Pathogenesis of Thromboembolism and Endovascular Management.

Venous thromboembolism (VTE), a disease that includes deep venous thrombosis (DVT) and pulmonary embolism (PE), is associated with high mortality, morbidity, and costs. It can result in long-term complications that include postthrombotic syndrome (PTS) adding to its morbidity. VTE affects 1/1000 patients, costs $13.5 billion annually to treat, and claims 100,000 lives annually in the US. The current standard of care for VTE is anticoagulation, though thrombolysis may be performed in patients with PE and threatened limb. This review discusses pathogenesis and medical treatment of VTE and then focuses on endovascular treatment modalities. Mechanical- and catheter-directed thrombolysis (CDT) is discussed, as well as patient selection criteria, and complications. The first prospective study (CaVenT) comparing CDT with anticoagulation alone in acute DVT, despite study shortcomings, corroborates the existing literature indicating improved outcomes with CDT. The potential of the ongoing prospective, multicenter, randomized ATTRACT trial is also highlighted.

Indocyanine green laser angiography improves deep inferior epigastric perforator flap outcomes following abdominal suction lipectomy.

BACKGROUND: The reliability of deep inferior epigastric artery perforator (DIEP) flap reconstruction following abdominal liposuction is controversial. The authors' early cases were technically successful; however, they experienced high partial flap loss and fat necrosis rates. The authors sought to compare DIEP flap outcomes in the setting of prior liposuction after the use of intraoperative indocyanine green angiography compared to when flaps were assessed on clinical grounds alone. METHODS: A retrospective review of a consecutive series of DIEP flaps following liposuction at a single institution was performed, comparing those evaluated on clinical grounds alone and those in which indocyanine green angiography was used intraoperatively. Outcomes measured included anastomotic complications, total flap loss, partial flap loss, fat necrosis, and postoperative abdominal wounds. RESULTS: Thirteen DIEP flaps following prior liposuction were performed on 11 patients from July of 2003 through January of 2014. All patients had preoperative imaging with duplex ultrasound or computed tomographic angiography to analyze perforator suitability before surgical exploration. Seven flaps were evaluated intraoperatively on clinical grounds alone. Six flaps were assessed and modified based on indocyanine green angiography. All flaps were successful; however, partial flap loss and fat necrosis rates dropped from 71.4 percent to 0 percent when indocyanine green angiography was used intraoperatively (p = 0.02). CONCLUSIONS: Indocyanine green angiography is an excellent vascular imaging modality for intraoperative use to assess flap perfusion, and improves outcomes in DIEP flaps when harvested after prior abdominal suction lipectomy.

Laser welding of ruptured intestinal tissue using plasmonic polypeptide nanocomposite solders.

Approximately 1.5 million people suffer from colorectal cancer and inflammatory bowel disease in the United States. Occurrence of leakage following standard surgical anastomosis in intestinal and colorectal surgery is common and can cause infection leading to life-threatening consequences. In this report, we demonstrate that plasmonic nanocomposites, generated from elastin-like polypeptides (ELPs) cross-linked with gold nanorods, can be used to weld ruptured intestinal tissue upon exposure to near-infrared (NIR) laser irradiation. Mechanical properties of these nanocomposites can be modulated based on the concentration of gold nanorods embedded within the ELP matrix. We employed photostable, NIR-absorbing cellularized and noncellularized GNR-ELP nanocomposites for ex vivo laser welding of ruptured porcine small intestines. Laser welding using the nanocomposites significantly enhanced the tensile strength, leakage pressure, and bursting pressure of ruptured intestinal tissue. This, in turn, provided a liquid-tight seal against leakage of luminal liquid from the intestine and resulting bacterial infection. This study demonstrates the utility of laser tissue welding using plasmonic polypeptide nanocomposites and indicates the translational potential of these materials in intestinal and colorectal repair.

Investigation of phase separation behavior and formation of plasmonic nanocomposites from polypeptide-gold nanorod nanoassemblies.

Genetically engineered elastin-like polypeptides (ELP) can be interfaced with cetyltrimethyl ammonium bromide (CTAB)-stabilized gold nanorods (GNRs) resulting in the formation of stable dispersions (nanoassemblies). Increasing the dispersion temperature beyond the ELP transition temperature results in phase separation and formation of solid-phase ELP-GNR matrices (nanocomposites). Here, we investigated different physicochemical conditions that influence nanocomposite formation from temperature-induced phase separation of ELP-GNR nanoassemblies. The presence of cetyltrimethyl ammonium bromide (CTAB), used to template the formation of gold nanorods, plays a significant role in the phase separation behavior, with high concentrations of the surfactant leading to dramatic enhancements in ELP transition temperature. Nanocomposites could be generated at 37 °C in the presence of low CTAB concentrations (<1.5 mM); higher concentrations of CTAB necessitated higher temperatures (60 °C) due to elevated transition temperatures. The concentration of gold nanorods, however, had minimal influence on the phase separation behavior and nanocomposite formation. Further analysis of the kinetics of nanocomposite formation using a mathematical model indicated that CTAB largely influenced the early event of coacervation of ELP-GNR nanoassemblies leading to nanocomposites, but had minimal effect on nanocomposite maturation, which is a later-stage longer event. Finally, nanocomposites prepared in the presence of low CTAB concentrations demonstrated a superior photothermal response following laser irradiation compared to those generated using higher CTAB concentrations. Our results on understanding the formation of plasmonic/photothermal ELP-GNR nanocomposites have significant implications for tissue engineering, regenerative medicine, and drug delivery.

Synergistic administration of photothermal therapy and chemotherapy to cancer cells using polypeptide-based degradable plasmonic matrices.

AIM: Resistance of cancer cells to hyperthermic temperatures and spatial limitations of nanoparticle-induced hyperthermia necessitates the identification of effective combination treatments that can enhance the efficacy of this treatment. Here we show that novel polypeptide-based degradable plasmonic matrices can be employed for simultaneous administration of hyperthermia and chemotherapeutic drugs as an effective combination treatment that can overcome cancer cell resistance to hyperthermia. METHOD: Novel gold nanorod elastin-like polypeptide matrices were generated and characterized. The matrices were also loaded with the heat-shock protein (HSP)90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), currently in clinical trials for different malignancies, in order to deliver a combination of hyperthermia and chemotherapy. RESULTS: Laser irradiation of cells cultured over the plasmonic matrices (without 17-AAG) resulted in the death of cells directly in the path of the laser, while cells outside the laser path did not show any loss of viability. Such spatial limitations, in concert with expression of prosurvival HSPs, reduce the efficacy of hyperthermia treatment. 17-AAG-gold nanorod-polypeptide matrices demonstrated minimal leaching of the drug to surrounding media. The combination of hyperthermic temperatures and the release of 17-AAG from the matrix, both induced by laser irradiation, resulted in significant (>90%) death of cancer cells, while 'single treatments' (i.e., hyperthermia alone and 17-AAG alone) demonstrated minimal loss of cancer cell viability (<10%). CONCLUSION: Simultaneous administration of hyperthermia and HSP inhibitor release from plasmonic matrices is a powerful approach for the ablation of malignant cells and can be extended to different combinations of nanoparticles and chemotherapeutic drugs for a variety of malignancies.