODS: Major electronic databases were searched using relevant keywords from inception until November 2016. Studies involving SMS or mobile application-based communication protocols involving at least 25 preoperative or postoperative patients were included. Studies of systems involving communication exclusively between healthcare professionals were excluded. RESULTS: A total of 2,492 unique studies were identified through keyword search. After applying inclusion and exclusion criteria, 15 studies were included in this review. Intervention modalities were SMS (8 studies), mobile application (4), combined SMS and application (1), automated phone call (1), and electronic transmission of pictures to the physician (1). Intervention methods were symptom monitoring (7), patient education (2), protocol adherence reminders (4), and combined symptom monitoring and protocol adherence reminders (2). Both mobile applications and SMS-based interventions increased adherence to medications and protocols and improved clinic attendance. Lower readmission rates and emergency room visits were reported. Satisfaction with automated communication systems was high for both patients and physicians. CONCLUSIONS: Mobile interventions provide a sophisticated yet simple tool to improve perioperative healthcare. Future considerations to address include usage fatigue and Health Insurance Portability and Accountability Act compliance concerns.

Non-spreading Bessel spatiotemporal optical vortices.

Non-spreading nature of Bessel spatiotemporal wavepackets is theoretically and experimentally investigated and orders of magnitude improvement in the spatiotemporal spreading has been demonstrated. The spatiotemporal confinement provided by the Bessel spatiotemporal wavepacket is further exploited to transport transverse orbital angular momentum through embedding spatiotemporal optical vortex into the Bessel spatiotemporal wavepacket, constructing a new type of wavepacket: Bessel spatiotemporal optical vortex. Both numerical and experimental results demonstrate that spatiotemporal vortex structure can be well maintained and confined through much longer propagation. High order spatiotemporal optical vortices can also be better confined in the spatiotemporal domain and prevented from further breaking up, overcoming a potential major obstacle for future applications of spatiotemporal vortex.

Combined Orthopaedic and Vascular Injuries With Ischemia: A Multicenter Analysis.

OBJECTIVES: To review a large, multicenter experience to identify the current salvage and amputation rates of these combined injuries and, where possible, the variables that predict amputation. DESIGN: Retrospective. SETTING: Nine trauma centers. PATIENTS: This study involved 199 patients presenting to 9 trauma centers with orthopaedic and vascular injuries resulting in ischemic limbs for whom the orthopaedic service was involved with the decision for salvage versus amputation. RESULTS: We reviewed 199 patients, 17-85 years of age. One hundred seventy-two of the injuries were open. Thirty-eight patients (19%) were treated with amputation upon admission as they were deemed to be unsalvageable. Of the remaining 161 patients who had attempted salvage, 36 (30%) required late amputation. Closed injuries were successfully salvaged in 25 of 27 cases (93%). The highest rate of amputation was in tibia fractures with a combined amputation rate of 62%. In those attempted to be salvaged, 21 of 48 (44%) required amputation. The ischemia time for successful salvage was significantly less, P = 0.03. One hundred twenty-four patients had their definitive vascular repair before the bony reconstruction. There were 15 vascular complications, of which 13 (86%) had the definitive vascular repair performed before the definitive osseous repair, although this was not statistically significant. CONCLUSIONS: In this series of combined orthopaedic and vascular injuries, we found a high rate of acute and late amputations. It is possible that other protocols, such as shunting and stabilizing the osseous injury, before vascular repair may benefit limb salvage, although this needs more study. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Sleep disturbances in orthopaedic trauma patients.

OBJECTIVES: To determine the prevalence of sleep disturbances in orthopaedic trauma patients 3 months following surgery and to identify any subset(s) of patients at high risk for prolonged sleep disturbance. DESIGN: Prospective cohort. SETTING: Level 1 Trauma Center. PATIENT/PARTICIPANTS: All patients at an orthopaedic trauma clinic from May 3, 2016 to Feb 23, 2017. MAIN OUTCOME MEASUREMENTS: Baseline patient Pittsburgh Sleep Questionnaire (PSQI) and Insomnia Severity Index (ISI) scores compared to PSQI and ISI scores 3-months postoperatively. Both gender and age stratified data analyses were performed. RESULTS: Sixty-six patients met our inclusion criteria and completed both baseline and 3-month surveys. There were 44 males and 22 females. There was a significant increase in PSQI and ISI scores from baseline to 3 months across all patients. Further analysis revealed significant increases from baseline to 3 months in both PSQI and ISI scores for female patients but not male patients. There was a significant difference from baseline to 3 months in patients 50 years old and under but not for patients above 50 years old. No patients required revision surgery in the first 3 months. CONCLUSIONS: More than half of all patients reported continued sleep disturbance 3 months postoperatively. Females are at particularly increased risk for sleep disturbance. These findings demonstrate that sleep disturbances merit attention in the early stages of the postoperative recovery process. LEVEL OF EVIDENCE: Therapeutic Level II.

Accessible Communication Tools for Surgical Site Infection Monitoring and Prevention in Joint Reconstruction: Feasibility Study.

BACKGROUND: The National Surgical Quality Improvement Program logs surgical site infections (SSIs) as the most common cause of unplanned postoperative readmission for a variety of surgical interventions. Hospitals are making significant efforts preoperatively and postoperatively to reduce SSIs and improve care. Telemedicine, defined as using remote technology to implement health care, has the potential to improve outcomes across a wide range of parameters, including reducing SSIs. OBJECTIVE: The purpose of this study was to assess the feasibility and user satisfaction of two automated messaging systems, EpxDecolonization and EpxWound, to improve perioperative care in a quality improvement project for patients undergoing total joint replacement. METHODS: We designed two automated text messaging and calling systems named EpxDecolonization, which reminded patients of their preoperative decolonization protocol, and EpxWound, which monitored pain, wound, and fever status postoperatively. Daily patient responses were recorded and a post-usage survey was sent out to participants to assess satisfaction with the systems. RESULTS: Over the 40-week study period, 638 and 642 patients were enrolled in EpxDecolonization (a preoperative decolonization reminder) and EpxWound (a postoperative surgical site infection telemonitoring system), respectively. Patients could be enrolled in either or both EpxDecolonization and EpxWound, with the default option being dual enrollment. The proportion of sessions responded to was 85.2% for EpxDecolonization and 78.4% for EpxWound. Of the 1280 patients prescribed EpxWound and EpxDecolonization, 821 (64.14%) fully completed the postoperative system satisfaction survey. The median survey score (scale 1-9) was 9 for patient-rated overall care and 8 for whether the telemonitoring systems improved patient communication with providers. The majority of patients (69.0%, 566/821) indicated that the systems sent out an ideal number of messages (not too many, not too few). CONCLUSIONS: EpxDecolonization and EpxWound demonstrated high response rates and improved patient-rated communication with providers. These preliminary data suggest that these systems are well tolerated and potentially beneficial to both patients and providers. The systems have the potential to improve both patient satisfaction scores and compliance with preoperative protocols and postoperative wound monitoring. Future efforts will focus on testing the sensitivity and specificity of alerts generated by each system and on demonstrating the ability of these systems to improve clinical quality metrics with more authoritative data.