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Poly ADP-ribose polymerase inhibitors (PARPi) are first-line maintenance therapy for ovarian cancer and an alternative therapy for several other cancer types. However, PARPi-resistance is rising and there is currently an unmet need to combat PARPi-resistant tumors. Here, we created an immunocompetent, PARPi-resistant mouse model to test the efficacy of combinatory PARPi and euchromatic histone methyltransferase 1/2 inhibitor (EHMTi) in the treatment of PARPi-resistant ovarian cancer. We discovered that inhibition of EHMT1/2 resensitizes cells to PARPi. Markedly, we show that single EHMTi and combinatory EHMTi/PARPi significantly reduced PARPi-resistant tumor burden and that this reduction is partially dependent on CD8 T cells. Altogether, our results show a low-toxicity drug that effectively treats PARPi-resistant ovarian cancer in an immune-dependent manner, supporting its entry into clinical development and potential incorporation of immunotherapy. Implications: Targeting the epigenome of therapy-resistant ovarian cancer induces an anti-tumor response mediated in part through an anti-tumor immune response.

Introduction: Occlusion after infra-inguinal bypass surgery for peripheral artery disease is a major complication with potentially devastating consequences. In this descriptive analysis, we sought to describe the natural history and explore factors associated with long-term major amputation-free survival following occlusion of a first-time infra-inguinal bypass., Methods: Using a prospective database from a tertiary care vascular center, we conducted a retrospective cohort study of all patients with peripheral artery disease who underwent a first-time infra-inguinal bypass and subsequently suffered a graft occlusion (1997-2021). The primary outcome was longitudinal rate of major amputation-free survival after bypass occlusion. Cox proportional hazard models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) to explore predictors of outcomes., Results: Of the 1318 first-time infra-inguinal bypass surgeries performed over the study period, 255 bypasses occluded and were included in our analysis. Mean age was 66.7 (12.6) years, 40.4% were female, and indication for index bypass was chronic limb threatening ischemia (CLTI) in 89.8% (n = 229). 48.2% (n = 123) of index bypass conduits used great saphenous vein, 29.0% (n = 74) prosthetic graft, and 22.8% (n = 58) an alternative conduit. Median (interquartile range) time to bypass occlusion was 6.8 (2.3-19.0) months, and patients were followed for median of 4.3 (1.7-8.1) years after bypass occlusion. Following occlusion, 38.04% underwent no revascularization, 32.94% graft salvage procedure, 25.1% new bypass, and 3.92% native artery recanalization. Major amputation-free survival following occlusion was 56.9% (50.6%-62.8%) at 1 y, 37.1% (31%-43.3%) at 5 y, and 17.2% (11.9%-23.2%) at 10 y. In multivariable analysis, factors associated with lower amputation-free survival were older age, female sex, advanced cardiorenal comorbidities, CLTI at index procedure, CLTI at time of occlusion, and distal index bypass outflow. Initial treatment after occlusion with both a new surgical bypass (HR 0.44, CI: 0.29-0.67) or a graft salvage procedure (HR 0.56, CI: 0.38-0.82) showed improved amputation-free survival. One-year rate of major amputation or death were 59.8% (50.0%-69.6%) for those who underwent no revascularization, 37.9% (28.7%-49.0%) for graft salvage, and 26.7% (17.6%-39.5%) for new bypass., Conclusions: Long-term major amputation-free survival is low after occlusion of a first-time infra-inguinal bypass. While several nonmodifiable risk factors were associated with lower amputation-free survival, treatment after graft occlusion with either a new bypass or a graft salvage procedure may improve longitudinal outcomes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Chromobox 2 (CBX2), an epigenetic reader and component of polycomb repressor complex 1, is highly expressed in >75% of high-grade serous carcinoma. Increased CBX2 expression is associated with poorer survival, whereas CBX2 knockdown leads to improved chemotherapy sensitivity. In a high-grade serous carcinoma immune-competent murine model, knockdown of CBX2 decreased tumor progression. We sought to explore the impact of modulation of CBX2 on the tumor immune microenvironment (TIME), understanding that the TIME plays a critical role in disease progression and development of therapy resistance. Exploration of existing datasets demonstrated that elevated CBX2 expression significantly correlated with specific immune cell types in the TIME. RNA sequencing and pathway analysis of differentially expressed genes demonstrated immune signature enrichment. Confocal microscopy and co-culture experiments found that modulation of CBX2 leads to increased recruitment and infiltration of macrophages. Flow cytometry of macrophages cultured with CBX2-overexpressing cells showed increased M2-like macrophages and decreased phagocytosis activity. Cbx2 knockdown in the Trp53-null, Brca2-null ID8 syngeneic murine model (ID8 Trp53-/-Brca2-/-) led to decreased tumor progression compared with the control. NanoString immuno-oncology panel analysis suggested that knockdown in Cbx2 shifts immune cell composition, with an increase in macrophages. Multispectral immunohistochemistry (mIHC) further confirmed an increase in macrophage infiltration. Increased CBX2 expression leads to recruitment and polarization of protumor macrophages, and targeting CBX2 may serve to modulate the TIME to enhance the efficacy of immune therapies., Significance: CBX2 expression correlates with the TIME. CBX2 modulation shifts the macrophage population, potentially leading to an immunosuppressive microenvironment, highlighting CBX2 as a target to improve efficacy of immunotherapy., (©2024 The Authors; Published by the American Association for Cancer Research.)

Cancer cells exhibit rewired transcriptional regulatory networks that promote tumor growth and survival. However, the mechanisms underlying the formation of these pathological networks remain poorly understood. Through a pan-cancer epigenomic analysis, we found that primate-specific endogenous retroviruses (ERVs) are a rich source of enhancers displaying cancer-specific activity. In colorectal cancer and other epithelial tumors, oncogenic MAPK/AP1 signaling drives the activation of enhancers derived from the primate-specific ERV family LTR10. Functional studies in colorectal cancer cells revealed that LTR10 elements regulate tumor-specific expression of multiple genes associated with tumorigenesis, such as ATG12 and XRCC4 . Within the human population, individual LTR10 elements exhibit germline and somatic structural variation resulting from a highly mutable internal tandem repeat region, which affects AP1 binding activity. Our findings reveal that ERV-derived enhancers contribute to transcriptional dysregulation in response to oncogenic signaling and shape the evolution of cancer-specific regulatory networks.

Despite the success of poly-ADP-ribose polymerase inhibitors (PARPi) in the clinic, high rates of resistance to PARPi presents a challenge in the treatment of ovarian cancer, thus it is imperative to find therapeutic strategies to combat PARPi resistance. Here, we demonstrate that inhibition of epigenetic modifiers euchromatic histone lysine methyltransferases 1/2 (EHMT1/2) reduces the growth of multiple PARPi-resistant ovarian cancer cell lines and tumor growth in a PARPi-resistant mouse model of ovarian cancer. We found that combinatory EHMT and PARP inhibition increases immunostimulatory double-stranded RNA formation and elicits several immune signaling pathways in vitro. Using epigenomic profiling and transcriptomics, we found that EHMT2 is bound to transposable elements, and that EHMT inhibition leads to genome-wide epigenetic and transcriptional derepression of transposable elements. We validated EHMT-mediated activation of immune signaling and upregulation of transposable element transcripts in patient-derived, therapy-naïve, primary ovarian tumors, suggesting potential efficacy in PARPi-sensitive disease as well. Importantly, using multispectral immunohistochemistry, we discovered that combinatory therapy increased CD8 T-cell activity in the tumor microenvironment of the same patient-derived tissues. In a PARPi-resistant syngeneic murine model, EHMT and PARP inhibition combination inhibited tumor progression and increased Granzyme B+ cells in the tumor. Together, our results provide evidence that combinatory EHMT and PARP inhibition stimulates a cell autologous immune response in vitro, is an effective therapy to reduce PARPi-resistant ovarian tumor growth in vivo, and promotes antitumor immunity activity in the tumor microenvironment of patient-derived ex vivo tissues of ovarian cancer., (©2024 American Association for Cancer Research.)

Multidrug efflux transporters are major contributors to the antibiotic resistance of Acinetobacter baumannii in clinical settings. Previous studies showed that these transporters are tightly integrated into the physiology of A. baumannii and have diverse functions. However, for many of the efflux pumps, such functions remain poorly defined. In this study, we characterized two putative drug efflux pumps, AmfAB and AmfCD (Acinetobacter Major Facilitator), that are homologous to EmrAB-like transporters from Escherichia coli and other Gram-negative bacteria. These pumps comprise the Major Facilitator Superfamily (MFS) transporters AmfB and AmfD and the periplasmic membrane fusion proteins AmfA and AmfC, respectively. We inactivated and overproduced these pumps in the wild-type ATCC 17978 strain and its derivative strains lacking the major efflux pumps from the Resistance-Nodulation-Division (RND) superfamily and characterized antibiotic susceptibilities and growth of the strains under stresses typical during human infections. We found that neither AmfAB nor AmfCD contribute to the antibiotic non-susceptibility phenotypes of A. baumannii. The two pumps, however, are critical for the adaptation and growth of the bacterium under acidic stress, whereas AmfCD also contributes to growth under conditions of low iron, high temperature, and in the presence of bile salts. These functions are dependent on the presence of the RND pumps, the inactivation of which further diminishes A. baumannii survival and growth. Our results suggest that MFS transporters contribute to stress survival by affecting the permeability properties of the A. baumannii cell envelope.

Li 1.5 Al 0.5 Ge 1.5 (PO 4 ) 3 (LAGP) is a promising oxide solid electrolyte for all-solid-state batteries due to its excellent air stability, acceptable electrochemical stability window, and cost-effective precursor materials. However, further improvement in the ionic conductivity performance of oxide solid-state electrolytes is hindered by the presence of grain boundaries and their associated morphologies and composition. These key factors thus represent a major obstacle to the improved design of modern oxide based solid-state electrolytes. This study establishes a correlation between the influence of the grain boundary phases, their 3D morphology, and compositions formed under different sintering conditions on the overall LAGP ionic conductivity. Spark plasma sintering has been employed to sinter oxide solid electrolyte material at different temperatures with high compacity values, whereas a combined potentiostatic electrochemical impedance spectroscopy, 3D FIB-SEM tomography, XRD, and solid-state NMR/materials modeling approach provides an in-depth analysis of the influence of the morphology, structure, and composition of the grain boundary phases that impact the total ionic conductivity. This work establishes the first 3D FIB-SEM tomography analysis of the LAGP morphology and the secondary phases formed in the grain boundaries at the nanoscale level, whereas the associated 31 P and 27 Al MAS NMR study coupled with materials modeling reveals that the grain boundary material is composed of Li 4 P 2 O 7 and disordered Li 9 Al 3 (P 2 O 7 ) 3 (PO 4 ) 2 phases. Quantitative 31 P MAS NMR measurements demonstrate that optimal ionic conductivity for the LAGP system is achieved for the 680 °C SPS preparation when the disordered Li 9 Al 3 (P 2 O 7 ) 3 (PO 4 ) 2 phase dominates the grain boundary composition with reduced contributions from the highly ordered Li 4 P 2 O 7 phases, whereas the 27 Al MAS NMR data reveal that minimal structural change is experienced by each phase throughout this suite of sintering temperatures.

Organic-inorganic halide perovskites are interesting candidates for solar cell and optoelectronic applications owing to their advantageous properties such as a tunable band gap, low material cost, and high charge carrier mobilities. Despite making significant progress, concerns about material stability continue to impede the commercialization of perovskite-based technology. In this article, we investigate the impact of environmental parameters on the alteration of structural properties of MAPbI 3 (CH 3 NH 3 PbI 3 ) thin films using microscopy techniques. These characterizations are performed on MAPbI 3 thin films exposed to air, nitrogen, and vacuum environments, the latter being possible by using dedicated air-free transfer setups, after their fabrication into a nitrogen-filled glovebox. We observed that even less than 3 min of air exposure increases the sensitivity to electron beam deterioration and modifies the structural transformation pathway as compared to MAPbI 3 thin films which are not exposed to air. Similarly, the time evolution of the optical responses and the defect formation of both air-exposed and non-air-exposed MAPbI 3 thin films are measured by time-resolved photoluminescence. The formation of defects in the air-exposed MAPbI 3 thin films is first observed by optical techniques at longer timescales, while structural modifications are observed by transmission electron microscopy (TEM) measurements and supported by X-ray photoelectron spectroscopy (XPS) measurements. Based on the complementarity of TEM, XPS, and time-resolved optical measurements, we propose two different degradation mechanism pathways for air-exposed and non-air-exposed MAPbI 3 thin films. We find that when exposed to air, the crystalline structure of MAPbI 3 shows gradual evolution from its initial tetragonal MAPbI 3 structure to PbI 2 through three different stages. No significant structural changes over time from the initial structure are observed for the MAPbI 3 thin films which are not exposed to air., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

This paper describes the effective fabrication of an inverse opal (IO) structure for plasmon-induced hyperthermia applications using silver nanoparticles (AgNPs) doped in a conducting polymer of poly(3,4-ethylene dioxythiophene) (PEDOT). Indium tin oxide (ITO) substrates were firstly modified electrochemically by a layer of the inverse opal structure of PEDOT (IO-PEDOT). These as-prepared electrodes were subsequently used as working electrodes for electrodepositing AgNPs. The presence of plasmonic AgNPs doped inside a polymer network caused the hybrid of IO-PEDOT and AgNPs to generate significantly more heat than thin-film PEDOT, thin-film PEDOT/AgNPs, and IO-PEDOT under 532 nm laser irradiation. This is attributed to the synergistic effect of the large active area inverse opal structure and doped AgNPs, which exhibit more thermal energy and heat faster than the individual component structures. These findings point to a wide range of potential applications for hybrid IO-PEDOT/AgNPs in hyperthermia treatment., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

High-grade serous ovarian cancer (HGSOC) is the deadliest ovarian cancer histotype due in-part to the lack of therapeutic options for chemotherapy-resistant disease. PARP inhibitors (PARPi) represent a targeted treatment. However, PARPi resistance is becoming a significant clinical challenge. There is an urgent need to overcome resistance mechanisms to extend disease-free intervals. We established isogeneic PARPi-sensitive and -resistant HGSOC cell lines. In three PARPi-resistant models, there is a significant increase in AP-1 transcriptional activity and DNA repair capacity. Using RNA-sequencing and an shRNA screen, we identified activating transcription factor 6 (ATF6) as a mediator of AP-1 activity, DNA damage response, and PARPi resistance. In publicly available datasets, ATF6 expression is elevated in HGSOC and portends a poorer recurrence-free survival. In a cohort of primary HGSOC tumors, higher ATF6 expression significantly correlated to PARPi resistance. In PARPi-resistant cell lines and a PDX model, inhibition of a known ATF6 regulator, p38, attenuated AP-1 activity and RAD51 foci formation, enhanced DNA damage, significantly inhibited tumor burden, and reduced accumulation of nuclear ATF6., Implications: This study highlights that a novel p38-ATF6-mediated AP-1 signaling axis contributes to PARPi resistance and provides a clinical rationale for combining PARPi and AP-1 signaling inhibitors., (©2022 American Association for Cancer Research.)

Objective: Despite the emergence of endovascular aneurysm repair (EVAR) as the most common approach to abdominal aortic aneurysm repair, open aneurysm repair (OAR) remains an important option. This study seeks to define the indications for OAR in the EVAR era and how these indicatioxns effect outcomes., Methods: A retrospective cohort study was performed of all OAR at a single institution from 2004 to 2019. Preoperative computed tomography scans and operative records were assessed to determine the indication for OAR. These reasons were categorized into anatomical contraindications, systemic factors (connective tissue disorders, contraindication to contrast dye), and patient or surgeon preference (patients who were candidates for both EVAR and OAR). Perioperative and long-term outcomes were compared between the groups., Results: We included 370 patients in the analysis; 71.6% (265/370) had at least one anatomic contraindication to EVAR and 36% had two or more contraindications. The most common anatomic contraindications were short aortic neck length (51.6%), inadequate distal seal zone (19.2%), and inadequate access vessels (15.7%). The major perioperative complication rate was 18.1% and the 30-day mortality was 3.0%. No single anatomic factor was identified as a predictor of perioperative complications. Sixty-one patients (16.5%) underwent OAR based on patient or surgeon preference; these patients were younger, had lower incidences of coronary artery disease and chronic obstructive pulmonary disease, and were less likely to require suprarenal cross-clamping compared with patients who had anatomic and/or systemic contraindications to EVAR. The patient or surgeon preference group had a lower incidence of perioperative major complications (8.2% vs 20.1%; P = .034), shorter length of stay (6 days vs 8 days; P < .001) and no 30-day mortalities. The multivariable adjusted risk for 15-year mortality was lower for patient or surgeon preference patients (adjusted hazard ratio, 0.44; 95% confidence interval, 0.24-0.80; P = .007) compared with those anatomic or systemic contraindications., Conclusions: Within a population of patients who did not meet instruction for use criteria for EVAR, no single anatomic contraindication was a marker for worse outcomes with OAR. Patients who were candidates for both aortic repair approaches but elected to undergo OAR owing to patient or surgeon preference have very low 30-day mortality and morbidity, and superior long-term survival rates compared with those patients who underwent OAR owing to anatomic and/or systemic contraindications to EVAR., (Published by Elsevier Inc.)

Importance: Prior publications have reported the sporadic development of sensorineural hearing loss (SNHL) after intravenous or high-dose macrolide therapy for adults with comorbid conditions, but investigations of the auditory effect of oral outpatient dosing for children, adolescents, and young adults have been limited., Objective: To determine whether broad-based outpatient use of oral macrolide therapy is associated with increased risk of pediatric SNHL through nationally representative analyses., Design, Setting, and Participants: A retrospective case-control study of 875 matched pairs of children, adolescents, and young adults was performed, matching on age, sex, and the time elapsed since prescription date. All eligible pediatric patients were included, with matched control participants from the TRICARE US military health insurance system who were evaluated between October 1, 2009, and September 30, 2014., Exposures: Oral outpatient macrolide treatment compared with penicillin use among pediatric patients., Main Outcomes and Measures: The clinical outcome of interest was SNHL in children, adolescents, and young adults. Multivariable conditional logistic regression was used to compare the risk of prior macrolide exposure with penicillin exposure, adjusted for other risk factors and potential confounders. Four time frames between exposure and diagnosis were additionally assessed., Results: There were 875 eligible matched pairs of children, adolescents, and young adults included. The mean (SD) age of the participants was 5.7 (4.9) years; 1082 participants were male (62%), 58 were Asian (3%), 254 were Black (15%), 1152 were White (66%), and 286 were of Native American and other (no further breakdown was available in the TRICARE database) race and ethnicity (16%). In multivariable analysis, participants who had SNHL had increased odds of having received a macrolide prescription compared with a penicillin prescription when all time frames from exposure were included (adjusted odds ratio, 1.31; 95% CI, 1.05-1.64). There were significantly higher odds of macrolide exposure than penicillin exposure when diagnosis and testing occurred more than 180 days after antibiotic exposure (adjusted odds ratio, 1.79; 95% CI, 1.23-2.60)., Conclusions and Relevance: In this case-control study of a nationally representative patient population, findings suggest that children, adolescents, and young adults with SNHL had increased odds of outpatient oral macrolide use compared with penicillin use, particularly when having received a diagnosis more than 180 days after exposure. Further study of the association of macrolides with SNHL in children, adolescents, and young adults is warranted.

Background: Confounding by indication is a serious threat to comparative studies using real world data. We assessed the utility of automated data-adaptive analytic approach for confounding adjustment when both claims and clinical registry data are available., Methods: We used a comparative study example of carotid artery stenting (CAS) vs. carotid endarterectomy (CEA) in 2005-2008 when CAS was only indicated for patients with high surgical risk. We included Medicare beneficiaries linked to the Society for Vascular Surgery's Vascular Registry >65 years old undergoing CAS/CEA. We compared hazard ratios (HRs) for death while adjusting for confounding by combining various 1) Propensity score (PS) modeling strategies (investigator-specified [IS-PS] vs. automated data-adaptive [ada-PS]); 2) data sources (claims-only, registry-only and claims-plus-registry); and 3) PS adjustment approaches (matching vs. quintiles-adjustment with/without trimming). An HR of 1.0 was used as a benchmark effect estimate based on CREST trial., Results: The cohort included 1,999 CAS and 3,255 CEA patients (mean age 76). CAS patients were more likely symptomatic and at high surgical risk, and experienced higher mortality (crude HR = 1.82 for CAS vs. CEA). HRs from PS-quintile adjustment without trimming were 1.48 and 1.52 for claims-only IS-PS and ada-PS, 1.51 and 1.42 for registry-only IS-PS and ada-PS, and 1.34 and 1.23 for claims-plus-registry IS-PS and ada-PS, respectively. Estimates from other PS adjustment approaches showed similar patterns., Conclusions: In a comparative effectiveness study of CAS vs. CEA with strong confounding by indication, ada-PS performed better than IS-PS in general, but both claims and registry data were needed to adequately control for bias., Competing Interests: HK and HM are affiliated with the department of Healthcare Quality Assessment, University of Tokyo, which is a social collaboration department supported by the National Clinical Database, Johnson & Johnson KK, and Nipro Corporation. HK has received lecture fees from Chugai Pharmaceutical Co., Ltd., Johnson & Johnson KK, and consultancy fees from Mitsubishi Tanabe Pharm and EP Croit Co., Ltd. JJJ is a full-time employee of Regeneron Pharmaceuticals. This study was conducted prior to her employment at the company. SS has served as a member of the US FDA advisory committee and as a consultant for Pfizer Inc., Medtronic, and Merck. SS has also received research funding from the National Institutes of Health, the Cystic Fibrosis Foundation, Pfizer Inc., and Bristol-Myers Squibb. All other authors have no conflicts to declare. The above do not alter our adherence to Plos One policies on sharing data and materials.

This paper considers hiding messages in overt transmissions with a full-duplex receiver, which emits artificial noise to secure its transmission connection while a transmitter opportunistically sends a covert message to a covert user. The warden's uncertainties in decoding the overt message and artificial-noise-received power are exploited to hide messages. Then, the covert throughput accompanied with the warden's average detection error probability are determined. The results show that increasing the transmit power of artificial noise or improving secure connection at the overt user will improve the covert performance. The results also show that the covert performance is improved when the self-interference cancellation is improved at the full-duplex receiver or when the warden is located close to the full-duplex receiver, indicating the positive impact of the overt performance on the covert performance.

For successful long-term deployment and operation of kesterites Cu 2 ZnSn(S x Se 1- x ) 4 (CZTSSe) as light-absorber materials for photovoltaics, device stability and recovery in kesterite solar cells are investigated. A low-temperature heat treatment is applied to overcome the poor charge extraction that developed in the natural aging process. It is suggested that defect states at aged CZTSSe/CdS heterojunctions were reduced, while apparent doping density in the CZTSSe absorber increased due to Cd/Zn interdiffusion at the heterojunction during the annealing process. In situ annealing experiments in a transmission electron microscope were used to investigate the elemental diffusion at the CZTSSe/CdS heterojunction. This study reveals the critical role of heat treatment to enhance the absorber/Mo back contact, improve the quality of the absorber/buffer heterojunction, and recover the device performance in aged kesterite thin-film solar cells., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The paper proposes a joint semi-blind algorithm for simultaneously cancelling the self-interference component and estimating the propagation channel in 5G Quasi-Cyclic Low-Density Parity-Check (QC-LDPC)-encoded short-packet Full-Duplex (FD) transmissions. To avoid the effect of channel estimation processes when using short-packet transmissions, this semi-blind algorithm was developed by taking into account only a small number (four at least) pilot symbols, which was integrated with the intended information sequence and used for the feedback loop of the estimation of the channels. The results showed that this semi-blind algorithm not only achieved nearly optimal performance, but also significantly reduced the processing time and computational complexity. This semi-blind algorithm can also improve the performances of the Mean-Squared Error (MSE) and Bit Error Rate (BER). The results of this study highlight the potential efficiency of this joint semi-blind iterative algorithm for 5G and Beyond and/or practical IoT transmission scenarios.

Background: Surgical patients with limited digital literacy may experience reduced telemedicine access. We investigated racial/ethnic and socioeconomic disparities in telemedicine compared with in-person surgical consultation during the coronavirus disease 2019 (COVID-19) pandemic., Study Design: Retrospective analysis of new visits within the Division of General & Gastrointestinal Surgery at an academic medical center occurring between March 24 through June 23, 2020 (Phase I, Massachusetts Public Health Emergency) and June 24 through December 31, 2020 (Phase II, relaxation of restrictions on healthcare operations) was performed. Visit modality (telemedicine/phone vs in-person) and demographic data were extracted. Bivariate analysis and multivariable logistic regression were performed to evaluate associations between patient characteristics and visit modality., Results: During Phase I, 347 in-person and 638 virtual visits were completed. Multivariable modeling demonstrated no significant differences in virtual compared with in-person visit use across racial/ethnic or insurance groups. Among patients using virtual visits, Latinx patients were less likely to have video compared with audio-only visits than White patients (OR, 0.46; 95% CI 0.22-0.96). Black race and insurance type were not significant predictors of video use. During Phase II, 2,922 in-person and 1,001 virtual visits were completed. Multivariable modeling demonstrated that Black patients (OR, 1.52; 95% CI 1.12-2.06) were more likely to have virtual visits than White patients. No significant differences were observed across insurance types. Among patients using virtual visits, race/ethnicity and insurance type were not significant predictors of video use., Conclusion: Black patients used telemedicine platforms more often than White patients during the second phase of the COVID-19 pandemic. Virtual consultation may help increase access to surgical care among traditionally under-resourced populations., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: In response to problems with the current postmarket surveillance of medical devices, the U.S. Food and Drug Administration mandated device labelers to include a unique device identifier (UDI), composed of a device identifier (DI) and production identifier. Including the DI in insurance claims could be a potent method to monitor implanted devices, yet implementation has lagged because of questions of benefit and operational concerns., Methods: To illustrate the potential benefit of including DIs in claims, rates of 90-day adverse events after implantation using an electronic health record (EHR) were compared with the EHR plus claims, which capture utilization outside that EHR's health system. To explore operations, we planned a pilot project to transmit the DI of implanted devices from the point of care to the claim at two provider/payer pairs., Results: By querying claims plus EHR, estimated rates of patients with potential adverse events were as much as 3.75 times higher. For our pilot, our multistakeholder team identified and resolved the following five challenges: (1) capturing the DI at the point of care; (2) selecting a location for the DI on the claim form; (3) transmitting the DI to the claim form; (4) analyzing the claim forms received by the payer; and (5) verifying the quality of the transmitted information., Conclusions: Including DIs on claims could allow more complete data capture of adverse events for implanted devices than the EHR data. We overcame challenges in transmitting the DI to the claim with attention to planning and multistakeholder involvement., (Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.)

Conductive filaments (CFs) play a critical role in the mechanism of resistive random-access memory (ReRAM) devices. However, in situ detection and visualization of the precise location of CFs are still key challenges. We demonstrate for the first time the use of a π-conjugated molecule which can transform between its twisted and planar states upon localized Joule heating generated within filament regions, thus reflecting the locations of the underlying CFs. Customized patterns of CFs were induced and observed by the π-conjugated molecule layer, which confirmed the hypothesis. Additionally, statistical studies on filaments distribution were conducted to study the effect of device sizes and bottom electrode heights, which serves to enhance the understanding of switching behavior and their variability at device level. Therefore, this approach has great potential in aiding the development of ReRAM technology.

Background: Shared decision making and patient-centred communication have become part of pre-procedural decisions and perioperative care across medical specialties. However, gaps exist in patient communication about the implanted device received and the benefits in sharing information about their procedure and device., Objective: To understand the patients' knowledge of identifying information for their implanted devices and perspectives on sharing their implanted device information., Methods: Four focus groups were conducted with patients who had received a cardiac or vascular implanted device from one of the study sites within the previous 6 months. Data were transcribed and thematically analysed., Results: Five themes emerged: lack of awareness of identifying information on implanted devices; value of information on implanted devices; varying trust with sharing device information; perceived risk with sharing device information; and lack of consensus on a systematic process for tracking implanted devices., Discussion: Patients desire post-procedural information on their implanted device and a designated plan for longitudinal follow-up, but lack trust and perceive risk with broadly sharing their implanted device information., Conclusion: After receiving an implanted device, post-procedural patient communication needs to be expanded to include identifying information on the device including the unique device identifier, how long-term tracking will be supported and the process for notification in case of a problem with the device. This communication should also include education on how sharing device information supports patients' long-term health care, post-market safety surveillance and research., Patient or Public Contribution: The research team included members who were also patients with implanted devices., (© 2021 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

This paper describes a rapid bottom-up approach to selectively functionalize gold nanoparticles (AuNPs) on an indium tin oxide (ITO) substrate using the plasmon confinement effect. The plasmonic substrates based on a AuNP-free surfactant were fabricated by electrochemical deposition. Using this bottom-up technique, many sub-30 nm spatial gaps between the deposited AuNPs were randomly generated on the ITO substrate, which is difficult to obtain with a top-down approach (i.e., E-beam lithography) due to its fabrication limits. The 4-Aminodiphenyl (ADP) molecules were grafted directly onto the AuNPs through a plasmon-induced reduction of the 4-Aminodiphenyl diazonium salts (ADPD). The ADP organic layer preferentially grew in the narrow gaps between the many adjacent AuNPs to create interconnected AuNPs. This novel strategy opens up an efficient technique for the localized surface modification at the nanoscale over a macroscopic area, which is anticipated to be an advanced nanofabrication technique.

Objective: We review the existing research on environmentally sustainable surgical practices to enable SAO to advocate for improved environmental sustainability in operating rooms across the country., Summary of Background Data: Climate change refers to the impact of greenhouse gases emitted as a byproduct of human activities, trapped within our atmosphere and resulting in hotter and more variable climate patterns.1 As of 2013, the US healthcare industry was responsible for 9.8% of the country's emissions2; if it were itself a nation, US healthcare would rank 13th globally in emissions.3 As one of the most energy-intensive and wasteful areas of the hospital, ORs drive this trend. ORs are 3 to 6 times more energy intensive than clinical wards.4 Further, ORs and labor/delivery suites produce 50%-70% of waste across the hospital.5,6 Due to the adverse health impacts of climate change, the Lancet Climate Change Commission (2009) declared climate change "the biggest global health threat of the 21st century" and predicted it would exacerbate existing health disparities for minority groups, children and low socioeconomic patients.7., Methods/results: We provide a comprehensive narrative review of published efforts to improve environmental sustainability in the OR while simultaneously achieving cost-savings, and highlight resources for clinicians interested in pursuing this work., Conclusion: Climate change adversely impacts patient health, and disproportionately impacts the most vulnerable patients. SAO contribute to the problem through their resource-intensive work in the OR and are uniquely positioned to lead efforts to improve the environmental sustainability of the OR., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: For implanted devices, an effective postmarket surveillance system does not exist. For medications, the Food and Drug Administration's Sentinel Initiative plays that role, relying mainly on drug codes in insurance claims. Unique device identifiers (UDIs) could play an analogous role for implants, but there is no mandate for providers to include UDIs in claims or for payers to record them. Objections have been raised to incorporating UDIs into claims based on a potential burden on providers., Methods: To assess this purported barrier, we modified information systems at 2 provider-payer dyads to allow for the transmission of UDI data from provider to payer. In addition, to illustrate the potential benefit of including device data in claims, we used our data to compare rates of 90-day adverse events after implantation using the electronic health record (EHR) alone with the EHR plus claims., Results: The software system modifications were modest and performed as designed. Moreover, the level of difficulty of their development and implementation was comparable to that associated with a typical new release of an existing system. In addition, our data demonstrated the ability of claims-based data plus EHR data to reveal a larger percentage of postprocedure adverse events than data from EHRs alone., Conclusions: Modifying information systems to allow for the transmission of UDI data from providers to payers should not impose a substantial burden on either. Implementation of a postmarket surveillance system based on such data in claims will require, however, the development of a system analogous to Sentinel., Competing Interests: The other authors disclose no conflict of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Arterial thoracic outlet syndrome is rare and may be associated with a bony anomaly. Patient presentation can range from mild arm discoloration and claudication to severe limb-threatening ischemia. For patients with subclavian artery dilation without secondary complications, thoracic outlet decompression and arterial surveillance is sufficient. Patients with subclavian artery aneurysms or distal embolization require decompression with reconstruction or thromboembolectomy and distal bypass respectively., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare no conflict of interest.

Background: Preoperative magnetic resonance imaging (MRI) utilization in breast cancer treatment has increased significantly over the past 2 decades, but its use continues to have interprovider variability and disputed clinical indications., Objective: The aim of this study was to evaluate non-clinical factors associated with preoperative breast MRI utilization., Methods: This study utilized TRICARE claims data from 2006 to 2015. TRICARE provides health benefits for active duty service members, retirees, and their dependents at both military (direct care with salaried physicians) and civilian (purchased care under fee-for-service structure) facilities. We studied patients aged 25-64 years with a breast cancer diagnosis who had undergone mammogram/ultrasound (MMG/US) alone or with subsequent breast MRI prior to surgery. Facility characteristics included urban-rural location according to the National Center for Health Statistics classification. Adjusted multivariable logistic regression tests were used to identify independent factors associated with preoperative breast MRI utilization., Results: Of the 25,392 identified patients, 64.7% (n = 16,428) received preoperative MMG/US alone, while 35.3% (n = 8964) underwent additional MRI. Younger age, Charlson Comorbidity Index score ≥ 2, active duty or retired beneficiary category, officer rank (surrogate for socioeconomic status), Air Force service branch, metropolitan location, and purchased care were associated with an increased likelihood of preoperative MRI utilization. Non-metropolitan location and Navy service branch were associated with decreased MRI use., Conclusion: After controlling for expected clinical risk factors, patients were more likely to receive additional MRI when treated at metropolitan facilities or through the fee-for-service system. Both associations may point toward non-clinical incentives to perform MRI in the treatment of breast cancer.

Soft robotics focuses on mimicking natural systems to produce dexterous motion. Dielectric elastomer actuators (DEAs) are an attractive option due to their large strains, high efficiencies, lightweight design, and integrability, but require high electric fields. Conventional approaches to improve DEA performance by incorporating solid fillers in the polymer matrices can increase the dielectric constant but to the detriment of mechanical properties. In the present work, we draw inspiration from soft and deformable human skin, enabled by its unique structure, which consists of a fluid-filled membrane, to create self-enclosed liquid filler (SELF)-polymer composites by mixing an ionic liquid into the elastomeric matrix. Unlike hydrogels and ionogels, the SELF-polymer composites are made from immiscible liquid fillers, selected based on interfacial interaction with the elastomer matrix, and exist as dispersed globular phases. This combination of structure and filler selection unlocks synergetic improvements in electromechanical properties-doubling of dielectric constant, 100 times decrease in Young's modulus, and ∼5 times increase in stretchability. These composites show superior thermal stability to volatile losses, combined with excellent transparency. These ultrasoft high- k composites enable a significant improvement in the actuation performance of DEAs-longitudinal strain (5 times) and areal strain (8 times)-at low applied nominal electric fields (4 V/μm). They also enable high-sensitivity capacitive pressure sensors without the need of miniaturization and microstructuring. This class of self-enclosed ionic liquid polymer composites could impact the areas of soft robotics, shape morphing, flexible electronics, and optoelectronics.

Growing interest in soft robotics, stretchable electronics, and electronic skins has created demand for soft, compliant, and stretchable electrodes and interconnects. Here, dielectrophoresis (DEP) is used to assemble, align, and sinter eutectic gallium indium (EGaIn) microdroplets in uncured poly(dimethylsiloxane) (PDMS) to form electrically conducting microwires. There are several noteworthy aspects of this approach. 1) Generally, EGaIn droplets in silicone at loadings approaching 90 wt% remain insulating and form a conductive network only when subjected to sintering. Here, DEP facilitates assembly of EGaIn droplets into conductive microwires at loadings as low as 10 wt%. 2) DEP is done in silicone for the first time, enabling the microwires to be cured in a stretchable matrix. 3) Liquid EGaIn droplets sinter during DEP to form a stretchable metallic microwire that retains its shape after curing the silicone. 4) Use of liquid metal eliminates the issue of compliance mismatch observed in soft polymers with solid fillers. 5) The silicone-EGaIn "ink" can be assembled by DEP within the crevices of severely damaged wires to create stretchable interconnects that heal the damage mechanically and electrically. The DEP process of this unique set of materials is characterized and the interesting attributes enabled by such liquid microwires are demonstrated., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Epidural analgesia (EA) is frequently used as an adjuvant to general anesthesia (GA) for improved postoperative analgesia and reduced rates of cardiac, pulmonary, and renal complications. However, only a few studies have examined EA-GA specifically during open abdominal aortic aneurysm (AAA) repair. The effects of EA-GA specifically during open AAA repair regarding postoperative outcomes are unknown. This study was performed to evaluate postoperative outcomes in patients undergoing open AAA repair with EA-GA versus GA alone., Methods: We performed a retrospective analysis for patients undergoing surgery between January 1, 2014 and December 31, 2016 using the National Surgical Quality Improvement Program (NSQIP) database. Propensity score matching was used to establish cohorts for analysis. Multivariable logistic regression was performed to determine significant perioperative outcomes for each anesthesia type. A total of 2,171 patients underwent open AAA repair in our date range; we excluded emergent and ruptured AAA. A total of 2,145 patients were included in our analysis, of whom 653 patients received EA-GA and 1,492 patients received GA only., Results: Major postoperative outcomes included mortality, pulmonary cardiac and renal complications, infections, thrombosis, and blood transfusion requirement (including Cell-Saver usage). Additional overall outcomes included hospital length of stay, return to the operating room, and readmission. Patients in EA + GA and GA alone groups were comparable regarding demographics, functional status, and comorbidities. Decreased odds of readmission was observed in EA + GA compared with GA (0.49, 95% CI [0.28-0.86]; P = 0.014); and increased odds of receiving a blood transfusion was observed in those who underwent EA + GA (1.63, 95% CI [1.23-2.14]; P = 0.001). No difference was observed between patients who had an AAA repair with EA + GA versus GA alone with regard to mortality, return to operating room, major pulmonary, cardiac, renal, or infectious complications., Conclusions: EA + GA was not associated with decreased mortality or decreased rates of major postoperative pulmonary, cardiac, or renal complications. EA + GA was associated with increased transfusion requirements and decreased rates of hospital readmission., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Fragmentation of outpatient care is a substantial barrier to creation and maintenance of hemodialysis access. To improve patient accessibility, satisfaction, and multidisciplinary provider communication, we created a monthly Saturday multidisciplinary vascular surgery and interventional nephrology access clinic at a tertiary care hospital in a major urban area for the complicated hemodialysis patient population. The study included patients presenting for new access creation as well as those who had previously undergone access surgery. Staffing included two to three interventional nephrologists, two to three vascular surgeons, one medical assistant, one research assistant, and one practice assistant. Patient satisfaction and perception of the clinic was measured using surveys during six of the monthly Saturday hemodialysis clinics. A total of 675 patient encounters were completed (18.2 average/clinic ±6.3 standard deviation) from August 2016 to August 2019. All patients were seen by both disciplines. The average no-show rate was 19.9% throughout the study period. Patient satisfaction in all measures was consistently high with the Saturday clinic. Providers were also assayed, and they generally valued the real-time, multidisciplinary care plan generation, and its subsequent efficient execution. Saturday multidisciplinary hemodialysis access clinics offer high provider and patient satisfaction and streamlined patient care. However, no-show rates remain relatively high for this challenging patient population.

Objective: Severe aortoiliac occlusive disease is a relative contraindication for endovascular aneurysm repair, owing to an association with high stent graft-related complication and reintervention rates in this population. Open AAA repair requiring aortofemoral bypass (AFB), however, may represent a unique population with differing outcomes from standard open repair. We sought to compare the demographic and procedural characteristics, as well as outcomes of patients undergoing standard intra-abdominal repairs (STD) versus those requiring AFB., Methods: Using a prospectively maintained database, we retrospectively identified patients who underwent open AAA repair from 1994 to 2017. A total of 1087 consecutive cases were performed consisting of 981 STD (681 tube graft, 300 aortoiliac) and 106 AFB cases. Demographics, procedural data, postoperative complications, and long-term survival were analyzed., Results: The AFB cohort had more women (39.0 vs 22.8%; P = .001) and higher rates of hypertension (81.1 vs 69.8%; P = .015), chronic obstructive pulmonary disease (28.3 vs 17.4%; P = .006), and smoking (50.9 vs 36%; P = .002). The AFB group had smaller mean aortic (5.22 vs 5.77 cm; P = .001) and graft (17.08 vs 18.2 mm; P = .001) diameters. Proximal clamp position and blood loss were equivalent, although total anesthesia time was longer (295 vs 234 minutes; P = .001) in the AFB cohort. Overall 30-day postoperative morbidity (38.7 vs 24.8%; P = .002) was higher in the AFB group. Specifically, postoperative renal insufficiency (8.2 vs 3.4%; P = .032), wound infection (5.7 vs 1.2%; P = .005), and hematoma/seroma (5.7 vs 1.2%; P = .003) were more likely. Hospital length of stay was longer for AFB (11.9 vs 9.9 days; P = .007). The 30-day mortality (0.9% AFB vs 1.8% STD; P = .50) and major morbidity (17 vs 11.5%; P = .10) did not differ. Reintervention rate within 30 days of the initial surgery (12.3 vs 4.6; P = .001) and overall (33 vs 18.9%; P = .001) was higher in the AFB group. Long-term survival was lower in the AFB group (5-year survival: 63.1% AFB vs 71.9% STD; hazard ratio 0.76, log-rank P = .047). Multivariate regression analysis identified age, comorbid conditions, and aneurysm characteristics-rather than repair type-as independent predictors of 30-day reintervention and mortality at 5 years., Conclusions: Patients requiring AFB for AAA owing to associated iliac occlusive disease have more preoperative comorbidities, postoperative complications, a longer length of stay, reintervention rates and shorter 5-year survival. Patient and aneurysm characteristics rather than surgical repair type appear to be responsible for these differences. Nevertheless, 30-day mortality and major morbidity were comparable, making AFB an attractive alternative to endovascular aneurysm repair in patients with advanced iliac occlusive disease., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Vascular surgeons are frequently called on to provide emergency assistance to surgical colleagues. Whereas previous studies have included elective preoperative vascular consultations, we sought to characterize the breadth of assistance provided during unplanned intraoperative consultations at a single tertiary academic center., Methods: We queried our institutional billing department during a 15-year period and reviewed the records (January 1, 2002-December 31, 2016) and identified unanticipated unplanned vascular surgery intraoperative consultations from all surgical services. Patients' demographics and comorbidities were recorded along with the consulting services, type of index operation, reasons for vascular consultation, regions of anatomic interventions, type of vascular interventions performed, and outcomes achieved., Results: There were 419 emergency intraoperative consultations identified. Patients were 51% male, with an average age of 57 years and body mass index of 28.3 kg/m 2 . The most frequently consulting subspecialties included surgical oncology (n = 139 [33.2%]), cardiac surgery (n = 82 [19.6%]), and orthopedics (n = 44 [10.5%]). Index cases were elective/nonurgent (n = 324 [77.3%]), urgent (n = 27 [6.4%]), and emergent (n = 68 [16.2%]), with a majority involving tumor resection (n = 240 [57.3%]). The primary reasons for vascular consultation were revascularization (n = 213 [50.8%]), control of bleeding (n = 132 [31.5%]), assistance with dissection or exposure (n = 46 [11%]), embolic protection (n = 24 [5.7%]), and other (n = 4 [1.1%]). The primary blood vessel and anatomic field of intervention were categorized. Most cases (n = 264 [63%]) included preservation of blood flow, including primary arterial repair (n = 181 [43.2%]), patch angioplasty (n = 83 [19.8%]), bypass (n = 63 [15%]), and thrombectomy (n = 38 [9.1%]). Postoperative mean length of stay was 15 days, with 30-day and 1-year mortality of 7.2% and 26.5%., Conclusions: Vascular surgeons are called on to provide unplanned open surgical consultations for a wide variety of specialties over wide-ranging anatomic regions, employing a variety of skills and techniques. This study testifies to the essential services supplied to hospitals and our surgical colleagues along with the broad skills and training necessary for modern vascular surgeons., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Index length of stay (LOS) and readmissions are viewed as important quality measures. However, these metrics represent competing demands as an inordinate reduction in LOS may lead to unplanned readmissions. We sought to assess the optimal LOS associated with the lowest 90-d readmission rate following discharge after common surgical procedures., Materials and Methods: This was a retrospective study relying on Tricare claims. We identified all eligible adult patients (18-64 y) receiving a series of common surgical procedures between 2006 and 2014. We used a generalized additive model with spline regression to determine the optimal LOS associated with the lowest 90-d risk of readmission., Results: Ninety-day readmission rates varied from 6.03% to 34.69%. Most procedures exhibited a logit linear relationship, with the lowest risk of readmission evident on postoperative day-1 and increasing thereafter. Among the more invasive procedures (e.g., esophagectomy and radical cystectomy), a U-shaped relationship was realized, indicating that expedited discharge would increase the potential for readmission as would any extended hospital LOS. For these procedures, the ideal index LOS appeared to be 6-7 d for radical cystectomy and 12-13 d for esophagectomy., Conclusions: Our results support the practice of discharging patients as soon as clinically feasible after hip and knee arthroplasty, lumbar spine surgery, hernia repair, appendectomy, nephrectomy, and colectomy. Among esophagectomy or radical cystectomy, there is a well-defined optimal index admission period and discharge outside this window appears to be detrimental. Our results suggest that invasive procedures appear to possess a unique "signature" when it comes to optimal LOS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Racial disparities in colorectal cancer (CRC) screening are frequently attributed to variations in insurance status. The objective of this study was to ascertain whether universal insurance would lead to more equitable utilization of CRC screening for black patients in comparison with white patients., Methods: Claims data from TRICARE (insurance coverage for active, reserve, and retired members of the US Armed Services and their dependents) for 2007-2010 were queried for adults aged 50 years in 2007, and they were followed forward in time for 4 years (ages, 50-53 years) to identify their first lower endoscopy and/or fecal occult blood test (FOBT). Variations in CRC screening were compared with descriptive statistics and multivariate logistic regression., Results: Among the 24,944 patients studied, 69.2% were white, 20.3% were black, 4.9% were Asian, and 5.6% were other. Overall, 54.0% received any screening: 83.7% received endoscopy, and 16.3% received FOBT alone. Compared with whites, black patients had higher screening rates (56.5%) and had 20% higher risk-adjusted odds of being screened (95% confidence interval [CI], 1.11-1.29). Asian patients had a likelihood of screening similar to that of white patients (odds ratio [OR], 1.06; 95% CI, 0.92-1.23). Females (OR, 1.20; 95% CI, 1.10-1.33), active-duty personnel (OR, 1.15; 95% CI, 1.06-1.25), and officers (OR, 1.28; 95% CI, 1.18-1.37) were also more likely to be screened., Conclusion: Within an equal-access, universal health care system, black patients had higher rates of CRC screening in comparison with prior reports and even in comparison with white patients within the population. These findings highlight the need to understand and develop meaningful approaches for promoting more equitable access to preventative care. Moreover, equal-access, universal health insurance for both the military and civilian populations can be presumed to improve access for underserved minorities., (© 2018 American Cancer Society.)

Background: The natural history of postinjury among elderly trauma patients has not been well described. We hypothesized that elderly trauma patients would have lower admission hemoglobin (Hb) levels, higher transfusion rates, and worse outcomes than young trauma patients., Methods: We performed a propensity-matched retrospective cohort analysis comparing elderly (age ≥65 y) to young (age 18-64) trauma patients matched by sex, mechanism of injury, Injury Severity Score, base deficit, comorbidities, operative blood loss, and phlebotomy blood loss (n = 41/group). Outcomes included Hb trends, packed red blood cell (PRBC) transfusion, length of stay, and mortality., Results: Elderly patients had lower admission Hb (11.3 versus 10.2 g/dL, P = 0.012), received more PRBC transfusions within 24 h (3.6 versus 1.8 units, P = 0.046), and during admission (6.9 versus 4.3 units, P = 0.008). Despite receiving more PRBC transfusions and having similar operative and phlebotomy blood loss, elderly subjects had lower discharge Hb (9.0 versus 9.7 g/dL, P = 0.013). Elderly subjects had fewer ICU-free days (2.0 versus 6.0 d, P < 0.001) and higher in-hospital mortality (15% versus 0%, P = 0.026)., Conclusions: Elderly trauma patients had lower admission Hb, received more transfusions, and had persistently lower Hb on discharge when controlling for injury severity, comorbid conditions, and blood loss. Aging may have a negative impact on postinjury anemia., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The transcription factor Nrf2 is a master regulator of antioxidant and cytoprotective genes, binding to antioxidant response elements (AREs) in their promoter regions. Due to the therapeutic role of the Nrf2/ARE system in oxidative homeostasis, its activation has been investigated in many pre-clinical and clinical trials for common chronic diseases. One of the most promising Nrf2 activators is sulforaphane, the subject of over 50 clinical trials. In this work, we examine the effect of reactive oxygen species (ROS) on sulforaphane's Nrf2/ARE activation in the non-tumorigenic keratinocyte cell line HaCaT, with the non-arylating oxidizable phenol, 2,5-di-tert-butylhydroquinone (dtBHQ), as the source of ROS. We find that, in combination with 2.5 µM sulforaphane, dtBHQ markedly enhances ARE-regulated gene expression, including expression of the cytoprotective proteins aldo-keto reductase family 1 member C1 (AKR1C1) and heme oxygenase-1 (HO-1). Additionally, sulforaphane's therapeutic window is widened by 12.5 µM dtBHQ. Our data suggest that H 2 O 2 generated by dtBHQ oxidation is responsible for these effects, as shown by inclusion of catalase and by co-treatment with sulforaphane and H 2 O 2 . While sulforaphane treatment causes Nrf2 protein to accumulate as expected, interestingly, dtBHQ and H 2 O 2 appear to act on targets downstream of Nrf2 protein accumulation to enhance sulforaphane's ARE-regulated gene expression. Inclusion of dtBHQ or H 2 O 2 with sulforaphane does not increase Nrf2 protein levels, and catalase has little effect on Nrf2 protein levels in the presence of sulforaphane and dtBHQ. Surprisingly, dtBHQ suppresses Nrf2 protein synthesis. Inclusion of a superoxide dismutase mimetic with sulforaphane and dtBHQ partly rescues Nrf2 suppression and significantly further increases sulforaphane's efficacy for ARE-reporter expression. Thus, there is a "Dr. Jekyll and Mr. Hyde" effect of ROS: ROS enhance sulforaphane's ARE-regulated gene expression even as they also inhibit Nrf2 protein synthesis. This unexpected finding reveals the degree to which targets in the ARE pathway downstream of Nrf2 protein accumulation contribute to gene expression. The results presented here provide a model system for significant enhancement of sulforaphane's potency with small molecule co-treatment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Despite their extensive industrial usage, glass-forming liquids are not fully understood, and methods to investigate their dynamical heterogeneity are sought after. Here we show how the appearance of a second component in the visible absorption spectrum of a photosynthetic pigment upon cooling can be used to probe the glass transition of a dimethylsulfoxide-water mixture. The changes in the relative ratio of the two components with respect to temperature follow a sigmoid curve, and we show that the second component arises due to protonation of the pigment at low temperatures. Furthermore, from visible transient absorption spectra we show that, unlike the first component, the dynamics of the second component slows down significantly at lower temperatures, suggesting that there are two distinct environments with fast and slow fluctuations. Our results therefore enable a new method to characterize the dynamical heterogeneity of glass-forming liquids.

Critical limb ischemia (CLI) is a frequent and major vascular problem and can lead to amputation and death despite surgical revascularization. Women have been shown to have 3 to 4 per cent lower revascularization rates for CLI compared with men as well as inferior outcomes. We hypothesize that this difference is a result of women being more likely admitted to low-volume hospitals, which in turn perform fewer revascularizations. Prospective cohort study. Data from the Nationwide Inpatient Sample 2007 to 2010 were used to identify admissions with primary International Classification of Diseases-9 codes for CLI (International Classification of Diseases-9 codes: 440.22, 440.23, 440.24, 707.1, 707.10-707.15, or 707.19). Hospitals were grouped in quintiles by annual revascularization procedures. Bivariate analyses were performed and multivariable logistic regression was used to analyze the odds of revascularization, amputation, and mortality while controlling for patient and hospital-level factors. Of 113,631 admissions, 54,370 (47.8%) were women, who were more likely admitted to low-volume hospitals (very low: 49.6% vs very high: 47.1%; P < 0.001). Revascularization rates were lower in women (31.6% vs 35.1%, P < 0.001) across all volume quintiles, whereas the difference was greatest in the use of open surgical revascularization (12.5% vs 16.0%, P < 0.001). In multivariable analysis, female gender [odds ratio (OR) 0.87, 95% confidence interval (CI) 0.83-0.92, P < 0.001] and very-low hospital volume (OR 0.21, 95% CI 0.17-0.26, P < 0.001) were both significantly associated with lower rates of revascularization. Women had lower odds of major amputation compared with men (OR 0.75, 95% CI 0.69-0.82, P < 0.001), whereas treatment in a very high-volume hospital was associated with increased odds for amputation (OR 1.37, 95% CI 1.09-1.73, P = 0.008). Neither gender nor hospital volume were independently associated with in-hospital mortality in the multivariable regression model. Women are more likely to be admitted to low-volume hospitals for treatment of CLI. Because of this, they are less likely to undergo revascularization, although they also had lower rates of major amputation.

Objective: The clinical impact of peripheral arterial disease (PAD) is well characterized and is associated with significant morbidity and mortality. Health care-related expenditures among individuals with PAD, particularly for patients, are not well described., Methods: Health care-related expenditure data from the 2011 to 2014 Agency for Healthcare Research and Quality Medical Expenditure Panel Surveys were analyzed for individuals with a diagnosis of PAD compared with U.S. adults 40 years of age and older. Weighted average annual expenditures were estimated using a multivariable generalized linear model. Subanalyses were also performed for out-of-pocket (OOP) expenditures by insurance type., Results: Adjusted for age, gender, and race, individuals with a diagnosis of PAD (weighted n = 640,098) had significantly higher average annual health care-related expenditures compared with the U.S. adult population as a whole (weighted n = 148,387,362). Average annual expenditures per individual for patients with PAD were $11,553 (95% confidence interval [CI], $8137-$14,968) compared with only $4219 (95% CI, $4064-$4375; P < .001) for those without. Expenditures were driven by increased prescription medication expenditures as well as by expenditures for inpatient care, outpatient hospital-based care, and outpatient office-based care. Individuals with PAD had significantly higher OOP prescription medication expenditures ($386 [95% CI, $258-$515] vs $192 [95% CI, $183-$202]; P = .003), which varied by insurance type, ranging from $179 (95% CI, $70-$288) for those with Medicare to $1196 (95% CI, $106-$2244) for those without insurance, although this difference did not reach significance., Conclusions: Individuals with a diagnosis of PAD have higher health care-related expenditures and OOP expenses compared with other US adults. These expenditures compound lost wages, care by family members, and lost opportunity costs, increasing the burden carried by patients with PAD., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Decision-making related to the care of patients with an abdominal aortic aneurysm (AAA) is complex. Aneurysms present with varying risks of rupture, and patient-specific factors influence anticipated life expectancy, operative risk, and need to intervene. Careful attention to the choice of operative strategy along with optimal treatment of medical comorbidities is critical to achieving excellent outcomes. Moreover, appropriate postoperative surveillance is necessary to minimize subsequent aneurysm-related death or morbidity., Methods: The committee made specific practice recommendations using the Grading of Recommendations Assessment, Development, and Evaluation system. Three systematic reviews were conducted to support this guideline. Two focused on evaluating the best modalities and optimal frequency for surveillance after endovascular aneurysm repair (EVAR). A third focused on identifying the best available evidence on the diagnosis and management of AAA. Specific areas of focus included (1) general approach to the patient, (2) treatment of the patient with an AAA, (3) anesthetic considerations and perioperative management, (4) postoperative and long-term management, and (5) cost and economic considerations., Results: Along with providing guidance regarding the management of patients throughout the continuum of care, we have revised a number of prior recommendations and addressed a number of new areas of significance. New guidelines are provided for the surveillance of patients with an AAA, including recommended surveillance imaging at 12-month intervals for patients with an AAA of 4.0 to 4.9 cm in diameter. We recommend endovascular repair as the preferred method of treatment for ruptured aneurysms. Incorporating knowledge gained through the Vascular Quality Initiative and other regional quality collaboratives, we suggest that the Vascular Quality Initiative mortality risk score be used for mutual decision-making with patients considering aneurysm repair. We also suggest that elective EVAR be limited to hospitals with a documented mortality and conversion rate to open surgical repair of 2% or less and that perform at least 10 EVAR cases each year. We also suggest that elective open aneurysm repair be limited to hospitals with a documented mortality of 5% or less and that perform at least 10 open aortic operations of any type each year. To encourage the development of effective systems of care that would lead to improved outcomes for those patients undergoing emergent repair, we suggest a door-to-intervention time of <90 minutes, based on a framework of 30-30-30 minutes, for the management of the patient with a ruptured aneurysm. We recommend treatment of type I and III endoleaks as well as of type II endoleaks with aneurysm expansion but recommend continued surveillance of type II endoleaks not associated with aneurysm expansion. Whereas antibiotic prophylaxis is recommended for patients with an aortic prosthesis before any dental procedure involving the manipulation of the gingival or periapical region of teeth or perforation of the oral mucosa, antibiotic prophylaxis is not recommended before respiratory tract procedures, gastrointestinal or genitourinary procedures, and dermatologic or musculoskeletal procedures unless the potential for infection exists or the patient is immunocompromised. Increased utilization of color duplex ultrasound is suggested for postoperative surveillance after EVAR in the absence of endoleak or aneurysm expansion., Conclusions: Important new recommendations are provided for the care of patients with an AAA, including suggestions to improve mutual decision-making between the treating physician and the patients and their families as well as a number of new strategies to enhance perioperative outcomes for patients undergoing elective and emergent repair. Areas of uncertainty are highlighted that would benefit from further investigation in addition to existing limitations in diagnostic tests, pharmacologic agents, intraoperative tools, and devices., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Importance: The overprescription of pain medications has been implicated as a driver of the burgeoning opioid epidemic; however, few guidelines exist regarding the appropriateness of opioid pain medication prescriptions after surgery., Objectives: To describe patterns of opioid pain medication prescriptions after common surgical procedures and determine the appropriateness of the prescription as indicated by the rate of refills., Design, Setting, and Participants: The Department of Defense Military Health System Data Repository was used to identify opioid-naive individuals 18 to 64 years of age who had undergone 1 of 8 common surgical procedures between January 1, 2005, and September 30, 2014. The adjusted risk of refilling an opioid prescription based on the number of days of initial prescription was modeled using a generalized additive model with spline smoothing., Exposures: Length of initial prescription for opioid pain medication., Main Outcomes and Measures: Need for an additional subsequent prescription for opioid pain medication, or a refill., Results: Of the 215 140 individuals (107 588 women and 107 552 men; mean [SD] age, 40.1 [12.8] years) who underwent a procedure within the study time frame and received and filled at least 1 prescription for opioid pain medication within 14 days of their index procedure, 41 107 (19.1%) received at least 1 refill prescription. The median prescription lengths were 4 days (interquartile range [IQR], 3-5 days) for appendectomy and cholecystectomy, 5 days (IQR, 3-6 days) for inguinal hernia repair, 4 days (IQR, 3-5 days) for hysterectomy, 5 days (IQR, 3-6 days) for mastectomy, 5 days (IQR, 4-8 days) for anterior cruciate ligament repair and rotator cuff repair, and 7 days (IQR, 5-10 days) for discectomy. The early nadir in the probability of refill was at an initial prescription of 9 days for general surgery procedures (probability of refill, 10.7%), 13 days for women's health procedures (probability of refill, 16.8%), and 15 days for musculoskeletal procedures (probability of refill, 32.5%)., Conclusions and Relevance: Ideally, opioid prescriptions after surgery should balance adequate pain management against the duration of treatment. In practice, the optimal length of opioid prescriptions lies between the observed median prescription length and the early nadir, or 4 to 9 days for general surgery procedures, 4 to 13 days for women's health procedures, and 6 to 15 days for musculoskeletal procedures.

Background: The relationship between patient expectations and patient-reported outcomes (PROs) in total hip arthroplasty (THA) patients is controversial. The purpose of this study was to examine the impact of preoperative patient expectations on postoperative PROs and patient satisfaction., Methods: This was a prospective multicenter observational cohort study of primary THA patients. Preoperatively, patients completed Hospital for Special Surgery (HSS) Hip Replacement Expectations Survey (expectations), 12 item Short Form Survey (SF-12), University of California, Los Angeles (UCLA) activity score, and Hip Disability and Osteoarthritis Score (HOOS). Postoperatively at 6 months and 1 year, patients completed the Hospital for Special Surgery Hip Replacement Fulfillment of Expectations Survey (fulfillment of expectations), a satisfaction survey, and the same PROs as preoperatively. Stepwise multivariate regression models were created., Results: A total of 207 patients were enrolled. Follow-up rate was 91% at 6 months and 92% at 1 year. Being employed and lower baseline HOOS predicted higher expectations (employment status: B = -7.5, P = .002; HOOS: B = -0.27, P = .002). Higher preoperative expectations predicted greater improvements in UCLA activity, SF-12 physical component score, and HOOS at 6 months (UCLA activity: B = 0.03, P = .001; SF-12 physical component score: B = 0.15, P = .001; HOOS: B = 0.20; P = .008) and UCLA activity at 1 year (B = 0.02, P = .004). Furthermore, higher expectations predicted higher postoperative satisfaction and fulfillment of expectations at 6 months (satisfaction: B = 0.21, P < .001; fulfillment of expectations: B = 0.30, P < .001) and higher fulfillment of expectations at 1 year (B = 0.17, P = .006)., Conclusion: In patients undergoing THA, being employed and worse preoperative hip function predict of higher preoperative expectations of surgery. Higher expectations predict greater improvement in PROs, greater patient satisfaction, and the fulfillment of expectations. These findings can be used to guide patient counseling and shared decision making preoperatively., (Copyright © 2017 Elsevier Inc. All rights reserved.)