Photochemical Tissue Passivation of Arteriovenous Grafts Prevents Long-Term Development of Intimal Hyperplasia in a Swine Model.

BACKGROUND: The autologous vein remains the standard conduit for lower extremity and coronary artery bypass grafting despite a 30%-50% 5-y failure rate, primarily attributable to intimal hyperplasia (IH) that develops in the midterm period (3-24 mo) of graft maturation. Our group discovered that externally strengthening vein grafts by cross-linking the adventitial collagen with photochemical tissue passivation (PTP) mitigates IH in an arteriovenous model at 4 wk. We now investigate whether this effect is retained in the midterm period follow-up. METHODS: Six Hanford miniature pigs received bilateral carotid artery interposition vein grafts. In each animal, the external surface of one graft was treated with PTP before grafting, whereas the opposite side served as the untreated control. The grafts were harvested after 3 mo. Ultrasound evaluation of all vein grafts was performed at the time of grafting and harvest. The grafts were also evaluated histomorphometrically and immunohistologically for markers of IH. RESULTS: All vein grafts were patent at 3 mo except one graft in the PTP-treated group because of early technical failure. The control vein grafts had significantly greater IH than PTP-treated grafts at 3 mo, as evidenced by the intimal area (2.6 ± 1.0 mm2versus 1.4 ± 1.5 mm2, respectively, P = 0.045) and medial area (5.1 ± 1.9 mm2versus 2.7 ± 2.4 mm2, respectively, P = 0.048). The control grafts had an increased presence and proliferation of mural myofibroblasts with greater smooth muscle actin and proliferating cell nuclear antigen staining. CONCLUSIONS: PTP treatment to the external surface of the vein grafts decreases IH at 3 mo after arteriovenous grafting and may prevent future graft failure.

Photochemical Tissue Passivation Prevents Contracture of Full Thickness Wounds in Mice.

BACKGROUND AND OBJECTIVES: Wound contracture formation from excessive myofibroblast activity can result in debilitating morbidities. There are currently no treatments to prevent contracture. Photochemical tissue passivation (PTP), an established, safe, and user-friendly treatment modality, crosslinks collagen by a light-activated process, thus modulating the wound healing response and scarring. We hypothesised that PTP treatment would reinforce wounds by blunting the fibrotic response thus limiting contracture. STUDY DESIGN/MATERIALS AND METHODS: Full-thickness, 1 cm × 1 cm excisional wounds were created on the dorsum of 32 C57BL/6 mice. Treated wounds were painted with photosensitizing dye and exposed to visible light. Wounds were serially photographed over 6 weeks to measure wound contracture. At 7, 14, 21, and 42 days after wound creation, mice were euthanized and wounds were harvested for histologic review by a dermatopathologist. RESULTS: By Day 7, control wounds had significantly more contracture than those treated with PTP (33.0 ± 17.1% and 19.3 ± 9.0%, respectively; P = 0.011). PTP-treated wounds maintained approximately 20% less contracture than controls from Day 14 and on (P < 0.05). By Day 42, wounds had contracted by 86.9 ± 5.5% in controls and 64.2 ± 3.2% in PTP-treated wounds (P < 0.03). Histologically, PTP wounds had earlier growth and development of dermal collagen, neovascularization, and development of skin appendages, compared with control wounds. CONCLUSIONS: PTP significantly limits contracture of full-thickness wounds and improves wound healing. PTP-treated wounds histologically demonstrate more mature structural organization than untreated wounds and closely resemble native skin. PTP treatment may be applicable not only for excisional wounds, but also for wounds with a high incidence of contracture and associated morbidity. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Laser Ablation Facilitates Implantation of Dynamic Self-Regenerating Cartilage for Articular Cartilage Regeneration.

OBJECTIVES: This study investigated a novel strategy for improving regenerative cartilage outcomes. It combines fractional laser treatment with the implantation of neocartilage generated from autologous dynamic Self-Regenerating Cartilage (dSRC). METHODS: dSRC was generated in vitro from harvested autologous swine chondrocytes. Culture was performed for 2, 4, 8, 10, and 12 weeks to study matrix maturation. Matrix formation and implant integration were also studied in vitro in swine cartilage discs using dSRC or cultured chondrocytes injected into CO2 laser-ablated or mechanically punched holes. Cartilage discs were cultured for up to 8 weeks, harvested, and evaluated histologically and immunohistochemically. RESULTS: The dSRC matrix was injectable by week 2, and matrices grew larger and more solid with time, generating a contiguous neocartilage matrix by week 8. Hypercellular density in dSRC at week 2 decreased over time and approached that of native cartilage by week 8. All dSRC groups exhibited high glycosaminoglycan (GAG) production, and immunohistochemical staining confirmed that the matrix was typical of normal hyaline cartilage, being rich in collagen type II. After 8 weeks in cartilage lesions in vitro, dSRC constructs generated a contiguous cartilage matrix, while isolated cultured chondrocytes exhibited only a sparse pericellular matrix. dSRC-treated lesions exhibited high GAG production compared to those treated with isolated chondrocytes. CONCLUSIONS: Isolated dSRC exhibits hyaline cartilage formation, matures over time, and generates contiguous articular cartilage matrix in fractional laser-created microenvironments in vitro, being well integrated with native cartilage.

Patient Pain Sketches Can Predict Surgical Outcomes in Trigger-Site Deactivation Surgery for Headaches.

BACKGROUND: Patient selection for headache surgery is an important variable to ensure successful outcomes. In the authors' experience, a valuable method to visualize pain/trigger sites is to ask patients to draw their pain. The authors have found that there are pathognomonic pain patterns for each site, and typically do not operate on patients with atypical pain sketches, as they believe such patients are poor surgical candidates. However, a small subset of these atypical patients undergo surgery based on other strong clinical findings. In this study, the authors attempt to quantify this clinical experience. METHODS: Patients were prospectively enrolled and completed pain sketches at screening. One hundred six diagrams were analyzed/categorized by two independent, blinded reviewers as follows: (1) typical (pain over nerve distribution, expected radiation); (2) intermediate (pain over nerve distribution, atypical radiation); or (3) atypical (pain outside of normal nerve distribution, atypical radiation). Preoperative and postoperative Migraine Headache Index was compared between subgroups using unpaired t tests. RESULTS: Migraine Headache Index improvement was 73 ± 38 percent in the typical group, 78 ± 30 percent in the intermediate group, and 30 ± 40 percent in the atypical group. There was a significant difference in Migraine Headache Index between the typical and atypical groups (p = 0.03) and between the intermediate and atypical groups (p < 0.01). The chance of achieving Migraine Headache Index improvement greater than 30 percent in the atypical group was 20 percent. CONCLUSIONS: Patient pain sketches classified as atypical (facial pain, atypical pain point origin, diffuse pain) can predict poor outcomes in headache surgery. As the authors continue to develop patient selection criteria for headache surgery, patient sketches should be considered as an effective, cheap, and simple-to-interpret tool for selecting candidates for surgery.

The state of the union: Nationwide absence of uniform guidelines for the prehospital use of tourniquets to control extremity exsanguination.

BACKGROUND: After the Sandy Hook shootings and the resulting Hartford Consensus, as well as the recent Boston Marathon bombing, the need for a uniform, detailed, and aggressive prehospital extremity exsanguination control protocol became clear. We hypothesized that most states within the United States lack a detailed uniform protocol. METHODS: We performed a systematic nationwide assessment of emergency medical services (EMS) prehospital extremity exsanguination control protocols. An online search (updated February 7, 2015) identified state-, region-, or county-specific EMS protocols in all 50 states. If unavailable online, protocols were retrieved directly by contacting each state's Department of Public Health (or other appropriate agency). Two investigators independently screened each extremity exsanguination control protocol. Protocols were first grouped into three categories: I, tourniquet not mentioned; II, tourniquet mentioned, without specific guidance; III, tourniquet mentioned, with specific guidance related to type, indications, application technique, and safety concerns. Each protocol was then scored on a five-point scale for comparison. RESULTS: Forty-two states (84%) had statewide and 14 (28%) had at least one county-specific protocol. Seven states (16%) had no statewide protocol but at least one county-specific protocol (range, 1-10). Mississippi had neither statewide nor county-specific protocols. Of statewide protocols, 4 (9.5%) were in Category I, 23 (54.8%) in Category II, and 15 (35.7%) in Category III. The mean score for statewide tourniquets was 2.4/5 (SD, 1.25; range, 0-5). Thirteen (31%) statewide protocols referred to "commercial" or "approved" tourniquets; only three (7%) recommended a particular commercial device. The mean score for the county-specific protocols of states with no statewide protocol was 3.10 (SD, 1.56; range, 0-5) CONCLUSIONS: Throughout the United States, there is considerable variability in EMS protocols addressing the management of extremity exsanguination and an alarming absence of specific guidance for tourniquet use. Most states do not have a uniform, detailed, and aggressive prehospital extremity exsanguination control protocol. LEVEL OF EVIDENCE: Epidemiologic and prognostic study, level III.

Diagnosis and deployment of a self-expanding foam for abdominal exsanguination: Translational questions for human use.

BACKGROUND: We have previously described the hemostatic efficacy of a self-expanding polyurethane foam in lethal venous and arterial hemorrhage models. A number of critical translational questions remain, including prehospital diagnosis of hemorrhage, use with diaphragmatic injury, effects on spontaneous respiration, the role of omentum, and presence of a laparotomy on foam properties. METHODS: In Experiment 1, diagnostic blood aspiration was attempted through a Veress needle before foam deployment during exsanguination (n = 53). In Experiment 2: a lethal hepatoportal injury/diaphragmatic laceration was created followed by foam (n = 6) or resuscitation (n = 10). In Experiment 3, the foam was deployed in naïve, spontaneously breathing animals (n = 7), and respiration was monitored. In Experiments 4 and 5, the foam was deployed above (n = 6) and below the omentum (n = 6) and in naïve animals (n = 6). Intra-abdominal pressure and organ contact were assessed. RESULTS: In Experiment 1, blood was successfully aspirated from a Veress needle in 70% of lethal iliac artery injuries and 100% of lethal hepatoportal injuries. In Experiment 2, in the presence of a diaphragm injury, between 0 cc and 110 cc of foam was found within the pleural space. Foam treatment resulted in a survival benefit relative to the control group at 1 hour (p = 0.03). In Experiment 3, hypercarbia was observed: mean (SD) Pco2 was 48 (9.4) mm Hg at baseline and 65 (14) mm Hg at 60 minutes. In Experiment 4, abdominal omentum seemed to influence organ contact and transport in two foam deployments. In Experiment 5, there was no difference in intra-abdominal pressure following foam deployment in the absence of a midline laparotomy. CONCLUSION: In a series of large animal studies, we addressed key translational issues surrounding safe use of foam treatment. These additional data, from diagnosis to deployment, will guide human experiences with foam treatment for massive abdominal exsanguination where no other treatments are available.