[In searching for perfect blood substitute. Creation and application of perftorane]. / V poiskakh ideal'nogo krovezamenitelya. Sozdanie i primenenie perftorana.

The article is devoted to historiography of perfluorocarbons, as well as discoverers of perftorane and their discoveries. There would be no national priority in transfusiology without these discoveries. Perftorane is the only one of the world series of perfluorocarbon emulsion drugs that has passed all phases of clinical trials. Perftorane has been used in clinical medicine for 30 years.

Perfluorocarbon-based oxygen carriers: from physics to physiology.

Developing biocompatible, synthetic oxygen carriers is a consistently challenging task that researchers have been pursuing for decades. Perfluorocarbons (PFC) are fascinating compounds with a huge capacity to dissolve gases, where the respiratory gases are of special interest for current investigations. Although largely chemically and biologically inert, pure PFCs are not suitable for injection into the vascular system. Extensive research created stable PFC nano-emulsions that avoid (i) fast clearance from the blood and (ii) long organ retention time, which leads to undesired transient side effects. PFC-based oxygen carriers (PFOCs) show a variety of application fields, which are worthwhile to investigate. To understand the difficulties that challenge researchers in creating formulations for clinical applications, this review provides the physical background of PFCs' properties and then illuminates the reasons for instabilities of PFC emulsions. By linking the unique properties of PFCs and PFOCs to physiology, it elaborates on the response, processing and dysregulation, which the body experiences through intravascular PFOCs. Thereby the reader will receive a scientific and easily comprehensible overview why PFOCs are precious tools for so many diverse application areas from cancer therapeutics to blood substitutes up to organ preservation and diving disease.

How could perfluorocarbon affect cytokine storm and angiogenesis in coronavirus disease 2019 (COVID-19): role of hypoxia-inducible factor 1α.

Coronavirus disease 2019 (COVID-19) pandemic is still a world-class challenge. Inflammation, especially its severe form with excess release of pro-inflammatory cytokines (cytokine storm) which is a life-threatening condition, is among the most important suspects involved in COVID-19 pathogenesis. It has been shown that cytokine storm could cause notable morbidities such as acute respiratory distress syndrome (ARDS) which leads to hypoxia which is significantly associated with mortality of patients with COVID-19. Hypoxia-inducible factor 1α (HIF-1α) which activates following ARDS-induced hypoxia plays a crucial role in pathogenesis of cytokine storm. The expression of tumor necrosis factor α (TNF-α), interleukin 1 ß (IL-1ß), and IL-6 which are key elements of cytokine storm are by nuclear factor κß (NFκB). Interestingly, during the hypoxia, HIF-1α activates NFκB to induce expression of pro-angiogenic and pro-inflammatory factors. These released factors starts a autocrine/paracrine loop and causes deterioration of their etiological pathways of expression: cytokine storm and ARDS. To sum up, it seems HIF-1α is an important target to hit to ameliorate the mentioned pathways. Herein, we suggest perfluorocarbons (PFCs) which are among the organofluorine compounds as a possible co-treatment to reduce hypoxemia and then hypoxia. These substances are known for their high gas solving potential that make them able to be used as a synthetic artificial blood product. Due to the potential of PFCs to affect the fountain of important physiopathological pathway such as inflammation a hypoxia through affecting NFκB, they could be considered as multi-target co-treatment for ARD individuals with COVID-19. It is highly suggested to evaluate this hypothesis in following researches.

The effect of the perfluorocarbon emulsion Oxycyte™ in an ovine model of severe decompression illness.

Background: The treatment of decompression sickness (DCS) with hyperbaric oxygen (HBO2) serves to decrease intravascular bubble size, increase oxygen (O2) delivery to tissue and enhance the elimination of inert gas. Emulsified perfluorocarbons (PFC) combined with breathing O2 have been shown to have similar effects animal models. We studied an ovine model of severe DCS treated with the intravenous PFC Oxycyte™ while breathing O2 compared to saline control also breathing O2. Methods: Juvenile male sheep (N=67; weight 24.4±2.10kg) were compressed to 257 feet of sea water (fsw) in our multiple large-animal chamber where they remained under pressure for 31 minutes. Animals then were decompressed to surface pressure and randomized to receive either Oxycyte at 5mL/kg intravenously (IV) or 5mL/kg saline IV (both receiving 100% O2) 10 minutes after reaching surface pressure. Mortality was recorded at two hours, four hours, and 24 hours after receiving the study drug. Surviving animals underwent perfusion fixation and harvesting of the spinal cord at 24 hours. Spinal cord sections were assessed for volume of lesion area and compared. Results: There was no significant difference in survival at two hours (p=0.2737), four hours (p=0.2101), or 24 hours (p=0.3171). Paralysis at 24 hours was not significantly different. However, spinal cord lesion area was significantly smaller in the Oxycyte group as compared to the saline group, with median spinal cord lesion areas 0.65% vs. 0.94% (p=0.0107). Conclusion: In this ovine model of severe DCS the intravenous PFC Oxycyte did not reduce mortality but did ameliorate spinal cord injury when used after the onset of DCS.

Use of intra-procedural fusion imaging combining contrast-enhanced ultrasound using a perflubutane-based contrast agent and auto sweep three-dimensional ultrasound for guiding radiofrequency ablation and evaluating its efficacy in patients with hepatocellular carcinoma.

Purpose: This study evaluated the usefulness of intraprocedural contrast-enhanced ultrasound (CEUS)/ultrasound (US) fusion imaging using a perflubutane-based contrast agent combined with preprocedural auto sweep three-dimensional US to obtain volume data for guidance and evaluation of the therapeutic efficacy of radiofrequency ablation (RFA).Methods: This uncontrolled clinical trial included 50 hepatocellular carcinomas (HCCs) with a mean diameter of 15.3 mm that had been treated by RFA. The efficacy of RFA was evaluated by CEUS/US fusion imaging during the procedure. If the ablation was deemed to be inadequate, further ablation was performed until adequate ablation was achieved. Contrast-enhanced computed tomography (CECT) or contrast-enhanced magnetic resonance imaging (CEMRI) was performed a month after RFA, and the images obtained using each modality were reviewed to evaluate the efficacy of RFA.Results: Thirty-three of the 50 lesions were evaluated by CEUS/US fusion imaging as having been adequately ablated after the first RFA procedure. The ablation was evaluated as inadequate in the remaining 17 lesions, for which additional ablation was performed. Ninety-eight (49/50) of all HCCs were evaluated as having been eventually adequately ablated on intraprocedural CEUS/US fusion imaging. The concordance rate for evaluations between intraprocedural CEUS/US fusion imaging and CECT/CEMRI performed 1 month after RFA was 88% (44/50). The kappa value for agreement between the two methods of evaluation was 0.792.Conclusion: Intraprocedural fusion imaging combining CEUS and auto sweep three-dimensional US appears to be a useful modality for RFA guidance and evaluation of therapeutic efficacy of RFA in patients with HCC.

Semifluorinated Alkane Eye Drops in Chronic Ocular Graft-versus-Host Disease: A Prospective, Multicenter, Noninterventional Study.

PURPOSE: Ocular graft-versus-host disease (oGvHD) following allogeneic hematopoietic stem cell transplantation develops as severe dry eye disease (DED) and is initially treated with lubricants, although no clinical trials are available using artificial tears in oGvHD. This trial was set up to test perfluorohexyloctane (NovaTears®) as nonpreserved layer-forming agent for the treatment of DED in oGvHD. METHODS: 25 patients with severe DED due to oGvHD received 1 drop perfluorohexyloctane 4 times daily during a prospective, multicenter, observational 12-week study on top of established topical therapy. Clinical parameters included Schirmer test, tear film breakup time, corneal staining, meibum secretion and ocular surface disease index. Adverse events, visual acuity and intraocular pressure were key safety parameters. RESULTS: From 25 patients recruited, 23 presented for the second visit. Perfluorohexyloctane treatment did not lead to any changes in clinical or safety parameters but led to fast relief in symptoms in 57% of the patients. One adverse reaction occurred. CONCLUSIONS: This study showed no change in clinical signs in severe DED due to oGvHD, which was not unexpected due to the underlying pathomechanisms. However, the study showed improvement of symptoms in individual patients allowing application of perfluorohexyloctane as an additional symptomatic therapy in oGvHD.

Optimized and accelerated 19 F-MRI of inhaled perfluoropropane to assess regional pulmonary ventilation.

PURPOSE: To accelerate 19 F-MR imaging of inhaled perfluoropropane using compressed sensing methods, and to optimize critical scan acquisition parameters for assessment of lung ventilation properties. METHODS: Simulations were performed to determine optimal acquisition parameters for maximal perfluoropropane signal-to-noise ratio (SNR) in human lungs for a spoiled gradient echo sequence. Optimized parameters were subsequently employed for 19 F-MRI of inhaled perfluoropropane in a cohort of 11 healthy participants using a 3.0 T scanner. The impact of 1.8×, 2.4×, and 3.0× undersampling ratios on 19 F-MRI acquisitions was evaluated, using both retrospective and prospective compressed sensing methods. RESULTS: 3D spoiled gradient echo 19 F-MR ventilation images were acquired at 1-cm isotropic resolution within a single breath hold. Mean SNR was 11.7 ± 4.1 for scans acquired within a single breath hold (duration = 18 s). Acquisition of 19 F-MRI scans at shorter scan durations (4.5 s) was also demonstrated as feasible. Application of both retrospective (n = 8) and prospective (n = 3) compressed sensing methods demonstrated that 1.8× acceleration had negligible impact on qualitative image appearance, with no statistically significant change in measured lung ventilated volume. Acceleration factors of 2.4× and 3.0× resulted in increasing differences between fully sampled and undersampled datasets. CONCLUSION: This study demonstrates methods for determining optimal acquisition parameters for 19 F-MRI of inhaled perfluoropropane and shows significant reduction in scan acquisition times (and thus participant breath hold duration) by use of compressed sensing.

Perfluorocarbons for the treatment of decompression illness: how to bridge the gap between theory and practice.

Decompression illness (DCI) is a complex clinical syndrome caused by supersaturation of respiratory gases in blood and tissues after abrupt reduction in ambient pressure. The resulting formation of gas bubbles combined with pulmonary barotrauma leads to venous and arterial gas embolism. Severity of DCI depends on the degree of direct tissue damage caused by growing bubbles or indirect cell injury by impaired oxygen transport, coagulopathy, endothelial dysfunction, and subsequent inflammatory processes. The standard therapy of DCI requires expensive and not ubiquitously accessible hyperbaric chambers, so there is an ongoing search for alternatives. In theory, perfluorocarbons (PFC) are ideal non-recompressive therapeutics, characterized by high solubility of gases. A dual mechanism allows capturing of excess nitrogen and delivery of additional oxygen. Since the 1980s, numerous animal studies have proven significant benefits concerning survival and reduction in DCI symptoms by intravenous application of emulsion-based PFC preparations. However, limited shelf-life, extended organ retention and severe side effects have prevented approval for human usage by regulatory authorities. These negative characteristics are mainly due to emulsifiers, which provide compatibility of PFC to the aqueous medium blood. The encapsulation of PFC with amphiphilic biopolymers, such as albumin, offers a new option to achieve the required biocompatibility avoiding toxic emulsifiers. Recent studies with PFC nanocapsules, which can also be used as artificial oxygen carriers, show promising results. This review summarizes the current state of research concerning DCI pathology and the therapeutic use of PFC including the new generation of non-emulsified formulations based on nanocapsules.

Brain oxygenation with a non-vasoactive perfluorocarbon emulsion in a rat model of traumatic brain injury.

OBJECTIVE: The aim of this study was to assess, in two experiments, the safety and efficacy of the PFC emulsion Oxycyte as an oxygen therapeutic for TBI to test the hypothesis that early administration of this oxygen-carrying fluid post-TBI would improve brain tissue oxygenation (Pbt O2 ). METHODS: The first experiment assessed the effects of Oxycyte on cerebral vasoactivity in healthy, uninjured rats using intravital microscopy. The second experiment investigated the effect of Oxycyte on cerebral Pbt O2 using the PQM in TBI model. Animals in the Oxycyte group received a single injection of Oxycyte (6 mL/kg) shortly after TBI, while NON animals received no treatment. RESULTS: Oxycyte did not cause vasoconstriction in small- (<50 µm) or medium- (50-100 µm) sized pial arterioles nor did it cause a significant change in blood pressure. Treatment with Oxycyte while breathing 100% O2 did not improve Pbt O2 . However, in rats ventilated with ~40% O2 , Pbt O2 improved to near pre-TBI values within 105 minutes after Oxycyte injection. CONCLUSIONS: Although Oxycyte did not cause cerebral vasoconstriction, its use at the dose tested while breathing 100% O2 did not improve Pbt O2 following TBI. However, Oxycyte treatment while breathing a lower enriched oxygen concentration may improve Pbt O2 after TBI.

Intrinsically absorbing photoacoustic and ultrasound contrast agents for cancer therapy and imaging.

Nanoparticles are submicrometer in size and are used in a variety of ways in the biomedical field. They can carry therapeutic drugs, either in the particle core or surface to target cancer sites in the body. Additionally they can contain imaging agents to diagnose and monitor the tumor size using different imaging modalities, such as fluorescence and nuclear magnetic resonance imaging. Novel theranostic nanoparticle agents, called perfluorohexane nanoemulsions (PFH-NEs) were synthesized whose intrinsic properties could be used for both imaging (ultrasound and photoacoustic) and therapy. Compared to other theranostic agents, our PFH-NEs can absorb sufficient near-infrared light to enhance contrast and provide deeper penetration imaging at laser fluences causing minimal damage to healthy tissue. One contrast mechanism (optical absorption/photoacoustics) allows us to validate localization of the agent and another (acoustic impedance/ultrasound) allows the imaging of therapeutic delivery after particle activation. In this work, we show the potential of these PFH-NEs to be used as multimodal imaging agents and for therapy.

Enhanced photodynamic therapy by encapsulation of perfluorocarbon into PEGylated near-infared dyes.

Near-Infrared (NIR) dyes, with improved tissue penetration, minimal invasiveness and high specificity, have gained great interests in diagnosing and treating tumors. However, the poor solubility in aqueous medium and low 1O2 quantum yields of NIR dyes restrict their application in PDT (photodynamic therapy) research. Herein, a novel nanosystem with modifying the NIR dyes and encapsulating perfluorocarbon is reported for improving the PDT effectiveness of NIR dyes. By adding the PEG2000-SH and the C13 carbon chain to a NIR representative dye IR780, the new formed material PEG-IR780-C13 shows good solubility in water. Then PFTBA was encapsulated into PEG-IR780-C13 to form a nanosystem (PFTBA@PEG-IR780-C13). When exposed to laser irradiation, the nanosystem showed enhanced production of 1O2 and significantly increased PDT both in vivo and in vitro. Therefore, this work provides an approach for design and application of NIR dyes.

Liver graft preservation using perfluorocarbon improves the outcomes of simulated donation after cardiac death liver transplantation in rats.

The outcomes of liver transplantation (LT) from donation after cardiac death (DCD) donors remain poor due to severe warm ischemia injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD LT was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia/reperfusion injury (IRI) and survival after DCD LT was investigated. Orthotopic liver transplants were performed in male Lewis rats, using DCD liver grafts preserved with cold University of Wisconsin (UW) solution in the control group and preserved with cold oxygenated UW solution with addition of 20% PFC in the PFC group. For experiment I, in a 30-minute donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. For experiment II, in a 50-minute donor warm ischemia model, the postoperative survival was assessed. For experiment I, the levels of serum aspartate aminotransferase, alanine aminotransferase, hyaluronic acid, malondialdehyde, and several inflammatory cytokines were significantly lower in the PFC group. The hepatic expression levels of tumor necrosis factor α and interleukin 6 were significantly lower, and the expression level of heme oxygenase 1 was significantly higher in the PFC group. Histological analysis showed significantly less necrosis and apoptosis in the PFC group. Sinusoidal endothelial cells and microvilli of the bile canaliculi were well preserved in the PFC group. For experiment II, the postoperative survival rate was significantly improved in the PFC group. In conclusion, graft preservation with PFC attenuated liver IRI and improved postoperative survival. This graft preservation protocol might be a new therapeutic option to improve the outcomes of DCD LT. Liver Transplantation 23 1171-1185 2017 AASLD.

Treatment of Myopic Foveoschisis with Air Versus Perfluoropropane: A Retrospective Study.

BACKGROUND The aim of this study was to compare the efficacy of air and perfluoropropane (C3F8) combined with vitrectomy to treat myopic foveoschisis (MF). MATERIAL AND METHODS A retrospective comparison of a consecutive series of surgical patients was performed. Ninety-seven eyes of 91 patients with MF were assigned to undergo 23G vitrectomy. After internal limiting membrane (ILM) peeling, the vitreous cavity was filled with air in 48 eyes of 45 patients (Air Group). Fluid-air exchange was performed in 49 eyes of 46 patients (C3F8 Group) followed by an injection of 14% C3F8. Patients were evaluated using best-corrected visual acuity (BCVA) and optical coherence tomography. RESULTS Preoperatively, there was no significant difference in clinical features between the groups. After surgery, BCVA was markedly improved and the foveoschisis height was reduced in both groups compared with baseline (P<0.01), but the difference between the groups was not significant (P>0.05). No significant differences were noted in BCVA improvement and retinal restoration (P=0.33 and 0.39, respectively) in the mild and moderate subgroups (foveoschisis height ≤400 µm) between the tamponades. However, in the severe group (foveoschisis height >400 µm), C3F8 had a more favorable cure rate and foveoschisis height reduction improvement compared with air (P=0.04 and 0.04, respectively) at the last visit. CONCLUSIONS Vitrectomy combined with ILM peeling is effective in the treatment of myopic foveoschisis, and the choice of tamponade depends on the severity of foveoschisis. Air can be used for patients with a foveoschisis height ≤400 µm, but C3F8 is more effective for patients with a foveoschisis height >400 µm.

Evaluation of a new topical skin protectant (RD1433) for the prevention and treatment of incontinence-associated dermatitis.

Context Incontinence-associated dermatitis (IAD) is a type of moisture-associated dermatitis caused by repeated skin exposure to urine or stool. A product that could mitigate such symptoms would have a significant impact on cost of care and patients' quality of life. Objective This study compared the clinical efficacy of RD1433 and a comparator product (Vaseline®) in preventing and treating experimental IAD skin lesions. Materials and methods For the "prevention" part of the study, skin sites in eight human volunteers were treated daily for 5 d with either RD1433 or Vaseline® immediately prior to synthetic urine exposure. In the "treatment" part, exposure to synthetic urine was substituted for Vaseline® or RD1433 application on the first 2 d to promote the development of skin lesions prior to the application of the products from day three. Product efficacy was quantified by visual scoring and an array of biophysical instruments. Results Both RD1433 and Vaseline® significantly reduced lesion progression when applied as a prophylactic. When applied as a treatment (following establishment of skin lesions), RD1433 demonstrated a statistically significant improvement in several measures of skin function whereas there was no statistically significant improvement following treatment with Vaseline®. Conclusions The findings of this study suggest that RD1433 may be superior to Vaseline® in the prevention and treatment of experimental IAD lesions. Clearly, further work is required to establish the efficacy of RD1433 with patients in a clinical environment.

Perfluorocarbon emulsion therapy attenuates pneumococcal infection in sickle cell mice.

Impaired immunity and tissue hypoxia-ischemia are strongly linked with Streptococcus pneumoniae pathogenesis in patients with sickle cell anemia. Perfluorocarbon emulsions (PFCEs) have high O2-dissolving capacity and can alleviate tissue hypoxia. Here, we evaluate the effects of intravenous PFCE therapy in transgenic sickle cell (HbSS) mice infected with S. pneumoniae. HbSS and C57BL/6 (control) mice intravenously infected with S. pneumoniae were treated intravenously with PFCE or phosphate-buffered saline (PBS) and then managed in either air/O2 (FiO2 proportion, 50%; hereafter referred to as the PFCE-O2 and PBS-O2 groups) or air only (hereafter, the PFCE-air and PBS-air groups) gas mixtures. Lungs were processed for leukocyte and bacterial counts and cytokine measurements. HbSS mice developed severe pneumococcal infection significantly faster than C57BL/6 mice (Kaplan-Maier analysis, P < .05). PFCE-O2-treated HbSS mice had significantly better survival at 72 hours than HBSS mice treated with PFCE-air, PBS-O2, or PBS-air (P < .05). PFCE-O2-treated HbSS mice also had significantly lower pulmonary leukocyte counts, lower interleukin 1ß and interferon γ levels, and higher interleukin 10 levels than PFCE-air-treated HbSS mice. Clearance of S. pneumoniae from lungs of HbSS mice or C57BL/6 mice was not altered by PFCE treatment. Improved survival of PFCE-O2-treated HbSS mice infected with S. pneumoniae is associated with altered pulmonary inflammation but not enhanced bacterial clearance.

Hextend-perfluorocarbon cocktail inhibits mean arterial pressure response in a rabbit shock model.

BACKGROUND: Hextend (HEX) is standard of care resuscitation fluid for combat-related traumatic hemorrhage. Because HEX has limited oxygen-carrying capacity, combination therapy with oxygen therapeutics could improve oxygen delivery after hemodynamic shock. We hypothesized that addition of perfluorocarbon (PFC) to HEX would improve hemodynamics and oxygen delivery marker response in a rabbit model of hemorrhagic shock. METHODS: Anesthetized New Zealand rabbits (n = 23) were randomly allocated to resuscitation with fresh whole blood (FWB), HEX, or HEX plus PFC (HEX + PFC) after 60 min of hemorrhagic hypotension. Mean arterial pressure (MAP) was sampled every 2-3 min for 120 min postinfusion; MAP profiles were modeled by a one-compartment pharmacokinetic model to determine peak MAP (Pmax), time to peak MAP (tmax), and postinfusion MAP persistence. Arterial blood was sampled every 15 min to examine pH, blood gases PO2 and pCO2, metabolites lactate and glucose, methemoglobin (metHb), and electrolytes. RESULTS: Compared with FWB and HEX, HEX + PFC administration resulted in delayed peak MAP and less persistent (P < 0.0001) MAP elevation; metHb was significantly elevated (P < 0.0001) compared with FWB and HEX. There were no significant differences in PO2, pCO2, or pH. Glucose, hematocrit, and hemoglobin of both HEX and HEX + PFC were significantly lower relative to FWB. Lactate clearance was modest and transient for all treatments; base deficit was significantly more negative for HEX + PFC. CONCLUSIONS: Addition of PFC to HEX did not improve hemodynamics or acidosis. Further dose- and volume-range studies are required to test efficacy of PFC in combination with HEX for hemorrhagic shock.

Clinical management of vitreomacular traction.

PURPOSE OF REVIEW: To describe recent evidence regarding the clinical management of vitreomacular traction (VMT). RECENT FINDINGS: Recent studies have reported favorable outcomes in patients with VMT managed with observation, pharmacologic vitreolysis with ocriplasmin, and intravitreal perfluoropropane gas. Subgroup analysis has identified features associated with spontaneous release of VMT as well as features associated with successful pharmacologic release of VMT with ocriplasmin. SUMMARY: Observation may be an appropriate initial recommendation for patients with mild VMT. When treatment is necessary, pharmacologic vitreolysis with ocriplasmin is an effective nonsurgical therapeutic option. Careful patient selection improves success rates with ocriplasmin. Further study is necessary to establish the efficacy of intravitreal perfluoropropane gas for VMT as well as the efficacy of ocriplasmin in patients with VMT and concurrent retinal disease. As these treatments are more widely used, prospective data will continue to clarify their risk/benefit profile.

The Role of Contrast-enhanced Ultrasound in Guiding Radiofrequency Ablation of Hepatocellular Carcinoma: A Retrospective Study.

PURPOSE: The objective of the study was to determine the efficacy of contrast-enhanced ultrasound (CEUS) using ultrasound (US)-specific microbubbles in guiding radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). METHODS: A retrospective analysis of 50 patients with HCC treated with CEUS guided RFA using perflutren at our institution was performed. CEUS images were first compared to B-mode US images performed at the same RFA session to determine the ability of CEUS to increase the conspicuity of lesions. A qualitative score (1 = poor, 2 = fair, 3 = excellent) was used to grade the ability to visualize the lesions. The preprocedure CEUS images were then evaluated using the most recent prior contrast enhanced computed tomography (CT) or magnetic resonance imaging (MRI). The efficacy of the treatment was evaluated with short-term follow-up imaging (median 1 month) for presence of residual or recurrent disease. RESULTS: CEUS allows at least fair visualization (score ≥2) in 78% (reader 1) and 80% (reader 2) of the lesions not visualized by B-mode US, and 50% (reader 1) and 42% (reader 2) of the lesions poorly visualized by B-mode US. Lesion appearances on CEUS are largely concordant with those on CT or MRI: 88% for reader 1, 96% for reader 2. With CEUS-guided RFA, complete response was achieved in the vast majority of the lesions at short-term follow-up: 82% for reader 1, 94% for reader 2. CONCLUSIONS: CEUS increases the conspicuity and provides better characterization of hypervascular HCC that are either not seen or poorly seen on B-mode US, and CEUS provides real-time guidance of RFA with good short-term treatment responses.

Development and initial experience with a colored perfluorocarbon liquid for intraocular tamponade in vitreoretinal surgery.

PURPOSE: To present the development and initial experience of a novel colored perfluorocarbon liquid (PFCL) in vitreoretinal surgery. METHODS: This was an experimental laboratory study and prospective human interventional study. F6H8 (Fluoron GmbH) was colored by adding 0.3 g/L blue anthraquinone dye. Subsequently, 20% colored F6H8 was prepared by mixing with perfluorooctane or perfluorodecalin (Fluoron GmbH). The novel product is not yet FDA approved for human application. In the laboratory, the colored PFCL was covered with 1) uncolored PFCL, 2) BSS, and 3) silicone oil. Cell toxicity was evaluated in L929 mouse fibroblasts using a growth inhibition assay. Porcine ex vivo eyes were evaluated after vitrectomy followed by intravitreal and subretinal colored PFCL infusion. A pilot, prospective, noncomparative interventional study was conducted in patients with retinal detachment with proliferative vitreoretinopathy (PVR). RESULTS: The density of the colored PFLC mixture was 1.664 g/cm for perfluorooctane and 1.802 g/cm for perfluorodecalin. There was no relevant cell growth inhibition with any concentration of colored PFCL tested. Experiments in pigs revealed that infusion of the colored PFCL caused neither staining of the internal limiting membrane nor intravitreal residual droplets. In the prospective study, 9 eyes (75%) underwent surgery for rhegmatogenous retinal detachment with at least grade C PVR. The colored PFCL enabled retinal break examination and detection of residual intravitreal droplets in all surgeries. There was no case of separation or leakage of the dye from the PFCL solution that could have caused unwanted staining of the vitreous or epiretinal surface. CONCLUSION: The colored PFCL enabled intraoperative maneuvers such as endolaser use. In addition, removal of the colored PFCL was easily achieved at the end of surgery.

Treatment of micro air bubbles in rat adipose tissue at 25 kPa altitude exposures with perfluorocarbon emulsions and nitric oxide.

INTRODUCTION: Perfluorocarbon emulsions (PFC) and nitric oxide (NO) releasing agents have on experimental basis demonstrated therapeutic properties in treating and preventing the formation of venous gas embolism as well as increased survival rate during decompression sickness from diving. The effect is ascribed to an increased solubility and transport capacity of respiratory gases in the PFC emulsion and possibly enhanced nitrogen washout through NO-increased blood flow rate and/or the removal of endothelial micro bubble nuclei precursors. Previous reports have shown that metabolic gases (i.e., oxygen in particular) and water vapor contribute to bubble growth and stabilization during altitude exposures. Accordingly, we hypothesize that the administration of PFC and NO donors upon hypobaric pressure exposures either (1) enhance the bubble disappearance rate through faster desaturation of nitrogen, or in contrast (2) promote bubble growth and stabilization through an increased oxygen supply. METHODS: In anesthetized rats, micro air bubbles (containing 79% nitrogen) of 4-500 nl were injected into exposed abdominal adipose tissue. Rats were decompressed in 36 min to 25 kPa (~10,376 m above sea level) and bubbles studied for 210 min during continued oxygen breathing (FIO2 = 1). Rats were administered PFC, NO, or combined PFC and NO. RESULTS: In all groups, most bubbles grew transiently, followed by a stabilization phase. There were no differences in the overall bubble growth or decay between groups or when compared with previous data during oxygen breathing alone at 25 kPa. CONCLUSION: During extreme altitude exposures, the contribution of metabolic gases to bubble growth compromises the therapeutic effects of PFC and NO, but PFC and NO do not induce additional bubble growth.