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Objective: The coronavirus disease 2019 (COVID-19) pandemic has resulted in a marked increase in hospital usage, medical resource scarcity, and rationing of surgical procedures. This has created the need for strategies to triage surgical patients. We have described our experience using the American College of Surgeons (ACS) COVID-19 guidelines for triage of vascular surgery patients in an academic surgery practice., Methods: We used the ACS guidelines as a framework to direct the triage of vascular surgery patients during the COVID-19 pandemic. We retrospectively analyzed the results of this triage during the first month of surgical restriction at our hospital. Patients undergoing surgery were identified by reviewing the operating room schedule. We reviewed the electronic medical records (EMRs) and assigned an ACS category, condition, and tier class to each completed surgery. Surgeries that were postponed during the same period were identified from a prospectively maintained list. We reviewed the EMRs for all postponed surgeries and assigned an ACS category, condition, and tier class to each surgery. We reviewed the EMRs for all postponed procedures to identify any adverse events related to the treatment delay., Results: We performed 69 surgeries in 52 patients during the study period. All surgeries were performed to treat emergent, urgent, or time-sensitive elective diagnoses. Of the 69 surgeries, 47 (68%) were from tier 3 and 22 (32%) from tier 2b. We did not perform any surgeries from tier 1 or 2a. We postponed surgery for 66 patients during the same period, of which 36 (55%) were from tier 1, 22 (33%) from tier 2a, 5 (8%) from tier 2b, and 3 (5%) could not be assigned a tier class. No tier 3 surgeries were postponed. Of the 66 patients, 3 (4.5%) experienced an adverse event that could be attributed to the treatment delay., Conclusions: The ACS triage guidelines provided an effective method to decrease vascular surgical volumes during the COVID-19 pandemic without an increase in patient morbidity. We believe the clinical utility of the guidelines would be strengthened by incorporating the SURGCON/VASCCON (surgical activity condition/vascular activity condition) threat level alert system., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Importance: The sociopolitical and cultural context of graduate surgical education has changed considerably over the past 2 decades. Although new structures of graduate surgical training programs have been developed in response and the comparative value of formats are continually debated, it remains unclear how different time-based structural paradigms are preparing trainees for independent practice after program completion., Objective: To investigate the factors associated with trainees' and program directors' perception of trainee preparedness for independent surgical practice., Design, Setting, and Participants: This qualitative study used an instrumental case study approach and obtained information through semistructured interviews, which were analyzed using open-and-focused coding. Participants were recent graduates and program directors of vascular surgery training programs in the United States. The 2 training paradigms analyzed were the integrated vascular surgery residency program (0 + 5, with 0 indicating that the general surgery training experiences are fully integrated into the 5 years of overall training and 5 indicating the total number of years of training) and the traditional vascular surgery fellowship program (5 + 2, with 5 indicating the number of years of general surgery training and 2 indicating the number of years of vascular surgery training). All graduates completed their training in 2018. All interviews were conducted between July 1, 2018, and September 30, 2018., Main Outcomes and Measures: A conceptual framework to inform current and ongoing efforts to optimize graduate surgical training programs across specialties., Results: A total of 22 semistructured interviews were completed, involving 7 graduates of 5 + 2 programs, 9 graduates of 0 + 5 programs, and 6 vascular surgery program directors. Of the 22 participants, 15 were men (68%). Participants described 4 interconnected domains that were associated with trainees' perceived preparedness for practice: structural, individual, relational, and organizational. Structural factors included the overall and vascular surgery-specific time spent in training, whereas individual factors included innate technical skills, confidence, maturity, and motivation. Faculty-trainee relationships (or relational factors) were deemed important for building trust and granting of autonomy. Organizational factors included features of the local organization, including patient population, case volume, and case mix., Conclusions and Relevance: Findings suggest that restructuring training paradigms alone is insufficient to address the issue of trainees' perceived preparedness for practice. A framework was created from the results for evaluating and improving residency and fellowship programs as well as for developing graduate surgical training paradigms that incorporate all 4 domains associated with preparedness.

Background: Academic institutions have increasingly focused on educating physicians and surgeons in concepts of value-based care, including quality improvement (QI). The extent to which QI curricular competencies are addressed in specialty surgical residency training is unclear., Methods: A survey instrument was developed by content experts and sent to Vascular Surgery and Urology residents electronically. Descriptive statistics and bivariate associations were calculated using StataMP 13.1., Results: Vascular Surgery and Urology residents reported exposure to similar types of QI curriculum. Fewer than half of residents reported achieving targets for graduation (Vascular 31%, Urology 42%) related to QI, and few residents in either group felt very well-prepared to lead a QI initiative (Vascular 13%, Urology 8%)., Conclusion: QI education in surgical specialty training amongst Vascular Surgery and Urology residencies is similar and insufficient. Surgical specialties may benefit from collaborative efforts to improve the quality of QI education., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Abstract: Snyder, NC, Willoughby, CA, and Smith, BK. Comparison of the Polar V800 and the Garmin Forerunner 230 to predict V̇o2max. J Strength Cond Res 35(5): 1403-1409, 2021-The purpose of this study was to compare maximal oxygen consumption (V̇o2max) values (Amax) with predicted V̇o2max values obtained from the Polar V800 (PV800) and the Garmin Forerunner 230 (GF230) to determine whether the accuracy of these estimates differs between sexes. The PV800 predicts V̇o2max based on resting heart rate (HR). The GF230 predicts V̇o2max based on a 10-minute, self-paced outdoor run. Subjects consisted of 22 women and 22 men. After a 10-minute supine rest, predicted V̇o2max (Pmax) values from the PV800 were measured during a 5-minute supine rest. Subjects then completed a treadmill V̇o2max test to determine Amax. Within 48 hours of obtaining Amax, individuals completed a 10-minute, self-paced outdoor run using the GF230 to predict V̇o2max (Gmax). A 2-way (watch vs. sex) analysis of variance was used to determine whether there were differences between predicted V̇o2max and Amax between sexes. A significant interaction between HR monitors and sex was found (p = 0.007). Follow-up analysis showed that in men, Pmax was significantly overestimated compared with Gmax (3.87 ± 1.53 ml·kg-1·min-1, p = 0.013). Bland-Altman plots revealed large random errors that ranged from 6.6 to 16.4 ml·kg-1·min-1 with the PV800 having larger errors than the GF230. The results of this study indicate that the GF230 can provide an accurate estimate of V̇o2max in both sexes. The PV800 can provide an accurate estimate of V̇o2max for women but not men. Estimates of V̇o2max from the both devices should be used with caution because of the large random error associated with them., (Copyright © 2019 National Strength and Conditioning Association.)

Competing Interests: The authors report no conflicts of interest.

Background: Next generation sequencing (NGS) technology has been used for a wide range of epidemiological and surveillance studies. Here, we used amplicon-based NGS to species identify Rickettsia and their arthropod hosts from entomological surveillance., Methods: During 2015-2016, we screened 1825 samples of rodents and ectoparasites collected from rodents and domestic mammals (dog, cat, and cattle) across Thailand for Rickettsia . The citrate synthase gene was amplified to identify Rickettsia to species, while the Cytochrome Oxidase subunit I ( CO I) and subunit II ( CO II) genes were used as target genes for ectoparasite identification. All target gene amplicons were pooled for library preparation and sequenced with Illumina MiSeq platform., Result: The highest percentage of Rickettsia DNA was observed in fleas collected from domestic animals (56%) predominantly dogs. Only a few samples of ticks from domestic animals, rodent fleas, and rodent tissue were positive for Rickettisia DNA. NGS based characterization of Rickettsia by host identified Rickettsia asembonensis as the most common bacteria in positive fleas collected from dogs (83.2%) while " Candidatus Rickettsia senegalensis" was detected in only 16.8% of Rickettsia positive dog fleas. Sequence analysis of CO I and CO II revealed that almost all fleas collected from dogs were Ctenocephalides felis orientis . Other Rickettsia species were detected by NGS including Rickettsia heilongjiangensis from two Haemaphysalis hystricis ticks, and Rickettsia typhi in two rodent tissue samples., Conclusion: This study demonstrates the utility of NGS for high-throughput sequencing in the species characterization/identification of bacteria and ectoparasite for entomological surveillance of rickettsiae. A high percentage of C. f. orientis are positive for R. asembonensis . In addition, our findings indicate there is a risk of tick-borne Spotted Fever Group rickettsiosis, and flea-borne murine typhus transmission in Tak and Phangnga provinces of Thailand.

Reported coronavirus disease 2019 (COVID-19) case counts likely underestimate the true prevalence because mild or asymptomatic cases often go untested. Here, we use a sero-survey to estimate the seroprevalence of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the St. Louis, MO, metropolitan area in a symptom-independent manner. Five hundred three adult and 555 pediatric serum/plasma samples were collected from patients presenting to Barnes-Jewish Hospital or St. Louis Children's Hospital between 14 April 2020 and 12 May 2020. We developed protocols for in-house enzyme-linked immunosorbent assays (ELISAs) using spike and nucleoprotein and used the assays to estimate a seroprevalence rate based on our samples. Overall IgG seropositivity was estimated to be 1.71% (95% credible interval [CI], 0.04% to 3.38%) in pediatric samples and 3.11% (95% CI, 0.92% to 5.32%) in adult samples. Seropositivity was significantly lower in children under 5 years of age than in adults, but rates between adults and children aged 5 or older were similar. Of the 176 samples tested from children under 4 years of age, none were positive. IMPORTANCE This study determined the percentages of both children and adult samples from the greater St. Louis metropolitan area who had antibodies to SARS-CoV-2 in late April to early May 2020. Approximately 1.7 to 3.1% of the tested individuals had antibodies, indicating that they had previously been infected by SARS-CoV-2. These results demonstrate that the extent of infection was about 10 times greater than the number of confirmed cases at that time. Furthermore, it demonstrated that by 5 years of age, children were infected to an extent similar to that of adults., (Copyright © 2021 Smith et al.)

Background: The position of Vice Chair of Education (VCE) is increasingly common in Surgery Departments. The role remains ill-defined. The purpose of this study was to explore perceptions of Department Chairs (DCs) and Other Education Stakeholders (OESs) regarding the VCE role., Methods: DCs and OESs at institutions with a VCE were surveyed. Descriptive statistics and cross-tabulations were calculated (SAS V9.4)., Results: The overall response rate was 25% (166/666). There were significant differences in whether DCs and OESs agree that the VCE supports others in fulfilling educational roles (95.2% vs 49.5%, p = 0.0002), is critical in achieving education missions (90.5% vs 56.6%, p = 0.0032), enhances the quality of education (95.3% vs 65.7%, p = 0.0174), and is important to education teams (95.0% vs 68.7%, p = 0.0464)., Conclusions: DCs value the VCE role more so than OESs, whom VCEs support. In order for VCEs to be effective educational leaders in Departments of Surgery, the needs of key stakeholders deserve further clarification., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: In-training examinations (ITEs) are intended for low-stakes, formative assessment of residents' knowledge, but are increasingly used for high-stake purposes, such as to predict board examination failures., Objective: The aim of this review was to investigate the relationship between performance on ITEs and board examination performance across medical specialties., Methods: A search of the literature for studies assessing the strength of the relationship between ITE and board examination performance from January 2000 to March 2019 was completed. Results were categorized based on the type of statistical analysis used to determine the relationship between ITE performance and board examination performance., Results: Of 1407 articles initially identified, 89 articles underwent full-text review, and 32 articles were included in this review. There was a moderate-strong relationship between ITE and board examination performance, and ITE scores significantly predict board examination scores for the majority of studies. Performing well on an ITE predicts a passing outcome for the board examination, but there is less evidence that performing poorly on an ITE will result in failing the associated specialty board examination., Conclusions: There is a moderate to strong correlation between ITE performance and subsequent performance on board examinations. That the predictive value for passing the board examination is stronger than the predictive value for failing calls into question the "common wisdom" that ITE scores can be used to identify "at risk" residents. The graduate medical education community should continue to exercise caution and restraint in using ITE scores for moderate to high-stakes decisions., Competing Interests: Conflict of interest: The authors declare they have no competing interests.

Background: The ACGME mandates that residency programs provide training related to high value care (HVC). The purpose of this study was to explore HVC education in general surgery residency programs., Methods: An electronic survey was distributed to general surgery residents in geographically diverse programs., Results: The response rate was 29% (181/619). Residents reported various HVC components in their curricula. Less than half felt HVC is very important for their future practice (44%) and only 15% felt confident they could lead a QI initiative in practice. Only 20% of residents reported participating in a root cause analysis and less than one-third of residents (30%) were frequently exposed to cost considerations., Conclusion: Few residents feel prepared to lead quality improvement initiatives, have participated in patient safety processes, or are aware of patients' costs of care. This underscores the need for improved scope and quality of HVC education and establishment of formal curricula., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Frailty is a syndrome where the ability to cope with acute physiological stress is compromised, although it is unclear what impact this stress has on long-term outcomes. Vascular-Physiological and Operative Severity Score for enumeration of Mortality and Morbidity is a validated method for calculating levels of stress associated with vascular procedures. We designed this study to evaluate the long-term impact of different levels of surgical stress among frail older patients undergoing vascular surgery procedures., Methods: We identified all independently living patients who underwent prospective frailty assessment followed by an elective vascular surgery procedure captured in the Vascular Quality Initiative registry (endovascular abdominal aortic aneurysm [AAA] repair, thoracic endovascular aortic repair, suprainguinal and infrainguinal bypass, peripheral vascular intervention, carotid endarterectomy, and open AAA) at an academic institution between January 2016 and July 2018. Patient- and procedure-level data were obtained from our institutional data warehouse and Vascular Quality Initiative database, and used to calculate Vascular-Physiological and Operative Severity Score for enumeration of Mortality and Morbidity scores. The association between frailty and composite outcome of any major complications (surgical site infection; graft thrombectomy; major amputation; adverse cardiac, pulmonary, or neurologic event; acute renal insufficiency; and/or reoperation related to the index procedure), nonhome living status, or death within 1 year after low-, medium-, and high-stress vascular procedures was evaluated using bivariate and logistic regression models., Results: A total of 163 patients were identified (70% male, mean age 67.8 years) who underwent open AAA repair (6%), endovascular AAA repair (21%), thoracic endovascular aortic repair (7%), suprainguinal bypass (5%), infrainguinal bypass (18%), carotid endarterectomy (18%), or peripheral vascular interventions (25%), which included 44 (27%) patients diagnosed with frailty before surgery. Overall, frail patients had significantly higher rates of the 1-year composite outcome (48% frail versus 27% nonfrail; P = 0.012) when compared with nonfrail patients, with a significant dose-dependent effect as the level of stress increased. In comparison, increasing levels of surgical stress had a negligible effect on long-term outcomes among nonfrail patients. The interaction between frailty and high surgical stress was found in adjusted regression models to be a significant predictor of adverse outcomes within 1 year after vascular surgery (odds ratio, 3.3; 95% confidence interval, 1.3-8.6; P < 0.01)., Conclusions: Frail patients who undergo high-stress vascular procedures have a significantly higher rate of complications leading to loss of functional independence and mortality within the year after their surgery. These data suggest that estimates of surgical stress should be incorporated into clinical decision making for frail older patients before and after surgery., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: High value care (HVC), maximizing quality while minimizing cost, has become a major focus of surgical practice. Effective education in healthcare value concepts is critical during residency to ensure graduates are able to deliver high value surgical care and participate in interprofessional teams to improve the system., Study Design: An HVC curriculum was implemented at a single academic medical center. Sixty-six residents from general surgery, plastic surgery, otolaryngology, and urology completed the curriculum over 3 academic years (2016 to 2019). The 1-year curriculum taught residents the concepts of HVC before participating in a value improvement project the following year. Residents' knowledge of value was assessed pre- and post-participation using a validated assessment tool, the Quality Improvement Knowledge Application Tool Revised (QIKAT-R), and a curriculum-specific assessment tool. The overall success of the program was evaluated by assessing residents' skills in completing value improvement projects using a novel scoring rubric., Results: After completing the program, residents expressed improved confidence in their ability to complete a value improvement project. Residents also demonstrated improved knowledge on the curriculum-specific assessment (4.7/13 to 10.9/13) and the scenario assessment using the QIKAT-R tool (8.5/27 to 16.4/27). As the program underwent iterative improvements each year, the quality of the residents' projects also improved, as assessed by the novel scoring rubric., Conclusions: Multimodal assessment demonstrated improvement in residents' objective knowledge of HVC principles, residents' ability to design and lead clinical value improvement projects, and residents' confidence they could use HVC principles in their current and future practice., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Over one third of general surgery residents interrupt their clinical training to pursue dedicated research time (DRT), which has financial implications for programs and residents. Studies have examined the impact of DRT on academic outcomes, but little is known about why residents pursue DRT. Therefore, this study aimed to examine resident motivations regarding DRT in order to gain an understanding of resident goals and challenges surrounding this phase of training., Design: Surgical residents currently participating in DRT and residents considering completing DRT were recruited to participate. Members of the research team at each institution conducted interviews and focus groups, which were recorded and transcribed. Data was analyzed using the qualitative method of open and focused coding. Identified themes guided the development of a conceptual framework., Setting: Interviews and focus groups were held at three geographically diverse US academic health centers., Participants: Twenty-one surgery residents participated., Results: Reasons for pursuing DRT fell into 1 of 3 themes: strategic career planning, professional development, and personal rejuvenation. Residents described the perceived need for publications or networking to enhance future competitiveness for desired fellowships or academic appointments. Residents also expressed the desire to have time for career exploration and to cultivate mentorship for their professional career. The need to take time off for more personal reasons, including burnout, was pervasive. Additionally, many in DRT felt under-supported in developing their research skills and expressed a desire for more formal instruction and guidance from mentors., Conclusions: General surgery residents' motivations to pursue DRT are multifactorial. Professional development is a pervasive motivation and includes learning skills that can be applied to future research. Current DRT programs may be inadequate in supporting residents to achieve this goal. These results can be used to inform programmatic efforts to optimize DRT for residents and mentors alike., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Proper insulin injection technique has demonstrated positive clinical outcomes in patients with diabetes. A Canadian-based practice reflective was undertaken to evaluate the current state of understanding of injection technique practices by patients administering insulin, and the importance physicians place on proper injection technique., Methods: Twenty-four sites across Canada completed a practice profile survey and enrolled adult non-pregnant patients with either type 1 or type 2 diabetes injecting insulin using an insulin pen. Seven areas of proper injection technique to be evaluated were identified by the study steering committee: size of injection site, use of a skin lift, needle reuse, length of the needle, duration of the needle in the skin, injection into lipohypertrophic tissue, and applied injection force. During a scheduled visit, each patient filled out the Injection Technique Survey and the physician documented the answers via an electronic database., Results: Almost all physicians surveyed agreed (96%) that proper insulin injection technique is important or very important and 80% indicated they were either completely confident or fairly confident in discussing overall insulin injection technique. All patients surveyed were making at least one insulin injection technique error within the following categories: applied injection force (76%), area size of injection site (64%), duration of pen needle in skin (61%), pen needle reuse (39%), performs a skin lift with a 4 or 5 mm needle (38%), uses a longer pen needle than required (34%), and injection of insulin into lipohypertrophic tissue (37%)., Conclusion: Patients commonly make insulin injection errors. Patient and physician education on optimal insulin injection technique continues to be an unmet medical need for the treatment of patients with diabetes. Prospective trials examining the impact of new technology, diabetes educational teams, and e-learning as educational interventions are potential avenues to explore in future studies to support improved insulin injection technique.

Objective: To determine the quality improvement (QI) experiences of urology residents in the United States., Materials and Methods: An Institutional Review Board approved national survey of Urology residents was administered in June 2019. The survey instrument sought to understand QI curricular methods and experiences of urology residents as well as their knowledge of QI fundamentals., Results: Of 465 invited residents, 159 (34%) responded. Respondents represented all 8 AUA sections. The majority of respondents self-identified as white (66%). Females made up 30% of respondents. Less than 1/3 of residents (32%) report use of online modules, whereas nearly 2/3 (63%) report lecture-based didactics. Fifteen percent of residents report no QI curriculum. While nearly 2/3 of residents report receiving training in QI principles (64%), far less report receiving training in how to apply QI methodology (44%). Only 29% of residents report being required to lead a QI project. No differences were seen by training level. Only 3 respondents had heard of the Institute of Medicine's aims for quality improvement. Respondents had better knowledge of process, balancing and outcome measures, but less than half of respondents (49%) were able to correctly identify all 3. Having any QI curriculum is associated with correctly answering knowledge questions (P = .03)., Conclusion: From a resident perspective, urology residency programs currently provide QI curricula that are inadequate to ensure residents achieve Accreditation Council for Graduate Medical Education milestones. It is imperative the urology community as a whole address these curricular gaps to ensure graduates are prepared to deliver high-quality, cost-conscious care to their patients once in practice., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The coronavirus disease 2019 pandemic has made deployment of an effective vaccine a global health priority. We evaluated the protective activity of a chimpanzee adenovirus-vectored vaccine encoding a prefusion stabilized spike protein (ChAd-SARS-CoV-2-S) in challenge studies with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mice expressing the human angiotensin-converting enzyme 2 receptor. Intramuscular dosing of ChAd-SARS-CoV-2-S induces robust systemic humoral and cell-mediated immune responses and protects against lung infection, inflammation, and pathology but does not confer sterilizing immunity, as evidenced by detection of viral RNA and induction of anti-nucleoprotein antibodies after SARS-CoV-2 challenge. In contrast, a single intranasal dose of ChAd-SARS-CoV-2-S induces high levels of neutralizing antibodies, promotes systemic and mucosal immunoglobulin A (IgA) and T cell responses, and almost entirely prevents SARS-CoV-2 infection in both the upper and lower respiratory tracts. Intranasal administration of ChAd-SARS-CoV-2-S is a candidate for preventing SARS-CoV-2 infection and transmission and curtailing pandemic spread., Competing Interests: Declaration of Interests M.S.D. is a consultant for Inbios, Vir Biotechnology, and NGM Biopharmaceuticals and on the Scientific Advisory Board of Moderna. The Diamond laboratory has received unrelated funding support from Moderna, Vir Biotechnology, and Emergent BioSolutions. M.S.D., D.T.C., A.O.H., and I.P.D. have filed a disclosure with Washington University for possible development of ChAd-SARS-CoV-2. M.J.H. is a member of the DSMB for AstraZeneca and founder of NuPeak Therapeutics. The Baric laboratory has received unrelated funding support from Takeda, Pfizer, and Eli Lilly., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: During the COVID-19 pandemic, central venous access line teams were implemented at many hospitals throughout the world to provide access for critically ill patients. The objective of this study was to describe the structure, practice patterns, and outcomes of these vascular access teams during the COVID-19 pandemic., Methods: We conducted a cross-sectional, self-reported study of central venous access line teams in hospitals afflicted with the COVID-19 pandemic. To participate in the study, hospitals were required to meet one of the following criteria: development of a formal plan for a central venous access line team during the pandemic; implementation of a central venous access line team during the pandemic; placement of central venous access by a designated practice group during the pandemic as part of routine clinical practice; or management of an iatrogenic complication related to central venous access in a patient with COVID-19., Results: Participants from 60 hospitals in 13 countries contributed data to the study. Central venous line teams were most commonly composed of vascular surgery and general surgery attending physicians and trainees. Twenty sites had 2657 lines placed by their central venous access line team or designated practice group. During that time, there were 11 (0.4%) iatrogenic complications associated with central venous access procedures performed by the line team or group at those 20 sites. Triple lumen catheters, Cordis (Santa Clara, Calif) catheters, and nontunneled hemodialysis catheters were the most common types of central venous lines placed by the teams. Eight (14%) sites reported experience in placing central venous lines in prone, ventilated patients with COVID-19. A dedicated line cart was used by 35 (59%) of the hospitals. Less than 50% (24 [41%]) of the participating sites reported managing thrombosed central lines in COVID-19 patients. Twenty-three of the sites managed 48 iatrogenic complications in patients with COVID-19 (including complications caused by providers outside of the line team or designated practice group)., Conclusions: Implementation of a dedicated central venous access line team during a pandemic or other health care crisis is a way by which physicians trained in central venous access can contribute their expertise to a stressed health care system. A line team composed of physicians with vascular skill sets provides relief to resource-constrained intensive care unit, ward, and emergency medicine teams with a low rate of iatrogenic complications relative to historical reports. We recommend that a plan for central venous access line team implementation be in place for future health care crises., (Copyright © 2020 Society for Vascular Surgery. All rights reserved.)

Leptospirosis is a neglected zoonotic disease affecting mostly the world's tropical regions. The rural people of northeastern Thailand suffer from a large number of leptospirosis infections, and their abundant rice fields are optimal rodent habitats. To evaluate the contribution of diversity and carriage rate of pathogenic Leptospira in rodent reservoirs to leptospirosis incidence, we surveyed rodents, between 2011 and 2012, in four provinces in northeastern Thailand with the highest incidence rates of human leptospirosis cases. We used lipL32 real-time PCR to detect pathogenic Leptospira in rodent kidneys, partial 16S rRNA gene sequencing to classify the infecting Leptospira species, and whole 16S rDNA sequencing to classify species of isolated Leptospira . Overall prevalence of Leptospira infection was 3.6% (18/495). Among infected rodents, Bandicota indica (14.3%), Rattus exulans (3.6%), and R . rattus (3.2%) had renal carriage. We identified two pathogenic Leptospira species: L . interrogans ( n = 15) and L . borgpetersenii ( n = 3). In addition, an L . wolffii (LS0914U) isolate was recovered from the urine of B . indica . Leptospira infection was more prevalent in low density rodent populations, such as B . indica . In contrast, there was a lower prevalence of Leptospira infection in high density rodent populations of R . exulans and R . rattus .

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections, and an effective vaccine is critical to mitigate coronavirus-induced disease 2019 (COVID-19). Previously, we developed a replication-competent vesicular stomatitis virus (VSV) expressing a modified form of the SARS-CoV-2 spike gene in place of the native glycoprotein gene (VSV-eGFP-SARS-CoV-2). Here, we show that vaccination with VSV-eGFP-SARS-CoV-2 generates neutralizing immune responses and protects mice from SARS-CoV-2. Immunization of mice with VSV-eGFP-SARS-CoV-2 elicits high antibody titers that neutralize SARS-CoV-2 and target the receptor binding domain that engages human angiotensin-converting enzyme-2 (ACE2). Upon challenge with a human isolate of SARS-CoV-2, mice that expressed human ACE2 and were immunized with VSV-eGFP-SARS-CoV-2 show profoundly reduced viral infection and inflammation in the lung, indicating protection against pneumonia. Passive transfer of sera from VSV-eGFP-SARS-CoV-2-immunized animals also protects naive mice from SARS-CoV-2 challenge. These data support development of VSV-SARS-CoV-2 as an attenuated, replication-competent vaccine against SARS-CoV-2., Competing Interests: Declaration of Interests M.S.D. is a consultant for Inbios, Vir Biotechnology, and NGM Biopharmaceuticals and is on the Scientific Advisory Board of Moderna. M.J.H. is a member of the Data and Safety Monitoring Board for AstroZeneca and founder of NuPeak Therapeutics. The Diamond laboratory has received funding under sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. The Whelan laboratory has received funding under sponsored research agreements from Vir Biotechnology. S.P.J.W., P.W.R., M.S.D., and J.B.C. have filed a disclosure with Washington University for the recombinant VSV., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Long-chain fatty acids (LCFAs) play important roles in cellular energy metabolism, acting as both an important energy source and signalling molecules 1 . LCFA-CoA esters promote their own oxidation by acting as allosteric inhibitors of acetyl-CoA carboxylase, which reduces the production of malonyl-CoA and relieves inhibition of carnitine palmitoyl-transferase 1, thereby promoting LCFA-CoA transport into the mitochondria for β-oxidation 2-6 . Here we report a new level of regulation wherein LCFA-CoA esters per se allosterically activate AMP-activated protein kinase (AMPK) β1-containing isoforms to increase fatty acid oxidation through phosphorylation of acetyl-CoA carboxylase. Activation of AMPK by LCFA-CoA esters requires the allosteric drug and metabolite site formed between the α-subunit kinase domain and the β-subunit. β1 subunit mutations that inhibit AMPK activation by the small-molecule activator A769662, which binds to the allosteric drug and metabolite site, also inhibit activation by LCFA-CoAs. Thus, LCFA-CoA metabolites act as direct endogenous AMPK β1-selective activators and promote LCFA oxidation.

Wearable sensors are beneficial for continuous health monitoring, movement analysis, rehabilitation, evaluation of human performance, and for fall detection. Wearable stretch sensors are increasingly being used for human movement monitoring. Additionally, falls are one of the leading causes of both fatal and nonfatal injuries in the workplace. The use of wearable technology in the workplace could be a successful solution for human movement monitoring and fall detection, especially for high fall-risk occupations. This paper provides an in-depth review of different wearable stretch sensors and summarizes the need for wearable technology in the field of ergonomics and the current wearable devices used for fall detection. Additionally, the paper proposes the use of soft-robotic-stretch (SRS) sensors for human movement monitoring and fall detection. This paper also recapitulates the findings of a series of five published manuscripts from ongoing research that are published as Parts I to V of "Closing the Wearable Gap" journal articles that discuss the design and development of a foot and ankle wearable device using SRS sensors that can be used for fall detection. The use of SRS sensors in fall detection, its current limitations, and challenges for adoption in human factors and ergonomics are also discussed., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Objective: Social determinants may negatively affect health via Hypothalamic-Pituitary-Adrenal (HPA) axis dysfunction. The potential contribution of social determinants and related factors to HPA-axis functioning is important to study among African American adults, who are more likely to experience societal inequities and health disparities relative to other racial/ethnic groups. This study examined the relationship between depressive symptoms and perceived social control on HPA-axis functioning among African American adults., Method: Participants (N = 107; Mage = 50, 79% female) were administered measures including the Center for Epidemiologic Studies-Depression and Informal (neighborhood) Social Control. Study procedures included the provision of 6 saliva samples for cortisol analysis (at wakeup, 30- and 90-min post-wakeup, 2:00 PM, 5:00 PM, and prebedtime). The relationship between depression and social control on the functioning of the HPA-axis were simultaneously examined within a 2-level hierarchical linear model., Results: Variability in the Cortisol Awakening Response (CAR) was accounted for by depressive symptomatology (p = .023) and perceived social control (p = .016), whereby greater depression was associated with a blunted CAR (less awakening cortisol production) and greater perceptions of neighborhood social control with a higher CAR., Conclusions: Elevated depressive symptoms and low perceptions of neighborhood social control may serve as mechanisms that help to explain within-group variability in the functioning of stress physiology among African American adults. Findings enhance understanding of how social determinants may affect African Americans' health. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Background: Dengue is an important arboviral disease with about 100 million dengue cases per year, of which, ~5% result in severe disease. Clinical differentiation of dengue from other acute febrile illnesses (AFI) is difficult, and diagnostic blood tests are costly. We evaluated the utility of anti-DENV IgM in urine to identify dengue cases among AFI patients enrolled in a clinical study., Methods: Between May 2012-March 2013, 1538 study participants with fever for ≤7 days were enrolled, a medical history was obtained, and serum and urine specimens were collected. Serum was tested for DENV RNA and anti-DENV IgM. Urine was tested for anti-DENV IgM, and its sensitivity and specificity to detect sera laboratory-positive dengue cases were calculated. We evaluated if urine anti-DENV IgM positivity early (≤5 days post-illness onset [DPO]) and late (6-14 DPO) in the clinical course was associated with dengue severity., Results: Urine anti-DENV IgM sensitivity and specificity were 47.4% and 98.5%, respectively, when compared with serum anti-DENV IgM ELISA results, and 29.7% and 91.1% when compared with serum rRT-PCR results. There was no correlation between urine anti-DENV IgM positivity and patient sex or pre-existing chronic disease. Early in the clinical course, a significantly higher proportion of those who developed dengue with warning signs had anti-DENV IgM in their urine when compared to those without warning signs (20.4% vs. 4.3%). There was no difference in the proportion with urine anti-DENV IgM positivity between severity groups late in the clinical course., Conclusion: While detection of urine anti-DENV IgM lacked adequate diagnostic sensitivity, it is a highly specific marker for laboratory-positive dengue, and its presence early in the clinical course may distinguish those with more severe disease. Further assessment of urine anti-DENV IgM by DPO is warranted to determine its utility as an early diagnostic (and possibly prognostic) marker for dengue., Competing Interests: The authors have declared that no competing interests exist.

Background: Integrated vascular surgery residency, or "0+5," programs provide education in the Accreditation Council for Graduate Medical Education (ACGME) competencies of Systems-Based Practice (SBP) and Practice-Based Learning and Improvement (PBLI), which include milestones related to quality improvement (QI). It is unclear what QI curricula are in place in 0+5 programs nationally or how 0+5 residents perceive the importance of QI., Objective: The purpose of this study is to assess current 0+5 residents' knowledge, experiences with, and attitudes about QI., Design: A survey was developed using the ACGME Common Program Requirements and Milestones pertaining to QI. All 0+5 residents from 2017 to 2018 academic year were emailed an electronic link to the survey. Descriptive statistics and cross-tabulations were calculated using Stata/MP version 13.1., Setting: All 0+5 vascular surgery residency programs in the United State (n = 52)., Participants: The survey was completed by 35% (n = 90/257) of 0+5 residents, representing 75% of 0+5 programs in the United States (n = 39/52)., Results: Forty-one percent of respondents felt that applying QI methods is very important and 33% felt that QI education is very important for their future work, however, just 13% felt very prepared to lead a QI initiative. Residents' perceptions of preparedness to lead QI projects and the importance they attached to QI education were significantly influenced by their participation in a QI project (p = 0.003 and p = 0.038 respectively). Finally, just 8% (n = 6) of residents responded correctly to all 13 knowledge-based questions and these residents felt better prepared to lead a QI initiative compared to those who answered incorrectly (p = 0.002)., Conclusions: Most 0+5 residents report participation in a QI project during residency, however, few feel prepared to lead a QI initiative in practice. Furthermore, only half of PGY5 0+5 residents report achieving specific ACGME targets for graduation pertaining to QI. Current QI curricula in 0+5 programs may be inadequate in teaching fundamental QI concepts and achieving ACGME competency targets for graduation., (Copyright © 2019 Association of Program Directors in Surgery. All rights reserved.)

Pompe disease (glycogen storage disease type II) is caused by mutations in acid α-glucosidase (GAA) resulting in lysosomal pathology and impairment of the muscular and cardio-pulmonary systems. Enzyme replacement therapy (ERT), the only approved therapy for Pompe disease, improves muscle function by reducing glycogen accumulation but this approach entails several limitations including a short drug half-life and an antibody response that results in reduced efficacy. To address these limitations, new treatments such as gene therapy are under development to increase the intrinsic ability of the affected cells to produce GAA. Key components to gene therapy strategies include the choice of vector, promoter, and the route of administration. The efficacy of gene therapy depends on the ability of the vector to drive gene expression in the target tissue and also on the recipient's immune tolerance to the transgene protein. In this review, we discuss the preclinical and clinical studies that are paving the way for the development of a gene therapy strategy for patients with early and late onset Pompe disease as well as some of the challenges for advancing gene therapy.

Objective: To determine the effects of perioperative high (80%) versus low (30%) fraction of inspired oxygen (FiO 2 ) on surgical site infection (SSI) and mortality in adult surgical patients., Background: The routine use of high fraction perioperative oxygen in patients is "standard of care" and recommended by the World Health Organisation; however, whether there is truly any benefit to this therapy has been challenged by some authors. Questions have also been raised about the possibility of harm from oxygen therapy., Method: Randomised control trials comparing high-to-low FiO 2 were located by searching MEDLINE, Embase, CENTRAL and Web of Science. The primary outcomes were SSI up to 15 days and up to any time point postoperatively and mortality up to 30 days. The data were analysed using random effects meta-analysis., Results: Twelve studies involving 10,212 participants were included. At 15 days postoperatively, and at the longest point of post-operative follow-up, there was no statistically significant reduction in the risk of SSI when comparing patients who received a perioperative FiO 2 of 30% to those with an FiO 2 of 80% (RR 1.41, 95% CI 1.00-2.01, p 0.05 and RR 1.23, 95% CI 1.00-1.51, p 0.05). There was no statistically significant difference in mortality between the 30% FiO 2 and the 80% FiO 2 groups (RR 1.12, 95% CI 0.56-2.22, p 0.76)., Conclusion: This meta-analysis showed no statistically significant difference in post-operative SSI or mortality when comparing patients receiving an FiO 2 of 80% to those receiving an FiO 2 of 30%.

The purpose of this study was to evaluate the use of compressible soft robotic sensors (C-SRS) in determining plantar pressure to infer vertical and shear forces in wearable technology: A ground reaction pressure sock (GRPS). To assess pressure relationships between C-SRS, pressure cells on a BodiTrak TM Vector Plate, and Kistler TM Force Plates, thirteen volunteers performed three repetitions of three different movements: squats, shifting center-of-pressure right to left foot, and shifting toes to heels with C-SRS in both anterior-posterior (A/P) and medial-lateral (M/L) sensor orientations. Pearson correlation coefficient of C-SRS to BodiTrak TM Vector Plate resulted in an average R-value greater than 0.70 in 618/780 (79%) of sensor to cell comparisons. An average R-value greater than 0.90 was seen in C-SRS comparison to Kistler TM Force Plates during shifting right to left. An autoregressive integrated moving average (ARIMA) was conducted to identify and estimate future C-SRS data. No significant differences were seen in sensor orientation. Sensors in the A/P orientation reported a mean R 2 value of 0.952 and 0.945 in the M/L sensor orientation, reducing the effectiveness to infer shear forces. Given the high R values, the use of C-SRSs to infer normal pressures appears to make the development of the GRPS feasible.

Maximal inspiratory pressure (PI MAX ) reflects inspiratory weakness in late-onset Pompe disease (LOPD). However, static pressure tests may not reveal specific respiratory muscle adaptations to disruptions in breathing. We hypothesized that dynamic respiratory muscle functional tests reflect distinct ventilatory compensations in LOPD. We evaluated LOPD (n = 7) and healthy controls (CON, n = 7) during pulmonary function tests, inspiratory endurance testing, dynamic kinematic MRI of the thorax, and ventilatory adjustments to single-breath inspiratory loads (inspiratory load compensation, ILC). We observed significantly lower static and dynamic respiratory function in LOPD. PI MAX , spirometry, endurance time, and maximal diaphragm descent were significantly correlated. During single-breath inspiratory loads, inspiratory time and airflow acceleration increased to preserve volume, and in LOPD, the response magnitudes correlated to maximal chest wall kinematics. The results indicate that changes in diaphragmatic motor function and strength among LOPD subjects could be detected through dynamic respiratory testing. We concluded that neuromuscular function significantly influenced breathing endurance, timing and loading compensations.

Metformin is the most commonly prescribed medication for type 2 diabetes, owing to its glucose-lowering effects, which are mediated through the suppression of hepatic glucose production (reviewed in refs. 1-3 ). However, in addition to its effects on the liver, metformin reduces appetite and in preclinical models exerts beneficial effects on ageing and a number of diverse diseases (for example, cognitive disorders, cancer, cardiovascular disease) through mechanisms that are not fully understood 1-3 . Given the high concentration of metformin in the liver and its many beneficial effects beyond glycemic control, we reasoned that metformin may increase the secretion of a hepatocyte-derived endocrine factor that communicates with the central nervous system 4 . Here we show, using unbiased transcriptomics of mouse hepatocytes and analysis of proteins in human serum, that metformin induces expression and secretion of growth differentiating factor 15 (GDF15). In primary mouse hepatocytes, metformin stimulates the secretion of GDF15 by increasing the expression of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP; also known as DDIT3). In wild-type mice fed a high-fat diet, oral administration of metformin increases serum GDF15 and reduces food intake, body mass, fasting insulin and glucose intolerance; these effects are eliminated in GDF15 null mice. An increase in serum GDF15 is also associated with weight loss in patients with type 2 diabetes who take metformin. Although further studies will be required to determine the tissue source(s) of GDF15 produced in response to metformin in vivo, our data indicate that the therapeutic benefits of metformin on appetite, body mass and serum insulin depend on GDF15.

Objective: Duchenne muscular dystrophy (DMD) is characterized by damage to muscles including the muscles involved in respiration. Dystrophic muscles become weak and infiltrated with fatty tissue, resulting in progressive respiratory impairment. The objective of this study was to assess respiratory muscle quality and function in DMD using magnetic resonance imaging and to determine the relationship to clinical respiratory function., Methods: Individuals with DMD (n = 36) and unaffected controls (n = 12) participated in this cross sectional magnetic resonance imaging study. Participants underwent dynamic imaging of the thorax to assess diaphragm and chest wall mobility and chemical shift-encoded imaging of the chest and abdomen to determine fatty infiltration of the accessory respiratory muscles. Additionally, clinical pulmonary function measures were obtained., Results: Thoracic cavity area was decreased in individuals with DMD compared to controls during tidal and maximal breathing. Individuals with DMD had reduced chest wall movement in the anterior-posterior direction during maximal inspirations and expirations, but diaphragm descent during maximal inspirations (normalized to height) was only decreased in a subset of individuals with maximal inspiratory pressures less than 60% predicted. Muscle fat fraction was elevated in all three expiratory muscles assessed (p < 0.001), and the degree of fatty infiltration correlated with percent predicted maximal expiratory pressures (r =  - 0.70, p < 0.001). The intercostal muscles demonstrated minimal visible fatty infiltration; however, this analysis was qualitative and resolution limited., Interpretation: This magnetic resonance imaging investigation of diaphragm movement, chest wall movement, and accessory respiratory muscle fatty infiltration provides new insights into the relationship between disease progression and clinical respiratory function.

Objective: Frailty and sarcopenia are related but independent conditions commonly diagnosed in older patients that can be used to assess their ability to tolerate the stress of major vascular surgery. For surgical decision-making, however, it is important to know the prognostic implications associated with each of these conditions. The study was designed to assess the association of frailty and sarcopenia phenotypes with long-term survival of patients undergoing surgical and nonsurgical management of vascular disease., Methods: We retrospectively reviewed all patients presenting to the vascular surgery clinic at an academic hospital between December 2015 and August 2017 who underwent prospective frailty assessment with the Clinical Frailty Scale and who had abdominal computed tomography (CT) scans performed within the preceding 12 months. A single axial CT image at the caudal end of the third lumbar vertebra was assessed to measure cross-sectional areas of skeletal muscle. Sarcopenia was defined by established criteria specific for male and female patients. After patients were stratified by frailty and sarcopenia diagnoses along with comorbidities, the association with all-cause mortality was analyzed by Kaplan-Meier curves and Cox regression models., Results: A total of 415 patients underwent both frailty and sarcopenia assessment, of whom 112 (27%) met sarcopenia criteria alone, 48 (12%) met only frailty criteria, and 56 (13%) met criteria for both phenotypes. There were 199 (48%) controls who met neither criterion. Vascular operations were performed in 167 (40%) patients after frailty and sarcopenia assessment, whereas 248 (60%) patients were managed nonoperatively with median (interquartile range) follow-up after CT imaging of 1.5 (1.1-2.2) years. Patients diagnosed with either phenotype were older (mean, 65 years vs 59 years; P < .001) and more likely to be male (69% vs 54%; P < .001) compared with patients without sarcopenia or frailty. Long-term survival was significantly decreased for patients diagnosed with either frailty alone or frailty and sarcopenia who underwent surgical or nonsurgical management (log-rank, P < .001 for both comparisons). In multivariate regression models, however, frailty was the only independent variable (hazard ratio, 7.7; 95% confidence interval, 3.2-18.7; P < .001) that predicted mortality., Conclusions: Frailty and sarcopenia overlap to varying degrees in patients presenting to vascular surgery clinics and can be used alone or in combination to predict long-term survival of older patients. However, our data indicate that it was only the diagnosis of frailty that was an independent predictor of mortality and had the strongest prognostic significance in patients undergoing both surgical and nonoperative management., (Published by Elsevier Inc.)

The linearity of soft robotic sensors (SRS) was recently validated for movement angle assessment using a rigid body structure that accurately depicted critical movements of the foot-ankle complex. The purpose of this study was to continue the validation of SRS for joint angle movement capture on 10 participants (five male and five female) performing ankle movements in a non-weight bearing, high-seated, sitting position. The four basic ankle movements-plantar flexion (PF), dorsiflexion (DF), inversion (INV), and eversion (EVR)-were assessed individually in order to select good placement and orientation configurations (POCs) for four SRS positioned to capture each movement type. PF, INV, and EVR each had three POCs identified based on bony landmarks of the foot and ankle while the DF location was only tested for one POC. Each participant wore a specialized compression sock where the SRS could be consistently tested from all POCs for each participant. The movement data collected from each sensor was then compared against 3D motion capture data. R -squared and root-mean-squared error averages were used to assess relative and absolute measures of fit to motion capture output. Participant robustness, opposing movements, and gender were also used to identify good SRS POC placement for foot-ankle movement capture.

Pompe disease is a neuromuscular disease caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase leading to lysosomal and cytoplasmic glycogen accumulation in neurons and striated muscle. In the decade since availability of first-generation enzyme replacement therapy (ERT) a better understanding of the clinical spectrum of disease has emerged. The most severe form of early onset disease is typically identified with symptoms in the first year of life, known as infantile-onset Pompe disease (IOPD). Infants are described at floppy babies with cardiac hypertrophy in the first few months of life. A milder form with late onset (LOPD) of symptoms is mostly free of cardiac involvement with slower rate of progression. Glycogen accumulation in the CNS and skeletal muscle is observed in both IOPD and LOPD. In both circumstances, multi-system disease (principally motoneuron and myopathy) leads to progressive weakness with associated respiratory and feeding difficulty. In IOPD the untreated natural history leads to cardiorespiratory failure and death in the first year of life. In the current era of ERT clinical outcomes are improved, yet, many patients have an incomplete response and a substantial unmet need remains. Since the neurological manifestations of the disease are not amenable to peripheral enzyme replacement, we set out to better understand the pathophysiology and potential for treatment of disease manifestations using adeno-associated virus (AAV)-mediated gene transfer, with the first clinical gene therapy studies initiated by our group in 2006. This review focuses on the preclinical studies and clinical study findings which are pertinent to the development of a comprehensive gene therapy strategy for both IOPD and LOPD. Given the advent of newborn screening, a significant focus of our recent work has been to establish the basis for repeat administration of AAV vectors to enhance neuromuscular therapeutic efficacy over the life span., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: The 0+5 integrated vascular surgery residency program (IVSR) was introduced as a training model toward board certification in vascular surgery over 10 years ago. The pros and cons of this training model have been debated., Objective: The purpose of this review is to investigate, using qualitative methods, what is known about the development, implementation, and outcomes of the IVSR paradigm., Design: A systematic search of the literature pertaining to the IVSR training model was conducted to include literature from 2005 to 2016. A search strategy involving use of 4 literature databases, 4 search terms, and 4 inclusion criteria was used. Three independent reviewers screened titles and abstracts for inclusion. Data abstraction was performed by 1 reviewer. Qualitative content analysis was completed using the method of constant comparative analysis associated with a grounded theory design by all 3 reviewers., Results: Of 890 articles initially identified, 33 articles were found to meet inclusion criteria for full review. Nineteen (57%) were research articles with an average Medical Education Research Study Quality Instrument score of 6.3 out of 18. The remaining articles were categorized as editorials, presidential addresses, invited commentaries, and historical summaries. Three major themes related to the IVSR program were identified: context of program development, processes of the program once implemented, and outcomes., Conclusions: The literature on the IVSR paradigm reflects contextual, process, and outcome issues. Research articles are of generally low quality and there is a paucity of analyses of outcome issues. Further research is recommended to identify and understand the outcomes of the model., (Copyright © 2019 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Mxra8 is a receptor for multiple arthritogenic alphaviruses that cause debilitating acute and chronic musculoskeletal disease in humans. Herein, we present a 2.2 Å resolution X-ray crystal structure of Mxra8 and 4 to 5 Å resolution cryo-electron microscopy reconstructions of Mxra8 bound to chikungunya (CHIKV) virus-like particles and infectious virus. The Mxra8 ectodomain contains two strand-swapped Ig-like domains oriented in a unique disulfide-linked head-to-head arrangement. Mxra8 binds by wedging into a cleft created by two adjacent CHIKV E2-E1 heterodimers in one trimeric spike and engaging a neighboring spike. Two binding modes are observed with the fully mature VLP, with one Mxra8 binding with unique contacts. Only the high-affinity binding mode was observed in the complex with infectious CHIKV, as viral maturation and E3 occupancy appear to influence receptor binding-site usage. Our studies provide insight into how Mxra8 binds CHIKV and creates a path for developing alphavirus entry inhibitors., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: While factors leading to hypoventilation have been well studied in Pompe disease, cough effectiveness and airway clearance practices are less understood. We aimed to identify significant factors that influence peak cough flow (PCF) in Pompe, and to detect whether pulmonary hygiene practices were reflective of reduced PCF., Methods: This is a prospective observational study of 20 subjects with Pompe disease (infantile-onset: 7, juvenile-onset: 6, adult-onset: 14). Subjects performed spirometry, maximal respiratory pressures, and cough (voluntary: n = 24, spontaneous: n = 3). Subjects or their parents reported airway clearance and secretion management practices. Relationships between disease variables, pulmonary function, and cough parameters as well as group differences in cough parameters were evaluated., Results: Subjects with infantile-onset disease had significantly lower PCF (p < 0.05) and tended to require more external ventilatory support (p = 0.07). In juvenile- and adult-onset disease, PCF differed according to external ventilatory requirement [daytime: 83.6 L/min (95% CI 41.2-126.0); nighttime: 224.6 L/min (95% CI 139.1-310.2); none: 340.2 L/min (95% CI 193.3-487.6), p < 0.005]. Cough inspiratory volume also differed significantly by ventilatory requirement [daytime: 5.5 mL/kg (95% CI 3.0-8.0); nighttime: 16.0 mL/kg (95% CI 11.8-20.2); none: 26.8 mL/kg (95% CI 11.9-41.7), p < 0.001]. However, routine airway clearance or secretion management practices were only consistently reported among patients with infantile-onset disease (infantile: 86%, juvenile: 0%, adult: 14%, p < 0.005)., Conclusions: Cough weakness was detected in the majority of patients with Pompe disease and was influenced by both inspiratory and expiratory muscle function. Patients at risk for problems or with ineffective PCF should be urged to complete routine pulmonary hygiene.

Patients with impending respiratory failure often require mechanical ventilation to optimize gas exchange. Although this form of assisted ventilation is required for survival, its persistent use results in diaphragm weakness and muscle fiber atrophy. There is strong evidence that mechanical ventilation alters the structure and function of the diaphragm, resulting in prolonged dependence on assisted ventilation and long-term consequences such as a delayed functional recovery, reduced quality of life and increased risk of mortality. This review summarizes the mechanisms underlying diaphragm dysfunction due to prolonged mechanical ventilation, highlights the role of inspiratory muscle exercise as a strategy to counter diaphragm weakness, and identifies the parameters of an evidence-supported exercise prescription for difficult to wean patients., Competing Interests: Notification of Conflicts of Interest: ADM is an external consultant for Lungpacer, which is developing an intravenous phrenic nerve pacing system.

Background: Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease characterized by progressive muscle weakness, multiple system involvement and premature mortality. Effective treatments for DMD through clinical trials and natural history studies are currently underway. Clinical trials in DMD typically include several outcome measures of motor function. Research sites and studies have been found to have slightly different operational definitions for a given functional outcome resulting in different procedures and protocols for these measurements., Objective: The goal of this study is to establish agreement among experts in the field around best practices in collecting functional outcome data in DMD providing researchers and clinicians with guidance on best practices., Methods: A group of 30 experts in Duchenne Muscular Dystrophy (DMD) with experience in the development and/ or execution of lower extremity outcome measures for this population met face to face to identify incongruences in the collection of this data. This effort was based in the United States (US) and sponsored by Parent Project Muscular Dystrophy. Several discrepancies were categorized for each outcome which included: 6-minute walk test, 10-meter walk/run, supine to stand, ascend 4 stairs, sit to stand, and the NorthStar Ambulatory Assessment. Following this meeting an additional 32 experts in DMD (28 from the United States and 11 international participants) consented to participate in a Delphi Survey to reach consensus on the protocols and execution of lower extremity outcomes., Results: Round one: 70 operationally defined questions were surveyed with 45 (64%) reaching >70% consensus. Round two: 27 questions were operational, with 20 (74%) reaching >70% consensus. Those questions that did not reach consensus appear minor., Conclusion: With minor modifications in the collection of data across sites, outcomes could potentially be normalized across research studies. This would reduce excessive training for evaluators in trials and produce minimal differences between protocols. Consistency in protocols will promote more efficient study start up, less errors between administration of items across studies, and ultimately improve quality and reliability of the functional outcomes. The authors strongly advocate for the establishment of a "research network library" that could be utilized by all those performing clinical assessments and trials in DMD.

Objective: Frailty, a clinical syndrome associated with loss of metabolic reserves, is prevalent among patients who present to vascular surgery clinics for evaluation. The Clinical Frailty Scale (CFS) is a rapid assessment method shown to be highly specific for identifying frail patients. In this study, we sought to evaluate whether the preoperative CFS score could be used to predict loss of independence after major vascular procedures., Methods: We identified all patients living independently at home who were prospectively assessed using the CFS before undergoing an elective major vascular surgery procedure (admitted for >24 hours) at an academic medical center between December 2015 and December 2017. Patient- and procedure-level clinical data were obtained from our institutional Vascular Quality Initiative registry database. The composite outcome of discharge to a nonhome location or 30-day mortality was evaluated using bivariate and multivariate regression models., Results: A total of 134 independent patients were assessed using the CFS before they underwent elective open abdominal aortic aneurysm repair (8%), endovascular aneurysm repair (26%), thoracic endovascular aortic repair (6%), suprainguinal bypass (6%), infrainguinal bypass (16%), carotid endarterectomy (19%), or peripheral vascular intervention (20%). Among 39 (29%) individuals categorized as being frail using the CFS, there was no significant difference in age or American Society of Anesthesiologists physical status compared with nonfrail patients. However, frail patients were significantly more likely to need mobility assistance after surgery (62% frail vs 22% nonfrail; P < .01) and to be discharged to a nonhome location (22% frail vs 6% nonfrail; P = .01) or to die within 30 days after surgery (8% frail vs 0% nonfrail; P < .01). Preoperative frailty was associated with a >12-fold higher risk (odds ratio, 12.1; 95% confidence interval, 2.17-66.96; P < .01) of 30-day mortality or loss of independence, independent of the vascular procedure undertaken., Conclusions: The CFS is a practical tool for assessing preoperative frailty among patients undergoing elective major vascular surgery and can be used to predict likelihood of requiring discharge to a nursing facility or death after surgery. The identification of frail patients before major surgery can help manage postoperative expectations and optimize transitions of care., (Published by Elsevier Inc.)

Purpose: Airway protective behaviors, like cough and swallow, deteriorate in many populations suffering from neurologic disorders. While coordination of these behaviors has been investigated in an animal model, it has not been tested in humans., Methods: We used a novel protocol, adapted from previous work in the cat, to assess cough and swallow independently and their coordination strategies in seven healthy males (26 ± 6 years). Surface electromyograms of the submental complex and external oblique complex, spirometry, and thoracic and abdominal wall kinematics, were used to evaluate the timing of swallow, cough, and breathing as well as lung volume (LV) during these behaviors., Results: Unlike the cat, there was significant variability in the cough-swallow phase preference; however, there was a targeted LV range in which swallow occurred., Conclusion: These results give insight into the differences between the cat and human models in airway protective strategies related to the coordination of cough and swallow behaviors, allowing for better understanding of dystussia and dysphagia.

Background: Physical inactivity impairs insulin sensitivity, which is exacerbated with aging. We examined the impact of 2 wk of acute inactivity and recovery on glycemic control, and integrated rates of muscle protein synthesis in older men and women., Methods: Twenty-two overweight, prediabetic older adults (12 men, 10 women, 69 ± 4 y) undertook 7 d of habitual activity (baseline; BL), step reduction (SR; <1,000 steps.d-1 for 14 d), followed by 14 d of recovery (RC). An oral glucose tolerance test was used to assess glycemic control and deuterated water ingestion to measure integrated rates of muscle protein synthesis., Results: Daily step count was reduced (all p < .05) from BL at SR (7362 ± 3294 to 991 ± 97) and returned to BL levels at RC (7117 ± 3819). Homeostasis model assessment-insulin resistance increased from BL to SR and Matsuda insulin sensitivity index decreased and did not return to BL in RC. Glucose and insulin area under the curve were elevated from BL to SR and did not recover in RC. Integrated muscle protein synthesis was reduced during SR and did not return to BL in RC., Conclusions: Our findings demonstrate that 2 wk of SR leads to lowered rates of muscle protein synthesis and a worsening of glycemic control that unlike younger adults is not recovered during return to normal activity in overweight, prediabetic elderly humans., Clinical Trials Registration: ClinicalTrials.gov identifier: NCT03039556.

Objective: Arteriovenous (AV) fistulas are the preferred hemodialysis access for patients with end-stage renal disease, although multiple interventions are typically needed to maintain patency. When AV fistulas thrombose, however, there is debate as to whether open thrombectomy should be attempted, particularly for salvage of upper arm fistulas. This study was designed to evaluate outcomes after open thrombectomy of upper arm and forearm AV fistulas compared with AV grafts., Methods: We identified all patients who underwent an open thrombectomy procedure for a thrombosed AV fistula or graft at a single academic medical center between January 2006 and March 2017. The specific type of AV fistula or graft was evaluated, as were the patients' demographics, comorbidities, medications, adjunctive procedures during thrombectomy, and secondary interventions. The primary outcome measures, postintervention primary patency and postintervention secondary patency, were analyzed using Kaplan-Meier curves and Cox regression models for risk adjustment., Results: During the study period, 209 open thrombectomy procedures were performed in 139 patients; 73 (35%) were undertaken in AV fistulas and 136 (65%) in grafts. Patients with upper arm fistulas (n = 52; 54% brachiocephalic, 46% brachiobasilic) and forearm fistulas (n = 16) were more likely to be male but less likely to have cerebrovascular disease or ischemic heart disease and to be receiving anticoagulation therapy compared with graft patients. After thrombectomy, the majority of patients underwent dialysis successfully (70% upper arm fistulas, 56% forearm fistulas, 63% grafts; P > .05), and 1-year survival rates were similar in all three cohorts. Postintervention primary patency at 1 year was significantly higher for AV fistulas vs grafts (33% for upper arm fistulas and 25% for forearm fistulas vs 9% for grafts; P < .05), which was confirmed in multivariate analysis, where upper arm AV fistulas had a 46% lower risk of recurrent thrombosis or secondary intervention (hazard ratio, 0.56; 95% confidence interval, 0.35-0.85; P < .05). Postintervention secondary patency at 1 year was similar between AV fistulas and grafts (44% for upper arm fistulas vs 43% for forearm fistulas vs 31% for grafts; P = .16), but in multivariate analysis, upper arm fistulas were significantly less likely to fail (hazard ratio, 0.63; 95% confidence interval, 0.40-1.00; P = .05)., Conclusions: Our data suggest that AV fistula thrombectomy is successful in up to 70% of cases, with significantly improved risk-adjusted 1-year primary and secondary patency rates for upper arm fistulas compared with grafts. Whereas the risk of access failure is high after thrombectomy, efforts to salvage upper arm AV fistulas are effective in most patients and should be undertaken when feasible., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Dysregulation of hepatic lipid and cholesterol metabolism is a significant contributor to cardiometabolic health, resulting in excessive liver lipid accumulation and ultimately non-alcoholic steatohepatitis (NASH). Therapeutic activators of the AMP-Activated Protein Kinase (AMPK) have been proposed as a treatment for metabolic diseases; we show that the AMPK β1-biased activator PF-06409577 is capable of lowering hepatic and systemic lipid and cholesterol levels in both rodent and monkey preclinical models. PF-06409577 is able to inhibit de novo lipid and cholesterol synthesis pathways, and causes a reduction in hepatic lipids and mRNA expression of markers of hepatic fibrosis. These effects require AMPK activity in the hepatocytes. Treatment of hyperlipidemic rats or cynomolgus monkeys with PF-06409577 for 6weeks resulted in a reduction in circulating cholesterol. Together these data suggest that activation of AMPK β1 complexes with PF-06409577 is capable of impacting multiple facets of liver disease and represents a promising strategy for the treatment of NAFLD and NASH in humans., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Frailty assessment can help vascular surgeons predict perioperative risk and long-term mortality for their patients. Unfortunately, comprehensive frailty assessments take too long to integrate into clinic workflow. This study was designed to evaluate 2 rapid methods for assessing frailty during vascular clinics-a short patient-reported survey and a provider-reported frailty scale., Methods: We prospectively enrolled 159 patients presenting to an academic medical center vascular surgery clinic between May and November 2016. Patients underwent frailty assessment using 2 rapid methods: (1) the Frail Nondisabled (FiND) survey (5 questions) and (2) the Clinical Frailty Scale (CFS; 9-point scale from robust to severely frail). These were followed by administering the Fried Index, a validated frailty assessment method with 5 measures (weight loss, exhaustion, grip strength, walking speed, and activity level). The correlation between Fried scores (reference standard) with frailty diagnoses derived from FiND and CFS was analyzed using the Spearman-rank test, Cohen's kappa, sensitivity/specificity tests, and receiver operating curves., Results: The evaluated cohort included 87 (55%) females, a mean age of 61 years, 126 (79%) preoperative patients, and 32 (20%) categorized as frail using the Fried Index criteria. The FiND survey was very sensitive (91%) but less specific for diagnosing frailty. In comparison, the CFS was highly specific (96%) for diagnosing frailty and exhibited high inter-rater reliability between surgeon and medical assistant scores (kappa: 0.79; 95% CI: 0.72-0.87; P < 0.001). There was moderate correlation between frailty assigned using the Fried Index and the CFS (rho: 0.41-0.44)., Conclusions: Frailty can be quickly and effectively assessed during vascular surgery clinic using a combination of patient-reported (FiND) and provider-reported (CFS) methods to improve diagnostic accuracy. Implementing routine frailty assessment into clinic workflow can be a valuable tool for risk prediction and surgical decision-making., (Published by Elsevier Inc.)