Contemporary Outcomes of Open and Endovascular Intervention for Extracranial Carotid Artery Aneurysms: A Single Centre Experience.

OBJECTIVE: The objective of this study was to evaluate the outcomes of open surgery (OS) and endovascular surgery (ES) for extracranial carotid aneurysm (ECCA) in the authors' centre. METHODS: Fifty-seven consecutive patients who were diagnosed with ECCA and underwent intervention from January 2005 to July 2019 at Zhongshan Hospital, Fudan University, were reviewed retrospectively. Patient characteristics and surgical outcomes for OS and ES were analysed. ECCAs were divided into three morphological subgroups: subgroup Ⅰ, no severe tortuosity of the internal carotid artery (ICA) or common carotid artery (CCA) proximal to the aneurysm, tortuosity of the aneurysm and 1 cm of peri-aneurysmal carotid artery ≤ 90°; subgroup Ⅱ, severe ICA or CCA tortuosity proximal to the aneurysm, tortuosity of the aneurysm and 1 cm of peri-aneurysmal carotid artery ≤ 90°; subgroup Ⅲ, aneurysm tortuosity and 1 cm peri-aneurysmal carotid artery > 90°. RESULTS: 35 patients underwent OS, 20 patients underwent ES and 2 patients underwent OS after the failure of ES. Thirty-six cases were classified in subgroup Ⅰ, 11 cases in subgroup Ⅱ, and 10 cases in subgroup Ⅲ. ES was achieved successfully in all 18 cases of subgroup I, but failed in three of four cases in subgroups Ⅱ and Ⅲ. With a mean duration of 62.9 ± 44.5 months of follow up, five deaths were recorded in the OS group, two of which were caused by ipsilateral stroke and three were not neurologically related. There was no stroke or death in the ES group during follow up. One case of stroke and two cases of death occurred in symptomatic patients, while one case of stroke and three cases of death occurred in asymptomatic patients. CONCLUSION: This series demonstrates that ES may be a safe and durable option for ECCA in subgroup Ⅰ, while in subgroups Ⅱ and Ⅲ, ES alone may be difficult to apply. A 30 day stroke rate around 5% existed in ECCAs with interventions, which should be considered before the intervention.

In vitro platform establishes antigen-specific CD8+ T cell cytotoxicity to encapsulated cells via indirect antigen recognition.

The curative potential of non-autologous cellular therapy is hindered by the requirement of anti-rejection therapy. Cellular encapsulation within nondegradable biomaterials has the potential to inhibit immune rejection, but the efficacy of this approach in robust preclinical and clinical models remains poor. While the responses of innate immune cells to the encapsulating material have been characterized, little attention has been paid to the contributions of adaptive immunity in encapsulated graft destabilization. Avoiding the limitations of animal models, we established an efficient, antigen-specific in vitro platform capable of delineating direct and indirect host T cell recognition to microencapsulated cellular grafts and evaluated their consequential impacts. Using ovalbumin (OVA) as a model antigen, we determined that alginate microencapsulation abrogates direct CD8+ T cell activation by interrupting donor-host interaction; however, indirect T cell activation, mediated by host antigen presenting cells (APCs) primed with shed donor antigens, still occurs. These activated T cells imparted cytotoxicity on the encapsulated cells, likely via diffusion of cytotoxic solutes. Overall, this platform delivers unique mechanistic insight into the impacts of hydrogel encapsulation on host adaptive immune responses, comprehensively addressing a long-standing hypothesis of the field. Furthermore, it provides an efficient benchtop screening tool for the investigation of new encapsulation methods and/or synergistic immunomodulatory agents.

Comparison of Ultrasound-Guided Thrombin Injection of Iatrogenic Pseudoaneurysms Based on Neck Dimension.

BACKGROUND: Ultrasound-guided thrombin injection (UGTI) of femoral artery pseudoaneurysms after endovascular procedures is an effective therapy. There is controversy in the literature regarding injecting pseudoaneurysms with short and/or wide necks. This article reports our experience in UGTI of pseudoaneurysms in 1 hospital regarding the efficacy of this treatment in all pseudoaneurysms regardless of the size of the necks. METHODS: A retrospective review of 46 patients diagnosed between 2011 and 2016 with groin pseudoaneurysms using established duplex ultrasound criteria. Mean age was 68 years (range 27-87). Ten pseudoaneurysms thrombosed spontaneously, 5 were thrombosed by ultrasound-guided compression, and 2 were treated surgically due to disqualifying criteria. In this retrospective review, we analyzed the remaining 29 pseudoaneurysms regarding the dimensions of their neck lengths and outcomes after attempting thrombin injection. RESULTS: The mean aneurysm neck length and width were 1.03 ± 0.9 cm and 0.30 ± 0.1 cm, respectively. All 29 patients were evaluated with respect to pseudoaneurysm size, neck length, neck width, and complexity. Successful treatment of 29 pseudoaneurysms (2 external iliac, 20 common femoral, 2 deep femoral, and 5 superficial femoral) with UGTI was achieved without complications in 100% of the cases, regardless of pseudoaneurysm size, neck dimensions, or complexity. Anticoagulation status did not affect the efficacy of the procedure. Nine of the 29 pseudoaneurysms (31.0%) had neck length less than 0.5 cm. CONCLUSIONS: This study demonstrates the safety and efficacy of UGTI in treating iatrogenic pseudoaneurysm in 29 of 29 patients, even in patients with pseudoaneurysm with short neck lengths. Our experiences support injecting all pseudoaneurysms irrespective of dimension.

Admission Hyperglycemia Predicts Infectious Complications After Burns.

Inflammation and hypermetabolism post burn predisposes to hyperglycemia and insulin resistance. The authors hypothesize that admission hyperglycemia predicts infectious outcomes. A retrospective review of all patients greater than 20 years of age admitted for initial burn management from January 2008 to December 2013 was conducted. Nonthermal injuries, transfers, and those without admission glucose or histories were excluded. Hyperglycemia was defined as admission glucose ≥150 mg/dl. Patients were grouped as follows: euglycemic without diabetes (control), euglycemic with diabetes (-H+D), hyperglycemic without diabetes (+H-D), and hyperglycemic with diabetes (+H+D). Outcomes included infection, mortality, length of stay, and disposition. Comparisons were made using Fisher's exact test and multiple logistic regression. A total of 411 patients were analyzed. No significant differences between any of the groups and controls were noted in race, inhalation injury, or obesity. All three groups had higher mortality compared with controls. Longer hospital stays were noted only in +H-D. +H-D and +H+D were less likely to be discharged home than controls. +H-D had higher rates of bacteremia, +H-D and +H+D had higher rates of pneumonia, and -H+D and +H-D had higher rates of urinary tract infection. Regression for infection and mortality outcomes with TBSA, age, diabetes, hyperglycemia, obesity, race, gender, and inhalation injury as covariates was performed. Hyperglycemia was the only independent predictor of bacteremia (area under curve [AUC] = 0.736). Hyperglycemia was also a predictor of pneumonia and urinary tract infection (AUC = 0.766 and 0.802, respectively). The only independent predictors of mortality were age, TBSA, and inhalation injury (AUC = 0.892). Acute glucose dysregulation may be more important than diabetes in predicting infectious outcomes after burns. Therefore, admission glucose may have prognostic value.

Controlled Release of Dexamethasone from Organosilicone Constructs for Local Modulation of Inflammation in Islet Transplantation.

Inflammation is a significant detriment to the engraftment of cells and tissues, particularly for islet transplantation, where a low tolerance for the inflammatory milieu results in significant graft loss. Local treatment with anti-inflammatories, such as glucocorticoids, provides the benefits of site-targeted delivery with minimization of the broad side effects associated with systemic delivery. Polydimethylsiloxane (PDMS) is a flexible platform that is capable of providing sustained delivery of hydrophobic drugs. Here, we evaluated the capacity of PDMS constructs loaded with the anti-inflammatory glucocorticoid dexamethasone (Dex) to locally mitigate inflammation in islet grafts. Dex-PDMS constructs, fabricated in rod or disk geometries, demonstrated prolonged and sustained release at therapeutically relevant levels. In vitro, Dex-PDMS constructs inhibited endotoxin-induced human monocyte and macrophage activation, but they did not impair islet viability or function. Dex-PDMS rods, co-transplanted with islet-seeded scaffolds in a murine model, demonstrated suppression of host inflammatory responses during early- and late-phase engraftment, without significantly altering islet graft potency. The facile nature of these glucocorticoid-doped PDMS constructs allows for the optimization of targeted dose delivery with wide applicability in cell and tissue transplantation.

Engineering biomimetic materials for islet transplantation.

A closed-loop system that provides both the sensing of glucose and the appropriate dosage of insulin could dramatically improve treatment options for insulin-dependent diabetics. The intrahepatic implantation of allogeneic islets has the potential to provide this intimate control, by transplanting the very cells that have this inherent sensing and secretion capacity. Limiting islet transplantation, however, is the significant loss and dysfunction of islets following implantation, due to the poor engraftment environment and significant immunological attack. In this review, we outline approaches that seek to address these challenges via engineering biomimetic materials. These materials can serve to mimic natural processes that work toward improving engraftment, minimizing inflammation, and directing immunological responses. Biomimetic materials can serve to house cells, recapitulate native microenvironments, release therapeutic agents in a physiological manner, and/or present agents to direct cells towards desired responses. By integrating these approaches, superior platforms capable of improving long-term engraftment and acceptance of transplanted islets are on the horizon.

Local administration of ß-blockers for infantile hemangiomas: a systematic review and meta-analysis.

BACKGROUND: Infantile hemangiomas (IHs) are a common pediatric lesion. Orally administered ß-blockers have been reported as effective in treating these lesions. However, oral administration is also associated with systemic adverse effects. Treatment with locally administered ß-blockers may provide acceptable efficacy with lower incidence of adverse effects. This may offer a better first-line treatment. METHODS: PubMed was searched through March 2014 for studies reporting patient-level response of 5 or more patients treated with intralesional propranolol, topical timolol, or topical propranolol for cutaneous IHs. Rates of response to treatment, defined as clinically significant regression, were combined using random-effects meta-analysis. RESULTS: Ninety-four articles were identified. Seventeen articles met the study criteria. These studies primarily focused on superficial IHs. Response rates for topical propranolol and topical timolol were not significantly different, 76% [95% confidence interval (CI), 62%-86%] and 83% (95% CI, 65%-93%), respectively (P=0.45). Prospectively conducted studies reported lower response rates compared to retrospective studies for both topical propranolol (P=0.06) and topical timolol (P<0.01). When only prospectively conducted studies were included, response rates for topical propranolol and topical timolol were not significantly different, 72% (95% CI, 57%-83%) and 72% (95% CI, 53%-86%), respectively (P=0.98). Significant adverse effects were rare. Only 1 case of sleep disturbance was reported across 554 patients from all studies. CONCLUSIONS: Topically administered ß-blockers are an effective treatment for superficial IHs that pose few adverse effects and should be considered for primary treatment.