Optimizing the diagnostic approach of functional popliteal artery entrapment syndrome.

OBJECTIVE: Functional popliteal artery entrapment syndrome (fPAES) is an underdiagnosed and undertreated etiology of atypical claudication. Symptoms of fPAES include deep posterior muscle cramping and pain with exercise and, unlike anatomic PAES, there are seldom vascular complications. Common noninvasive diagnostic modalities include ankle-brachial index, arterial duplex Doppler ultrasound (DUS) examination, and cross-sectional imaging such as magnetic resonance angiography (MRA). Entrapment can be difficult to reproduce during diagnostic testing, requiring provocative maneuvers. Because we believed different provocative maneuvers provide different diagnostic efficacy, we sought to optimize our diagnostic approach to fPAES. METHODS: We performed a retrospective review of patients before and after optimizing our noninvasive imaging protocol comparing patients with fPAES versus other atypical claudicants with chronic compartment syndrome. RESULTS: Arterial DUS examination and exercise ankle-brachial index were important components of our protocol with a significant decrease in systolic posterior tibial blood pressure of -14 mm Hg after exercise, whereas nonentrapment release patients had an overall increase of 8 mm Hg (P = .006). Arterial DUS examination of the distal PA with forced plantarflexion demonstrated a trend toward an increase in the measured velocity ratio, especially in the middle and distal PA. MRA with stressed plantar flexion findings were positive in 6 of 11 patients with fPAES, with false negatives likely owing to patients' inability to maintain a provocative position for the duration of the MRA. CONCLUSIONS: Diagnosing fPAES is challenging owing to a lack of standardized diagnostic testing and provocative maneuvers. Different maneuvers demonstrated varying diagnostic yields for fPAES. Exercise ABIs were the most reliable vascular laboratory test to detect changes attributable to fPAES and to distinguish it from chronic compartment syndrome. Segmental PA DUS examination seems to be promising as a means of detecting PA impingement. Stress positional MRA effectively demonstrates anatomic PAES, but has a false-negative rate for fPAES.

Direct oral anticoagulants decrease treatment failure for acute lower extremity deep venous thrombosis.

OBJECTIVE: Optimal medical therapy for acute lower extremity deep venous thrombosis (DVT) remains an enigma. While clinical trials demonstrate non-inferiority with an oral anti-Xa inhibitor, or direct oral anticoagulant (DOAC), versus combined low-molecular weight heparin (LMWH) and oral vitamin K antagonist (VKA), the most effective regimen remains to be determined. METHODS: This study is a single-center retrospective cohort study from October 2014 to December 2015 of patients with a diagnosis of acute DVT and subsequent serial lower extremity venous duplex. Demographics, medical history, medications, serial ultrasound findings, as well as the primary anticoagulant used for treatment were collected and analyzed by two independent data extractors. Treatment failure was defined as any new DVT or progression of an existing DVT within 3 months of diagnosis of the index clot. Risk factors for treatment failure were assessed using standard odds ratios and Fischer's exact test. RESULTS: Among 496 patients with an acute lower extremity DVT, 54% (n = 266) were men, mean age was 61 years, 35% (n = 174) involved the popliteal or more proximal segments, and 442 had documentation of the primary treatment for DVT: 20% (n = 90) received nothing; 20% (n = 92) received an oral VKA; 34% (n = 149) received a DOAC; 20% (n = 90) received LMWH; and 5% (n = 21) received another class of anticoagulant. Within 3 months, 21% (n=89 out of 427) had treatment failure defined as any new DVT or progression of prior DVT. Patients treated with a DOAC were less likely to experience treatment failure when compared with any other treatment (odds ratio 0.43; 95% confidence intervals [0.23, 0.79]; p = 0.0069) and when compared with traditional oral VKA (OR 0.44; 95% CI [0.21, 0.92]; p = 0.029). None of prior history of DVT, pulmonary embolism, thrombophilia, renal insufficiency, hepatic insufficiency, cancer, or antiplatelet therapy correlated with treatment failure. Treatment outcome did not correlate with being on any anticoagulation versus none (p = 0.74), nor did it correlate with the duration of treatment (<3 months versus ≥3 months) (p = 0.42). Proximal and distal DVTs showed no difference in treatment failure (19% versus 22%, respectively; p = 0.43). CONCLUSION: In summary, the use of a DOAC for acute lower extremity DVT yielded better overall outcomes and fewer treatment failures at 3 months as compared to traditional oral VKA therapy based on serial duplex imaging.

Endoluminal Atherosclerotic Plaque Debulking Using Enzymatic and Ultrasonic Energy.

BACKGROUND: Current procedures to treat severe atherosclerosis are traumatic to the arterial wall and often result in restenosis due to neointimal hyperplasia. We developed a novel therapy using a specially designed double occlusion balloon catheter, ultrasonic wire, and enzymatic digestion solution to atraumatically debulk atherosclerotic plaques. MATERIALS AND METHODS: A combination of different enzymes, chemicals, and treatment conditions were evaluated for its effect at reducing atherosclerotic plaque harvested from human carotid artery endarterectomies ex vivo. The optimized digestion solution was examined in harvested intact human superficial femoral arteries in situ. A conventional Yorkshire/Landrace and a genetically modified Yucatan minipig homozygous for a nonfunctional LDLR mutation were used to evaluate the endovascular therapy in nonatherosclerotic and atherosclerotic environments in vivo. RESULTS: Ex vivo, the technology successfully digested human carotid artery plaques by 75%. In situ, the therapy successfully reduced plaque area in harvested superficial femoral arteries by 46%. In vivo, the endovascular therapy was technically feasible and demonstrated initial safety with no thrombosis, dissection, or aneurysmal dilatation in a nonatherosclerotic porcine model. In an atherosclerotic porcine model, the therapy demonstrated initial efficacy by successfully reducing atherosclerotic plaque while preserving the arterial wall with an intact internal elastic lamina. CONCLUSIONS: Using human plaque, human artery, and a normal and atherosclerotic pig model, we demonstrated that delivery of our therapy to the vasculature is technically feasible, appears safe, and shows initial efficacy. Our percutaneous plaque debulking method is a unique and promising therapy for the treatment of atherosclerosis and warrants further study.

Ten-year review of isolated spontaneous mesenteric arterial dissections.

OBJECTIVE: Isolated spontaneous dissection of the superior mesenteric artery (SMA) and celiac artery (CA) remains a rare condition; however, it has been increasingly noted incidentally on diagnostic imaging. The purpose of this study was to examine the natural history and outcomes of patients presenting with isolated spontaneous mesenteric artery dissection (SMAD). We hypothesized that most SMADs can be treated nonoperatively. METHODS: This was a single-center retrospective review of patients presenting with the diagnosis of SMAD between 2006 and 2016. Data analysis included demographics, clinical data, radiologic review, treatment, and outcomes. RESULTS: A total of 77 patients were found to have CA dissection, SMA dissection, or both in the absence of aortic dissection diagnosed on computed tomography or magnetic resonance imaging. The average age was 56 years (range, 26-86 years), 80% were male, and 10 patients (13%) had underlying connective tissue disorders. The majority, 64%, presented with symptoms including abdominal pain, back pain, and chest pain; the remaining 36% were asymptomatic. Combined SMA and CA dissection was found in 14 (18%) patients; 33 (43%) presented with isolated CA dissection, and 30 (39%) presented with isolated SMA dissection. Only four patients required intervention. Mesenteric bypass was performed in two patients, and SMA endarterectomy with patch angioplasty was performed in one patient for signs of bowel ischemia. No patient required bowel resection. The two bypasses were anastomosed to a branch of the SMA, and complete lumen restoration was seen on long-term imaging follow-up. One patient underwent stent grafting of the CA and hepatic artery for aneurysmal degeneration 1 month after diagnosis. The remaining 73 patients were managed nonoperatively; 40 (52%) were treated with a short course of anticoagulation, 23 (30%) were treated with antiplatelet therapy, and 10 (13%) were treated with observation alone. No other late interventions or recurrences were noted during a mean follow-up of 21 months. CONCLUSIONS: Whereas isolated SMAD poses a risk of visceral ischemia, most patients presenting with this diagnosis can be treated nonoperatively with a short course of antiplatelet or anticoagulant therapy. Only a small number of patients require surgical revascularization for bowel ischemia.

Targeted Nanotherapies for the Treatment of Surgical Diseases.

OBJECTIVE: To describe the components of targeted nanotherapeutics and to review their applications in the treatment of surgical diseases. BACKGROUND: Targeted nanotherapeutic is a novel strategy for treating a variety of diseases and is an emerging technology that offers advantages over current treatment strategies. The nanoscale size, combined with the ability to surface functionalize the delivery vehicle to enable targeting and incorporate a therapeutic payload, provides a new and innovative therapeutic platform to treat surgical diseases that has yet to be fully realized in the surgical arena. METHODS: A comprehensive literature review of nanotherapeutics, targeting strategies, and their utility in treating surgical diseases is performed. RESULTS: Targeted nanotherapeutics have demonstrated safety and biocompatibility in treating surgical diseases. The ability to surface functionalize the nanoparticles affords a unique tailorability that enables targeting specificity and therapeutic payload delivery to treat a variety of surgical diseases. Moreover, the small size and targeting capabilities allow access to biological compartments, such as the blood-brain barrier, that have previously been difficult to treat. CONCLUSIONS: Targeted nanotherapeutics represent a novel therapeutic platform and have great potential to impact the treatment of surgical diseases.

Shape-Dependent Targeting of Injured Blood Vessels by Peptide Amphiphile Supramolecular Nanostructures.

Targeting of vascular intervention by systemically delivered supramolecular nanofibers after balloon angioplasty is described. Tracking of self-assembling peptide amphiphiles using fluorescence shows selective binding to the site of vascular intervention. Cylindrical nanostructures are observed to target the site of arterial injury, while spherical nanostructures with an equivalent diameter display no binding.

Incidence of acute lower extremity venous thrombosis after percutaneous endovascular aneurysm repair.

BACKGROUND: Improvements in endovascular aortic aneurysm repair (EVAR) have led many physicians to embrace a purely percutaneous approach using the suture-mediated "preclose" technique. Whereas there are a number of theoretical benefits, the rate of periprocedural iatrogenic acute deep venous thrombosis (DVT) is unknown. We sought to determine the incidence of acute DVT after percutaneous EVAR (PEVAR). METHODS: This was a single-center, retrospective review of 52 consecutive patients undergoing elective PEVAR. Demographics, procedural data, and postprocedure lower extremity venous duplex ultrasound data were analyzed by univariate statistical analysis. RESULTS: Among the 52 patients, the average age was 73 years, and the majority were men (n = 44). Only 6% (n = 3) had a prior history of DVT. The majority of procedures were performed under general anesthesia (n = 51 [98%]) with systemic intravenous heparin. Protamine was used in only 13 cases (25%). Sheath sizes ranged from 9F to 20F, with an average of 16F, and closure was achieved using the preclose technique. Postprocedure chemoprophylaxis was administered to 85% of patients (n = 44) during their hospitalization. Median length of stay was 1 day. Acute DVT was identified in 8% of patients (n = 4) on postoperative day 1. Among the 4 DVTs, 25% were femoropopliteal (n = 1) and 75% were calf vein DVTs (n = 3). On follow-up imaging 2 weeks later, 75% of DVTs were resolved. Among the four patients with acute DVT on postoperative day 1, three had associated risk factors: history of DVT (n = 2), active smokers (n = 1), and obesity (body mass index >30; n = 3). The remaining patient had no risk factors but developed an ipsilateral calf vein DVT. CONCLUSIONS: The risk of acute DVT after PEVAR is low. Lower extremity venous duplex ultrasound screening is not necessary unless there exist preclinical risk factors or postprocedural clinical indications suggestive of DVT.

Femoral vein blood flow during a total hip arthroplasty using a modified Heuter approach.

Several modifications to traditional surgical approaches for total hip arthroplasty (THA) have been introduced in an attempt to improve upon minimally invasive approaches and enhance short-term recovery. However, minimally invasive approaches are not without risk, including that of postoperative venous thromboembolism (VTE). There has been no published literature evaluating the femoral vein during an anterior approach. We aimed to study femoral vein blood flow using duplex ultrasonography during THA performed through a modified Heuter approach. Peek flow and vessel cross-sectional area were affected by limb position as well as acetabular and femoral retractor placement. No VTE was observed, but there was observed femoral vein compression, which may represent a risk of postoperative VTE similar to that seen in standard surgical approaches for THA.

Advanced Abdominal Aortic Aneurysm Modeling in Mice by Combination of Topical Elastase and Oral ß-aminopropionitrile.

The topical elastase murine model of abdominal aortic aneurysm (AAA) is enhanced when combined with ß-aminopropionitrile (BAPN)-supplemented drinking water to reliably produce true infrarenal aneurysms with behaviors that mimic human AAAs. Topically applying elastase to the adventitia of the infrarenal aorta causes structural damage to the elastic layers of the aortic wall and initiates aneurysmal dilation. Co-administering BAPN, a lysyl oxidase inhibitor, promotes sustained wall degeneration by reducing collagen and elastin crosslinking. This combination results in large AAAs that progressively expand, form intraluminal thrombus, and are capable of rupture. Refining surgical techniques, such as circumferentially isolating the entire infrarenal aortic segment, can help standardize the procedure for a consistent and thorough application of porcine pancreatic elastase despite different operators and anatomic variations between mice. Therefore, the elastase/BAPN model is a refined approach to surgically inducing AAA in mice, which may better recapitulate human aneurysms and provide additional opportunities to study aneurysm growth and rupture risk.

Compressive median neuropathy caused by brachial artery pseudoaneurysm.

Background: Brachial artery pseudoaneurysms (PSAs) are a rare complication of trauma and medical intervention, estimated to constitute 0.3-0.7% of all PSAs. Although neurologic symptoms are common in patients undergoing hemodialysis, direct nerve compression by large PSAs is rare. Case Description: We report a case of median nerve compression by a brachial artery PSA treated by PSA resection and distal nerve transfer of the extensor carpi radialis brevis nerve to the anterior interosseous nerve. Conclusion: This case illustrates the successful use of distal nerve transfers for the treatment of median neuropathy secondary to brachial PSA. In addition, this case highlights the importance of imaging before any exploratory nerve surgery in the setting of a mass and/or prior vascular procedure. Embarking on a nerve release/ repair surgery in the absence of a vascular surgeon would be disastrous.

Meniscus Allograft Transplantation Augmented With Autologous Bone Marrow Aspirate Concentrate.

Meniscus allograft transplantation (MAT) has been shown to be a feasible surgical option for younger patients, below 50 years of age who have meniscal insufficiency and have failed conservative treatment measures. In this technical note, we describe a procedure of harvesting and injecting bone marrow aspirate concentrate in a meniscus allograft during a MAT procedure, which may allow for longer lasting transplants and improve patient outcomes. In this technical note, bone marrow aspirate concentrate is harvested arthroscopically from the intercondylar notch at the surgical site, which prevents additional donor site morbidity, as seen with harvesting from other locations, such as the iliac crest. This also reduces operating time, since harvesting from the iliac crest requires different patient positioning and usually additional anesthesia. The authors of this surgical technique believe that biological augmentation during MATs will assist surgeons in maximizing graft survivorship and, ultimately, lead to better patient outcomes.

Creative Arts Therapy for Healthcare Professionals Is Associated With Long-Term Improvements in Psychological Distress.

OBJECTIVE: Burnout in healthcare professionals (HCPs) is a pressing issue in healthcare. We report the long-term impact of our previous creative arts therapy (CAT) intervention for reducing psychological distress in HCPs. METHODS: Healthcare professionals were randomized to CAT intervention or control group. The CAT group completed surveys evaluating symptoms of psychological distress at 4 months, 8 months, and 1 year postintervention, whereas the control group completed surveys at the 1-year mark. RESULTS: The CAT group demonstrated sustained improvement in distress scores for anxiety, depression, and affect at 4 and 8 months postintervention. At the 12-month mark, the CAT group exhibited improvements in anxiety, depression, and affect compared with the control group. CONCLUSION: Creative arts therapy has lasting benefits for HCPs. Long-term follow-ups are crucial for assessing sustainability, and further investigation should focus on disseminating and implementing CAT programs for HCPs.

Effectiveness of an Accelerated Rehabilitation Protocol After Tibial Tubercle Osteotomy.

Background: Patients with recurrent patellar dislocations with trochlear dysplasia are commonly treated surgically with a tibial tubercle osteotomy (TTO). Recovery and rehabilitation processes are often nonoperative out of concern for fixation failure or fracture. A more accelerated rehabilitation protocol allowing for early weightbearing and quadriceps strengthening may help to improve patient outcomes as long as complications are not increased. Purpose: To evaluate the safety and effectiveness of an accelerated weightbearing and early strengthening postoperative rehabilitation program for patients who undergo TTO. Study Design: Case series; Level of evidence, 4. Methods: Included were patients who underwent unilateral/staged bilateral TTO performed by a single surgeon between August 2013 and February 2018 with ≥6 months of follow-up. The surgical indication was primarily for patients with recurrent patellar instability. In all cases, a diagnostic arthroscopy was performed to evaluate the cartilage surfaces and document patellar tracking. The TTO was performed using a freehand technique and two 3.5-mm fully threaded screws for fixation. Patients underwent an accelerated postoperative rehabilitation program that allowed for weightbearing and lower extremity strengthening starting at 4 weeks. Objective and subjective outcome measures included any postoperative complications, knee range of motion, and patient-reported outcome scores (Kujala Anterior Knee Pain Scale [AKPS] and Knee injury and Osteoarthritis Outcome Score composite [(KOOS5]). Results: A total of 51 knees in 50 patients (38 female, 12 male) with a mean age of 31.24 ± 12.57 years were included in the final analysis. Compared with preoperative values, postoperative maximum knee flexion was significantly improved (117.67° ± 32.65° vs 131.12° ± 9.02°, respectively; P = .022). Postoperative complications included 6 patients with arthrofibrosis requiring manipulation under anesthesia, 4 with removal of symptomatic hardware, 1 tibial fracture (due to a fall), and 1 conversion to patellofemoral arthroplasty. The mean postoperative AKPS and KOOS5 scores were 72.98 ± 21.51 and 75.05 ± 16.02, respectively. Conclusion: Accelerated postoperative rehabilitation in TTO patients was an effective means of treatment with good subjective and objective outcomes and complication rates lower than traditional rehabilitation protocols.

Transient Exertional Compressive Radial Neuropathy in a Collegiate Baseball Pitcher: A Case Report.

CASE: A 21-year-old collegiate baseball pitcher presented with transient lateral arm pain and wrist extension weakness after pitching more than 1 inning. Physical examination was unremarkable at rest. Ultrasound-guided injection of the radial nerve at the level of the lateral intramuscular septum improved his symptoms. After decompression of the radial nerve, the patient noted resolution of his symptoms while pitching. CONCLUSION: Atraumatic radial neuropathy is a rare but documented phenomenon. As far as we know, this is the first reported case of a transient exertional radial neuropathy in an athlete at the level of the lateral intermuscular septum.

The Effect of Creative Arts Therapy on Psychological Distress in Health Care Professionals.

BACKGROUND: Work-related psychological distress is common among health care professionals. We determined whether 4 creative arts therapy (CAT) programs were acceptable, feasible, and improved psychological distress and job turnover intention in health care professionals with burnout symptoms. METHODS: Health care professionals were enrolled during the coronavirus disease (COVID-19) pandemic from September 2020 until July 2021. Participants attended in-person weekly 90-minute group session for 12 consecutive weeks. Intervention and control subjects completed surveys before the beginning and after the end of their cohort. The study outcomes were session attendance (feasibility), program satisfaction (acceptability), and change in symptoms of anxiety, depression, burnout, posttraumatic stress disorder (PTSD), and job turnover intention. RESULTS: We randomized 165 participants into 4 CAT interventions and 1 common control group across 3 sequential cohorts. Thirty-five randomized participants dropped out before the start of the cohort, and 16 were replaced from a waiting list. Therefore, the cohort consisted of 146 participants. On average, participants were 35 years old, white (85%), and female (92%). Overall, 52% were nurses, 10% were doctors, and 16% were behavioral health specialists. Participants attended a median of 9.5 [8-11] sessions. Program satisfaction was high with a median Client Satisfaction Questionnaire (CSQ-8) score of 31 [17-32] out of a possible score of 32. Participants randomized to the intervention had improvements in anxiety (P < .0001) and depression scores (P = .0007), total posttraumatic stress disorder score (P =.0002), burnout scores (P = .001, .003, .008), and turnover intention (P = .001). CONCLUSIONS: A CAT program is feasible, acceptable, and may reduce psychological distress and turnover intention for health care professionals.

Ankle brachial indices and anaerobes: is peripheral arterial disease associated with anaerobic bacteria in diabetic foot ulcers?

Background: Lower extremity amputations from diabetic foot ulcers (DFUs) are rebounding, and new biomarkers that predict wound healing are urgently needed. Anaerobic bacteria have been associated with persistent ulcers and may be a promising biomarker beyond currently recommended vascular assessments. It is unknown whether anaerobic markers are simply a downstream outcome of peripheral arterial disease (PAD) and ischemia, however. Here, we evaluate associations between two measures of anaerobic bacteria-abundance and metabolic activity-and PAD. Methods: We built a prospective cohort of 37 patients with baseline ankle brachial index (ABI) results. Anaerobic bacteria were measured in two ways: DNA-based total anaerobic abundance using 16S rRNA gene amplicon sequencing and resulting summed relative abundance, and RNA-based metabolic activity based on bacterial read annotation of metatranscriptomic sequencing. PAD was defined three ways: PAD diagnosis, ABI results, and a dichotomous definition of mild ischemia (versus normal) based on ABI values. Statistical associations between anaerobes and PAD were evaluated using univariate odds ratios (ORs) or Spearman's correlations. Results: Total anaerobe abundance was not significantly associated with PAD diagnosis, ABI results, or mild ischemia (ORPAD = 0.47, 95% CI = 0.023-7.23, p = 0.60; Spearman's correlation coefficientABI = 0.24, p = 0.17; ORmild ischemia = 0.25, 95% CI = 0.005-5.86, p = 0.42). Anaerobic metabolic activity was not significantly associated with PAD diagnosis, ABI results, or mild ischemia (ORPAD = 1.99, 95% CI = 0.17-21.44, p = 0.57; Spearman's correlation coefficientABI = 0.12, p = 0.52; ORmild ischemia = 0.90, 95% CI = 0.03-15.16, p = 0.94). Conclusion: Neither anaerobic abundance nor metabolic activity was strongly associated with our three definitions of PAD. Therefore, anaerobic bacteria may offer additional prognostic value when assessing wound healing potential and should be investigated as potential molecular biomarkers for DFU outcomes.

Partial open conversion with proximal aortic banding and endograft preservation is a safe option for the treatment of persistent type II endoleaks.

We have described our technique of open partial conversion (OPC; n = 5) with aortic banding and endograft preservation for the treatment of type II endoleaks. OPC significantly reduced the aortic clamping time (5.0 vs 32.5 minutes; P = .01) relative to endograft explantation (n = 2). Cross-clamping was avoided entirely in three of the procedures. The patients treated with OPC showed a trend toward a decreased operative time (4.8 vs 5.9 hours) and shorter hospital stay (5.7 vs 7.4 days). Follow-up computed tomography scans were available for three of the five OPC patients, which showed resolution of the type II endoleak. The findings from the present study have further demonstrated the safety of OPC for the treatment of type II endoleaks.

Corneal oxygen distribution with contact lens wear.

PURPOSE: Since 1991, multilayer mathematical in vivo oxygenation models have been created to predict normal corneal oxygenation with contact lens wear. From these models, there have been assertions that most hydrogel contact lenses allow 97%-98% of normal corneal oxygenation compared to no contact lens wear. In light of hydrogel lens-induced neovascularization and limbal hyperemia, to clinicians, this finding seems counterintuitive. This work seeks to validate or refute those preexisting models and estimate the impact of contact lens wear on the oxygen distribution profile across the cornea. To this end, to estimate the impact of contact lens wear on the 3-dimensional (3-D) oxygen distribution profile within the cornea as a function of the oxygen permeability of the contact lens, a two-dimensional axisymetric finite element analysis (FEA) model was constructed for contact lenses, on the cornea, both having varying thickness profiles. METHODS: A two dimensional (2-D) axi-symetric finite element analysis (FEA) model of a -3.00 D contact lens on eye was constructed. The model included the varying thickness profiles of the contact lens and cornea. By symmetry, this 2-D model is equivalent to a full 3-D model. The oxygen permeability, material thickness profile, and oxygen consumption coefficients from Brennan (Optometry and Vision Science, June 2005) were used for this validation. Several different oxygen consumption profiles were also considered. Oxygen partial pressure, flux, and consumption profiles were generated. RESULTS: Profiles of the oxygen partial pressure, flux, and consumption were generated from the central cornea to the limbal junction. CONCLUSION: This FEA model reproduced Brennan 8-layer model (BEL model) results at the central cornea. However, BEL model parameters yielded regions of oxygen deficiency in the corneal periphery, even in the open eye with no contact lens. If the BEL model cannot account for oxygenation across the whole cornea, it may be incorrect or incomplete. This assertion calls into question any conclusions from the BEL model regarding the minimum contact lens transmissibility needed to fully oxygenate the eye.

Targeted Nitric Oxide Delivery by Supramolecular Nanofibers for the Prevention of Restenosis After Arterial Injury.

AIMS: Cardiovascular interventions continue to fail as a result of arterial restenosis secondary to neointimal hyperplasia. We sought to develop and evaluate a systemically delivered nanostructure targeted to the site of arterial injury to prevent neointimal hyperplasia. Nanostructures were based on self-assembling biodegradable molecules known as peptide amphiphiles. The targeting motif was a collagen-binding peptide, and the therapeutic moiety was added by S-nitrosylation of cysteine residues. RESULTS: Structure of the nanofibers was characterized by transmission electron microscopy and small-angle X-ray scattering. S-nitrosylation was confirmed by mass spectrometry, and nitric oxide (NO) release was assessed electrochemically and by chemiluminescent detection. The balloon carotid artery injury model was performed on 10-week-old male Sprague-Dawley rats. Immediately after injury, nanofibers were administered systemically via tail vein injection. S-nitrosylated (S-nitrosyl [SNO])-targeted nanofibers significantly reduced neointimal hyperplasia 2 weeks and 7 months following balloon angioplasty, with no change in inflammation. INNOVATION: This is the first time that an S-nitrosothiol (RSNO)-based therapeutic was shown to have targeted local effects after systemic administration. This approach, combining supramolecular nanostructures with a therapeutic NO-based payload and a targeting moiety, overcomes the limitations of delivering NO to a site of interest, avoiding undesirable systemic side effects. CONCLUSION: We successfully synthesized and characterized an RSNO-based therapy that when administered systemically, targets directly to the site of vascular injury. By integrating therapeutic and targeting chemistries, these targeted SNO nanofibers provided durable inhibition of neointimal hyperplasia in vivo and show great potential as a platform to treat cardiovascular diseases.