Telecommuting and Travel during COVID-19: An Exploratory Analysis across Different Population Geographies in the U.S.A.

This study explores the impact of the COVID-19 pandemic on telecommuting (working from home) and travel during the first year of the pandemic in the U.S.A. (from March 2020 to March 2021), with a particular focus on examining the variation in impact across different U.S. geographies. We divided 50 U.S. states into several clusters based on their geographic and telecommuting characteristics. Using K-means clustering, we identified four clusters comprising 6 small urban states, 8 large urban states, 18 urban-rural mixed states, and 17 rural states. Combining data from multiple sources, we observed that nearly one-third of the U.S. workforce worked from home during the pandemic, which was six times higher than the pre-pandemic period, and that these fractions varied across the clusters. More people worked from home in urban states compared with rural states. As well as telecommuting, we examined several activity travel trends across these clusters: reduction in the number of activity visits; changes in the number of trips and vehicle-miles traveled; and mode usage. Our analysis showed there was a greater reduction in the number of workplace and nonworkplace visits in urban states compared with rural states. The number of trips in all distance categories decreased except for long-distance trips, which increased during the summer and fall of 2020. The changes in overall mode usage frequency were similar across urban and rural states with a large drop in ride-hailing and transit use. This comprehensive study can provide a better understanding of the regional variation in the impact of the pandemic on telecommuting and travel, which can facilitate informed decision-making.

Impact of working from home on activity-travel behavior during the COVID-19 Pandemic: An aggregate structural analysis.

The ongoing COVID-19 pandemic has created significant public health concerns that led the public and private sectors to impose stay-at-home and work-from-home policies. Although working from home has been a conventional albeit infrequent behavior, the prevalence of this option was significantly and rapidly accelerated during the pandemic. This study explored the impacts of working from home on activity-travel behavior during the pandemic. Both work and non-work activity participation declined during the pandemic but to what extent was this due to working from home? How did working from home affect other measures of travel such as person-miles traveled? We approached these questions by developing a Structural Regression model and using cross-sectional data for the early phase of the pandemic when the infection curve was flattened and activity-travel behavior became relatively stable following the drastic changes observed during the pandemic's initial shock. Combining U.S. county-level data from the Maryland Transportation Institute and Google Mobility Reports, we concluded that the proportion of people working from home directly depended on pandemic severity and associated public health policies as well as on a range of socio-economic characteristics. Working from home contributed to a reduction in workplace visits. It also reduced non-work activities but only via a reduction in non-work activities linked to work. Finally, a higher working from home proportion in a county corresponded to a reduction in average person-miles traveled. A higher degree of state government responses to containment and closure policies contributed to an increase in working from home, and decreases in workplace and non-workplace visits and person-miles traveled in a county. The results of this study provide important insights into changes in activity-travel behavior associated with working from home as a response strategy to major disruptions such as those imposed by a pandemic.

Endotension: What do we know and not know about this enigmatic complication of endovascular aneurysm repair.

As the use of endovascular approaches to treat aneurysm repair continues to increase, more and more patients have been identified with endoleaks. Five types of endoleaks have been defined. Endotension, or type V endoleak, remains controversial owing to its variable definition across studies and the range of proposed treatments. Thus, we performed a review of the reported studies to summarize the diagnosis and treatment of this rare complication after endovascular aneurysm repair to determine what we do and do not know about this rare form of endoleak. The presence of an endoleak places patients at an increased risk of aneurysm sac enlargement and potential rupture. Although additional research is essential and yet difficult to perform, we sought to provide a guide for the management of this perplexing endoleak known as endotension.

Double Mandibular Osteotomy for Access to High-Carotid Pathology.

BACKGROUND: Anecdotal experience demonstrates the existence of patients with superiorly located carotid stenosis, neoplasms, or aneurysms where the mandible obstructs effective surgical access using standard techniques. As carotid pathology extends anatomically beyond the limits of standard operative technique, additional exposure becomes paramount to safely and effectively address the lesion. Double mandibular osteotomy (DMO) is one of several techniques to obtain additional exposure to high-carotid pathology; however, there is no large series to address the outcomes of patients undergoing this procedure. METHODS: A retrospective case series was performed for all patients undergoing surgery for carotid pathology from 2011-2019 that could not be approached with standard cervical incision. The primary predictor variable was high-anatomic carotid pathology necessitating DMO. The primary outcome variable was early and late complications sustained by patients. RESULTS: Fifteen patients met study criteria and underwent 16 DMOs to access high-carotid pathology including carotid stenosis (n = 8 patients), carotid aneurysm (n = 2 patients), and carotid body tumor (n = 8 patients). Two patients had dual ipsilateral pathology with one patient having both carotid artery stenosis and aneurysm, and the other patient diagnosed with carotid artery stenosis and carotid body tumor. One patient had bilateral carotid artery stenosis, each requiring high anatomic exposure for treatment. Early complications occurred in 8 patients. Five patients experienced significant dysphagia requiring enteral feeding, and 2 patients developed malocclusion directly related to the double mandibular osteotomy. One patient experienced contralateral cortical watershed infarcts. Late complications included one patient developing osteomyelitis of the mandible, and this patient also developed distal mandibular segment screw exposure. The comparison of the outcome groups for categorical predictor variables using Fisher's exact test detected no statistically significant differences for gender, hypertension, hyperlipidemia, type 2 diabetes, chronic obstructive pulmonary disease, tobacco use, chronic kidney disease, or cerebrovascular disease. For the continuous variable comparisons, independent-samples t-tests detected no difference between the complication groups for age, operative time, or years of follow-up. No significant differences were found between the groups for body mass index or intraoperative blood loss. CONCLUSIONS: The double mandibular osteotomy provides excellent exposure and surgical access to the distal internal carotid artery for repair of vascular pathology with acceptable outcomes and long-term complications compared with previously reported techniques. Because of the early complications realized with the DMO, we recommend the procedure for symptomatic patients with a high risk of failing medical therapy alone and not appropriate for endovascular treatment as well as those patients with tumors requiring surgical intervention.

Ostomy Usage for Colorectal Trauma in Combat Casualties.

INTRODUCTION: The role for diverting ostomy as a method to help reduce morbidity and mortality has been well established in the combat trauma population. However, factors that influence the type of ostomy used and which ostomies become permanent are poorly studied. We examine patterns of ostomy usage and reversal in a large series of combat trauma patients. METHODS: We performed a retrospective review of combat casualties treated at our continental U.S. military treatment facility from 2003 to 2015. All patients who underwent ostomy formation were included. Clinical and demographic factors were collected for all patients including the type of ostomy and whether or not ostomy reversal took place. Patients were grouped and analyzed based on ostomy type and by ostomy reversal. RESULTS: We identified 202 patients who had ostomies created. End colostomies were most common (N = 149) followed by loop colostomies (N = 34) and end ileostomies (N = 19). Casualties that underwent damage control laparotomy (DCL) were less likely to have a loop colostomy created (p < 0.001). Ostomy reversal occurred in 89.9% of patients. There was no difference in ostomy reversal rates by ostomy type (p = 0.080). Presence of a pelvic fracture was associated with permanent ostomy (OR = 3.28, p = 0.019), but no factor independently predicted a permanent ostomy on multivariate analysis. DISCUSSION: DCL and a severe perineal injury most strongly influence ostomy type selection. Most patients undergo colostomy reversal, and no factor independently predicted an ostomy being permanent. These findings provide a framework for understanding the issue of fecal diversion in the combat trauma population and inform military surgeons about injury patterns and treatment options.

The Efficacy of Systemic Doxycycline Administration as an Inhibitor of Intimal Hyperplasia after Balloon Angioplasty Arterial Injury.

BACKGROUND: Intimal hyperplasia (IH) is the most common indicator for secondary intervention in peripheral vascular disease. Matrix metalloproteinases (MMPs) play a role in IH development due to their degradation of the extracellular matrix. Doxycycline (Doxy), a member of the tetracycline family of antibiotics, is a potent MMP inhibitor. We have previously shown that Doxy inhibits MMP activity and vascular smooth muscle cell migration in vitro. We hypothesized that Doxy would decrease MMP activity in vivo and inhibit the development of IH in a rodent model of vascular injury. METHODS AND RESULTS: Doxy (400 mg/pellet) was delivered by a slow-release pellet implanted 3 days prior to or at the time of balloon angioplasty (BA) of the common carotid artery in female rats. At 14 days post-BA, intima-to-media (I:M) ratios were 0.77 ± 0.21 and 1.04 ± 0.32 in the Doxy treated groups, respectively, compared to 1.25 ± 0.26 in the control group (P = not significant; n = 3). Additionally, the tested dose of Doxy in either group had no inhibitory effect on membrane type 1-MMP or MMP-2 tissue levels, as measured by immunohistochemistry, or on systemic levels of MMP, as measured by total MMP serum levels using enzyme-linked immunosorbent assay. At 14 days post-BA, VSMC proliferation in the injured artery was increased to Doxy treatment prior to and at the time of surgery (23.5 ± 3.4 and 27.2 ± 3.9%, respectively), compared to control (11.4 ± 0.4%; n = 3), as measured by proliferating cellular nuclear antigen immunostaining. CONCLUSIONS: In our in vivo model of vascular injury, systemic Doxy administration prior to or at the time of vascular injury does not significantly hinder the progression of IH development. Additional doses and routes of administration could be examined in order to correlate therapeutic serum levels of Doxy with effective MMP inhibition in serum and arterial tissue. However, alternative drug delivery systems are needed in order to optimize therapeutic administration of targeted MMP inhibitors for the prevention of IH development.

Laparoscopy for Colon Cancer.

The use of laparoscopy has become widespread across many surgical specialties. Its utility as treatment for colon cancer was initially met with hesitancy due to concern for port site and wound recurrences; however, this was later disproven by large retrospective series. Subsequently, there have been multiple, large, prospective, randomized studies evaluating laparoscopic versus open colectomy for colon cancer. All studies yielded similar results and showed no statistical difference in overall survival, disease-free survival, and recurrence. Additionally, these studies revealed similar operative outcomes with respect to complication rates, perioperative mortality, and conversion to open colectomy, as well as equivalent oncologic resections. Overall in the laparoscopic colectomy groups, hospital stays were shorter, and often times patients required less narcotics postoperatively, but laparoscopic operative times were longer. With adequate training, the use of laparoscopy can be safely employed for patients with colon cancer.

Three-dimensional fusion computed tomography decreases radiation exposure, procedure time, and contrast use during fenestrated endovascular aortic repair.

OBJECTIVE: Endovascular surgery has revolutionized the treatment of aortic aneurysms; however, these improvements have come at the cost of increased radiation and contrast exposure, particularly for more complex procedures. Three-dimensional (3D) fusion computed tomography (CT) imaging is a new technology that may facilitate these repairs. The purpose of this analysis was to determine the effect of using intraoperative 3D fusion CT on the performance of fenestrated endovascular aortic repair (FEVAR). METHODS: Our institutional database was reviewed to identify patients undergoing branched or FEVAR. Patients treated using 3D fusion CT were compared with patients treated in the immediate 12-month period before implementation of this technology when procedures were performed in a standard hybrid operating room without CT fusion capabilities. Primary end points included patient radiation exposure (cumulated air kerma: mGy), fluoroscopy time (minutes), contrast usage (mL), and procedure time (minutes). Patients were grouped by the number of aortic graft fenestrations revascularized with a stent graft, and operative outcomes were compared. RESULTS: A total of 72 patients (41 before vs 31 after 3D fusion CT implementation) underwent FEVAR from September 2012 through March 2014. For two-vessel fenestrated endografts, there was a significant decrease in radiation exposure (3400 ± 1900 vs 1380 ± 520 mGy; P = .001), fluoroscopy time (63 ± 29 vs 41 ± 11 minutes; P = .02), and contrast usage (69 ± 16 vs 26 ± 8 mL; P = .0002) with intraoperative 3D fusion CT. Similarly, for combined three-vessel and four-vessel FEVAR, significantly decreased radiation exposure (5400 ± 2225 vs 2700 ± 1400 mGy; P < .0001), fluoroscopy time (89 ± 36 vs 64 ± 21 minutes; P = .02), contrast usage (90 ± 25 vs 39 ± 17 mL; P < .0001), and procedure time (330 ± 100 vs 230 ± 50 minutes; P = .002) was noted. Estimated blood loss was significantly less (P < .0001), and length of stay had a trend (P = .07) toward being lower for all patients in the 3D fusion CT group. CONCLUSIONS: These results demonstrate that use of intraoperative 3D fusion CT imaging during FEVAR can significantly decrease radiation exposure, procedure time, and contrast usage, which may also decrease the overall physiologic impact of the repair.

Stride Leg Ground Reaction Forces Predict Throwing Velocity in Adult Recreational Baseball Pitchers.

Ground reaction forces produced during baseball pitching have a significant impact in the development of ball velocity. However, the measurement of only one leg and small sample sizes in these studies curb the understanding of ground reaction forces as they relate to pitching. This study aimed to further clarify the role ground reaction forces play in developing pitching velocity. Eighteen former competitive baseball players with previous high school or collegiate pitching experience threw 15 fastballs from a pitcher's mound instrumented to measure ground reaction forces under both the drive and stride legs. Peak ground reaction forces were recorded during each phase of the pitching cycle, between peak knee height and ball release, in the medial/lateral, anterior/posterior, and vertical directions, and the peak resultant ground reaction force. Stride leg ground reaction forces during the arm-cocking and arm-acceleration phases were strongly correlated with ball velocity (r2 = 0.45-0.61), whereas drive leg ground reaction forces showed no significant correlations. Stepwise linear regression analysis found that peak stride leg ground reaction force during the arm-cocking phase was the best predictor of ball velocity (r2 = 0.61) among drive and stride leg ground reaction forces. This study demonstrates the importance of ground reaction force development in pitching, with stride leg forces being strongly predictive of ball velocity. Further research is needed to further clarify the role of ground reaction forces in pitching and to develop training programs designed to improve upper extremity mechanics and pitching performance through effective force development.

Reliability of 3-Dimensional Measures of Single-Leg Drop Landing Across 3 Institutions: Implications for Multicenter Research for Secondary ACL-Injury Prevention.

CONTEXT: Due to the limitations of single-center studies in achieving appropriate sampling with relatively rare disorders, multicenter collaborations have been proposed to achieve desired sampling levels. However, documented reliability of biomechanical data is necessary for multicenter injury-prevention studies and is currently unavailable. OBJECTIVE: To measure the reliability of 3-dimensional (3D) biomechanical waveforms from kinetic and kinematic variables during a single-leg landing (SLL) performed at 3 separate testing facilities. DESIGN: Multicenter reliability study. SETTING: 3 laboratories. PATIENTS: 25 female junior varsity and varsity high school volleyball players who visited each facility over a 1-mo period. INTERVENTION: Subjects were instrumented with 43 reflective markers to record 3D motion as they performed SLLs. During the SLL the athlete balanced on 1 leg, dropped down off of a 31-cm-high box, and landed on the same leg. Kinematic and kinetic data from both legs were processed from 2 trials across the 3 laboratories. MAIN OUTCOME MEASURES: Coefficients of multiple correlations (CMC) were used to statistically compare each joint angle and moment waveform for the first 500 ms of landing. RESULTS: Average CMC for lower-extremity sagittal-plane motion was excellent between laboratories (hip .98, knee .95, ankle .99). Average CMC for lower-extremity frontal-plane motion was also excellent between laboratories (hip .98, knee .80, ankle .93). Kinetic waveforms were repeatable in each plane of rotation (3-center mean CMC ≥.71), while knee sagittal-plane moments were the most consistent measure across sites (3-center mean CMC ≥.94). CONCLUSIONS: CMC waveform comparisons were similar relative to the joint measured to previously published reports of between-sessions reliability of sagittal- and frontal-plane biomechanics performed at a single institution. Continued research is needed to further standardize technology and methods to help ensure that highly reliable results can be achieved with multicenter biomechanical screening models.

Elective endovascular aortic repair conversion for type Ia endoleak is not associated with increased morbidity or mortality compared with primary juxtarenal aneurysm repair.

OBJECTIVE: Type Ia endoleak after endovascular aortic repair (EVAR) can be a challenging complication to manage, and due to concerns regarding morbidity and mortality of open surgical conversion (OSC), reports of complex endoluminal salvage techniques are increasing. Despite development of these endovascular remedial strategies, many patients ultimately require OSC. The purpose of this analysis was to outcomes of elective OSC for type Ia endoleak and compare them with elective primary open juxtarenal aneurysm repair (OJAR) to determine if these concerns are warranted. METHODS: From 2000 to 2012, 54 patients underwent EVAR OSC at median time of 27 months (interquartile range, 9-55 months). Indications included endograft thrombosis in 2 (4%), intraoperative EVAR failure in 3 (6%), rupture in 5 (9%), graft infection in 6 (11%), and type Ia endoleak in 25 (all: 38 [70%]). Because many OSCs are performed for emergency indications without endovascular options, we chose elective type Ia endoleak patients as our study group. These 25 patients were compared with an elective OJAR cohort matched by anatomy and comorbidities. Primary end points were 30-day and 1-year mortality. Secondary end points included early complications, cross-clamp time, procedure time, blood loss, and length of stay. RESULTS: Demographic and comorbidity data in the OSC and OJAR groups did not differ, with the exception that OJAR patients presented with smaller aneurysm diameter and a higher rate of chronic obstructive pulmonary disease (P = .03). OSC patients more frequently underwent a nontube graft repair (OSC, n = 20 [80%] vs OJAR, n = 6 [24%]; P = .0002), required longer procedure times (P = .03), and received more plasma transfusions (P = .03). The 30-day mortality was 4% in both groups (observed difference in rates, 0%; 95% confidence interval for difference in mortality rates, -14.0% to 14.0%; P = 1). A similar rate of major complications occurred (OSC, n = 9 [36%] vs OJAR, n = 8 [32%]; P = 1). One-year survival was 83% in OSC and 91% in OJAR (observed difference, 7%; 95% confidence interval, -15% to 29%; P = .65). CONCLUSIONS: Despite many advances in EVAR technology, the need for OSC persists and will likely become more common as older-generation devices fail or providers attempt EVAR in more anatomically complex patients. Elective OSC for type Ia endoleak can be technically challenging but is not associated with increased morbidity or mortality compared with OJAR in appropriately selected patients. These results should be considered before pursuing complex endovascular remediation of EVAR failures.

Hip adductor activations during run-to-cut manoeuvres in compression shorts: implications for return to sport after groin injury.

Athletes at high risk of groin strains in sports such as hockey and soccer often choose to wear shorts with directional compression to aid in prevention of or recovery from hip adductor strains. Large, eccentric contractions are known to result in or exacerbate strain injuries, but it is unknown if these shorts have a beneficial effect on hip adductor muscle activity. In this study, surface electromyography (EMG) of the adductor longus and ground reaction force (GRF) data were obtained simultaneously on 29 healthy individuals without previous history of serious injury while performing unanticipated 45° run-to-cut manoeuvres in a laboratory setting wearing shorts with non-directional compression (control, HeatGear, Under Armour, USA) or shorts with directional compression (directional, CoreShort PRO, Under Armour, USA), in random order. Average adductor activity in the stance leg was significantly lower in the directional condition than in the control condition during all parts of stance phase (all P < 0.042). From this preliminary analysis, wearing directional compression shorts appears to be associated with reduced stance limb hip adductor activity. Athletes seeking to reduce demand on the hip adductors as they approach full return to activities may benefit from the use of directional compression shorts.

Controversies surrounding quality measurement in colon and rectal surgery.

Quality improvement in health care has become a major topic of discussion among health care providers, patients, insurance companies, and the government. National Surgical Quality Improvement Project (NSQIP), along with a multitude of other programs, exists in an attempt to create objective data that can be used to compare hospitals and providers against a national average. Studies have shown that despite good patient care and proper surgical technique, patients who undergo procedures such as colectomy have a higher incidence of surgical site infection (SSI) and other morbidities. Therefore, hospitals with a large volume of colon and rectal surgery cases are routinely identified as "high outliers" in these quality improvement programs. Programs, such as NSQIP, may not be the best way to measure quality in specific subspecialties such as colon and rectal surgery.

Predictions of total work based on measures of muscle strength and hop performance in individuals after ACL reconstruction.

OBJECTIVES: The purpose of this study was to determine the ability to utilize clinical measures of hop performance and thigh muscle strength to predict total limb work, a measure of cumulative single leg power, in young athletes at the time of return to sport after ACLR. We hypothesized that hop test performance and thigh muscle strength would predict total limb work during a maximal effort repeated vertical single-leg jump and that hop test performance would better predict total limb work during a maximal effort repeated vertical single-leg jump than measures of thigh strength. DESIGN: Cross-sectional study. PARTICIPANTS: Analysis on data from 50 individuals after unilateral ACLR (74% women, age 14-23 years) MAIN OUTCOME MEASURES: Performed 10-s repeated vertical single-leg jump test on a force platform where single limb power and resultant total work were calculated. At the same session, participants completed a clinical single leg hop test battery and thigh strength testing. RESULTS: All clinical measures were associated with total work during the repeated vertical single-leg jump test on the involved and uninvolved limbs, respectfully. After controlling for height and weight, quadriceps femoris peak torque at 180°/s was the strongest predictor of total work for both limbs. On the involved limb, performance on the triple hop test for distance also uniquely contributed to the prediction of total work. CONCLUSIONS: Quadriceps femoris muscle strength and distance hop test performance predict total limb work capacity of the involved limb during a single-leg dynamic task. Optimizing both measures after ACLR may positively impact vital components of sports performance.

Visual cognition associated with knee proprioception, time to stability, and sensory integration neural activity after ACL reconstruction.

Visual cognitive ability has previously been associated with anterior cruciate ligament injury and injury risk biomechanics in healthy athletes. Neuroimaging reports have identified increased neural activity in regions corresponding to visual-spatial processing, sensory integration, and visual cognition in individuals after anterior cruciate ligament reconstruction (ACLR), indicating potential neural compensatory strategies for motor control. However, it remains unclear whether there is a relationship between visual cognition, neural activity, and metrics of neuromuscular ability after ACLR. The purpose of this study was to (1) evaluate the relationship between visual cognitive function and measurements of neuromuscular control (proprioception and time to stability [TTS]), isokinetic strength, and subjective function, and (2) examine the neural correlates of visual cognition between ACLR (n = 16; time since surgery 41.4 ± 33.0 months) and demographically similar controls (n = 15). Visual cognition was assessed by the ImPACT visual motor and visual memory subscales. Outcome variables of proprioception to target knee angle 20°, landing TTS, strength, and subjective function were compared between groups, and visual cognition was correlated within groups to determine the relationship between visual cognition and outcome variables controlled for time from surgery (ACLR group). The control group had better IKDC scores and strength. Visual memory and visual motor ability were negatively associated with proprioception error (r = -0.63) and TTS (r = -0.61), respectively, in the ACLR group but not controls. Visual cognition was associated with increased neural activity in the precuneus and posterior cingulate cortex in the ACLR group but not control participants. These data suggest the neural strategy in which ACLR participants maintain proprioception and stability varies, and may depend on visual cognition and sensory integration neural activity.

Ipsilateral motor cortical responses to TMS during lengthening and shortening of the contralateral wrist flexors.

Unilateral lengthening contractions provide a greater stimulus for neuromuscular adaptation than shortening contractions in the active and non-active contralateral homologous muscle, although little is known of the potential mechanism. Here we examined the possibility that corticospinal and spinal excitability vary in a contraction-specific manner in the relaxed right flexor carpi radialis (FCR) when humans perform unilateral lengthening and shortening contractions of the left wrist flexors at the same absolute force. Corticospinal excitability in the relaxed right FCR increased more during lengthening than shortening at 80% and 100% of maximum voluntary contraction (MVC). Short-interval intracortical inhibition diminished during shortening contractions, and it became nearly abolished during lengthening. Intracortical facilitation lessened during shortening but increased during lengthening. Interhemispheric inhibition to the 'non-active' motor cortex diminished during shortening, and became nearly abolished during lengthening at 90% MVC. The amplitude of the Hoffman reflex in the relaxed right FCR decreased during and remained depressed for 20 s after lengthening and shortening of the left wrist flexors. We discuss the possibility that instead of the increased afferent input, differences in the descending motor command and activation of brain areas that link function of the motor cortices during muscle lengthening vs. shortening may cause the contraction-specific modulation of ipsilateral motor cortical output. In conclusion, ipsilateral motor cortex responses to transcranial magnetic stimulation are contraction-specific; unilateral lengthening and shortening contractions reduced contralateral spinal excitability, but uniquely modulated ipsilateral corticospinal excitability and the networks involved in intracortical and interhemispheric connections, which may have clinical implications.

Continuing Medical Education and Lifelong Learning.

Continuing medical education is an ongoing process to educate clinicians and provide patients with up-to-date, evidence-based care. Since its inception, the maintenance of certification (MOC) program has changed dramatically. This article reviews the development of MOC and its integration with the 6 core competencies, including the practice-based learning and improvement cycle. The concept of lifelong learning is discussed, with specific focus on different methods for surgeons to engage in learning, including simulation, coaching, and communities of practice. In addition, the future of MOC in continuous professional development is reviewed.

Advances in the Formulation and Assembly of Non-Cationic Lipid Nanoparticles for the Medical Application of Gene Therapeutics.

Lipid nanoparticles have become increasingly popular delivery platforms in the field of gene therapy, but bench-to-bedside success has been limited. Many liposomal gene vectors are comprised of synthetic cationic lipids, which are associated with lipid-induced cytotoxicity and immunogenicity. Natural, non-cationic PEGylated liposomes (PLPs) demonstrate favorable biocompatibility profiles but are not considered viable gene delivery vehicles due to inefficient nucleic acid loading and reduced cellular uptake. PLPs can be modified with cell-penetrating peptides (CPPs) to enhance the intracellular delivery of liposomal cargo but encapsulate leakage upon CPP-PLP assembly is problematic. Here, we aimed to identify parameters that overcome these performance barriers by incorporating nucleic acid condensers during CPP-PLP assembly and screening variable ethanol injection parameters for optimization. CPP-PLPs were formed with R8-amphiphiles via pre-insertion, post-insertion and post-conjugation techniques and liposomes were characterized for size, surface charge, homogeneity, siRNA encapsulation efficiency and retention and cell associative properties. Herein we demonstrate that pre-insertion of stearylated R8 into PLPs is an efficient method to produce non-cationic CPP-PLPs and we provide additional assembly parameter specifications for a modified ethanol injection technique that is optimized for siRNA encapsulation/retention and enhanced cell association. This assembly technique could provide improved clinical translation of liposomal based gene therapy applications.

Liposomal Nanocarriers Designed for Sub-Endothelial Matrix Targeting under Vascular Flow Conditions.

Vascular interventions result in the disruption of the tunica intima and the exposure of sub-endothelial matrix proteins. Nanoparticles designed to bind to these exposed matrices could provide targeted drug delivery systems aimed at inhibiting dysfunctional vascular remodeling and improving intervention outcomes. Here, we present the progress in the development of targeted liposomal nanocarriers designed for preferential collagen IV binding under simulated static vascular flow conditions. PEGylated liposomes (PLPs), previously established as effective delivery systems in vascular cells types, served as non-targeting controls. Collagen-targeting liposomes (CT-PLPs) were formed by conjugating established collagen-binding peptides to modified lipid heads via click chemistry (CTL), and inserting them at varying mol% either at the time of PLP assembly or via micellar transfer. All groups included fluorescently labeled lipid species for imaging and quantification. Liposomes were exposed to collagen IV matrices statically or via hemodynamic flow, and binding was measured via fluorometric analyses. CT-PLPs formed with 5 mol% CTL at the time of assembly demonstrated the highest binding affinity to collagen IV under static conditions, while maintaining a nanoparticle characterization profile of ~50 nm size and a homogeneity polydispersity index (PDI) of ~0.2 favorable for clinical translation. When liposomes were exposed to collagen matrices within a pressurized flow system, empirically defined CT-PLPs demonstrated significant binding at shear stresses mimetic of physiological through pathological conditions in both the venous and arterial architectures. Furthermore, when human saphenous vein explants were perfused with liposomes within a closed bioreactor system, CT-PLPs demonstrated significant ex vivo binding to diseased vascular tissue. Ongoing studies aim to further develop CT-PLPs for controlled targeting in a rodent model of vascular injury. The CT-PLP nanocarriers established here show promise as the framework for a spatially controlled delivery platform for future application in targeted vascular therapeutics.