α-Fe2O3@Au-PEG-Ce6-Gd Nanoparticles as Acidic H2O2-Driven Oxygenators for Multimodal Imaging and Synergistic Tumor Therapy.

Nanoparticles with visual imaging capabilities and synergistic therapeutics have a bright future in antitumor applications. However, most of the current nanomaterials lack multiple imaging-guided therapeutic capabilities. In this study, a novel enhanced photothermal photodynamic antitumor nanoplatform with photothermal imaging, fluorescence (FL) imaging, and MRI-guided therapeutic capabilities was constructed by grafting gold, dihydroporphyrin Ce6, and Gd onto α-iron trioxide. This antitumor nanoplatform can convert NIR light into local hyperthermia at a temperature of up to 53 °C under NIR light irradiation, while Ce6 can generate singlet oxygen, which further synergizes the tumor-killing effect. At the same time, α-Fe2O3@Au-PEG-Ce6-Gd can also have significant photothermal imaging effect under light irradiation, which can guide to see the temperature change near the tumor tissue. It is worth noting that α-Fe2O3@Au-PEG-Ce6-Gd can have obvious MRI and FL imaging effects after tail vein injection in mice with blood circulation, realizing imaging-guided synergistic antitumor therapy. α-Fe2O3@Au-PEG-Ce6-Gd NPs provide a new solution for tumor imaging and treatment.

Oxygenated kidney preservation techniques.

Improving preservation techniques to minimize injury is of particular importance in organs from marginal donors. Since the introduction of transplantation and routine use of hypothermic temperatures for kidney preservation, there has been much debate on whether it is necessary to add oxygen to support the low level of metabolism under these conditions. Supplementing the kidney with oxygen during hypothermic preservation is not common practice. However, there is evidence to support its application. Oxygen can be added by various techniques such as retrograde persufflation whereby filtered and humidified oxygen is bubbled through the vasculature; under hyperbaric conditions using specialized pressurized chambers; during hypothermic machine perfusion; with the addition of oxygen carriers; and under normothermic conditions. Evidence suggests that oxygenation is particularly beneficial in restoring cellular levels of adenosine triphosphate after kidneys have been subjected to warm or cold ischemic injury. However, under normal conditions, the benefits are less convincing, but the evidence is insufficient to draw any conclusions. This overview explores the ways in which oxygen can be administered during preservation in experimental and clinical models of kidney transplantation.

Efficacy of a new oxygenator-integrated fat and leukocyte removal device.

We evaluated the effectiveness of a new oxygenator-integrated device for removing lipid particles and leukocytes from shed mediastinal blood in 20 patients undergoing elective cardiac surgery under cardiopulmonary bypass. Another 20 patients undergoing cardiac surgery without the device served as controls. After filtration with the RemoveLL device, lipid particles, leukocytes, and fats were significantly reduced compared to preoperative levels. In the control group, blood fats and lipid particles at the end of cardiopulmonary bypass were significantly increased compared to preoperative levels. Leukocyte counts at the end of bypass were significantly lower in patients who had the filtration device compared to the control group. Platelets counts and hematocrit changes were not significantly different between the 2 groups.

An evaluation of the safety and efficacy of an anti-inflammatory, pulmonary enteral formula in the treatment of pediatric burn patients with respiratory failure.

Respiratory failure is associated with a high mortality rate in burned children. Recently, a specialized pulmonary enteral formula (SPEF) was commercially introduced as an adjunct intervention in acute lung injury management. SPEF contains condition-specific nutrients to modulate the inflammatory response. The study examined SPEF impact in critically ill, pediatric burn patients with respiratory failure. Medical records of acute burn patients admitted December 1997 to October 2006 were reviewed for SPEF treatment. Respiratory and renal indices were compared on the first and final days of SPEF use. Nineteen patients with respiratory failure received SPEF for a mean of 10.8 +/- 0.9 days during their acute burn course. Mean age was 5.3 +/- 1.5 years. Mean total body surface area burn was 44.3 +/- 5.4% with 32.5 +/- 6.4% full thickness. Patients were admitted 2.3 +/- 0.9 days postburn. Significant improvements in peak pressure, PEEP, FiO2, P:F ratio, Pco2, Po2, and ETco2 were noted. Seventeen of the 19 patients survived despite the fact that 9 of the 19 patients developed severe barotrauma requiring multiple tube thoracotomies, and all 19 had extremely poor prognoses at SPEF initiation. Adult SPEF formula for critically ill, pediatric burn patients with respiratory failure is safe and well tolerated. SPEF seems to facilitate recovery from acute lung injury as evidenced by improvements in oxygenation and pulmonary compliance.

Hemolysis in cardiac surgery patients undergoing cardiopulmonary bypass: a review in search of a treatment algorithm.

Hemolysis is a fact in all extracorporeal circuits, as shown in various studies by the increasing levels of plasma-free hemoglobin (PfHb) and decreasing levels of haptoglobin during and after cardiopulmonary bypass (CPB). Beside complete red blood cell (RBC) destruction or hemolysis, RBCs can also be damaged on a sublethal level, resulting in altered rheological properties. Increased levels of free RBC constituents together with an exhaust of their scavengers result in a variety of serious clinical sequela, such as increased systemic and pulmonary vascular resistance, altered coagulation profile, platelet dysfunction, renal tubular damage, and increased mortality. Sublethal RBC damage is characterized by decreased microperfusion and hypoxic RBCs, leading to end organ dysfunction caused by cellular ischemia. Isolated extracorporeal circuit components can be considered non-hemolytic if used according to recommendations, but extracorporeal circuit composition and management during CPB can still be optimized, avoiding cell damaging mechanical forces. Although most RBC destruction in standard CPB remains within the capacity of the endogenous clearing mechanisms, in some cases, levels of PfHb do substantially rise, and precautionary measures need to be taken. Higher degree of hemolysis can be expected in young children, after extensive surgery, and in prolonged support as in patients supported by ventricular assist devices (VADs) or extracorporeal membrane oxygenation (ECMO). These patients are especially susceptible to the toxic influences of unscavenged RBC constituents and the loss of rheologic properties of the RBCs. Considering the high percentage of neurologic and renal sequela in post-cardiotomy patients, all imbalances possibly contributing to these morbidities should be focused on and prevented, if not treated. Considering the severity of the consequences of RBC damage, the high incidence of this complication, and especially the lack of interventional strategies in cases of suspected or confirmed RBC damage, there may be a need for a treatment algorithm for this phenomenon.

An innovative simple technique of blood conservation in adult patients with tetralogy of Fallot and severely raised hemoglobin.

The adult patients of tetralogy of Fallot often present with high hemoglobin levels. High hemoglobin and hematocrit on cardiopulmonary bypass (CPB) are associated with increased hemolysis, plasma free hemoglobin, renal dysfunction or failure, postoperative bleeding, exploration for bleeding, and increased requirement of allogeneic blood and blood products. Despite the presence of high hemoglobin and its association with adverse outcome, blood conservation is rarely practiced in these patients because of the fear of possible hemodynamic instability, and hypoxemic spell. We describe an innovative, simple technique of blood conservation for adult patients of tetralogy of Fallot with severely raised hemoglobin. With this technique, hemoglobin can be normalized on CPB; moreover, there is no fear of hypoxemic spell or hemodynamic instability. Furthermore, the blood conserved is readily available for transfusion in the perioperative period, if needed.

Preparing to perform an awake fiberoptic intubation.

Fiberoptically guided tracheal intubation represents one of the most important advances in airway management to occur in the past thirty years. Perhaps its most important role is in management of the anticipated difficult airway. This is a situation in which the dangers of encountering the life-threatening "can't intubate, can't ventilate" situation can be avoided by placement of an endotracheal tube while the patient is awake. Although skill at the procedure of endoscopy is obviously necessary in this setting, these authors hold that success or failure of the technique frequently depends on the adequacy of preparation. These measures include 1) pre-operative assessment of the patient; 2) careful explanation of what lies in store; 3) "setting the stage"; 4) preparing the equipment to be used; and 5) preparing the patient (antisialogue, sedation, application of topical anesthesia to the upper airway). If these preparatory measures are carried out meticulously, the likelihood of performing a successful and comfortable awake fiberoptic tracheal intubation is greatly increased.

Isolated lung perfusion with tumor necrosis factor for pulmonary metastases.

BACKGROUND: A phase I trial was initiated to define the feasibility and safety of single-lung isolation perfusion with tumor necrosis factor-alpha, interferon-gamma, and moderate hyperthermia for patients with unresectable pulmonary metastases. METHODS: Twenty patients with lung metastases (Ewing's, 2; sarcoma, 8; melanoma, 6; other, 4) were considered for single-lung isolation perfusion with 0.3 to 6.0 mg of tumor necrosis factor-alpha and 0.2 mg interferon-gamma delivered through an oxygenated pump circuit. Sixteen perfusions were performed in 15 patients (bilateral in 1). Metastases were completely resected (no single-lung isolation perfusion) in 3 patients, 1 patient had extrapulmonary disease, and one single-lung isolation perfusion was aborted for mechanical reasons. RESULTS: There were no significant changes in systemic arterial blood pressure or cardiac output during perfusion. Systolic pulmonary artery pressure increased with isolation, but returned to pre-single-lung isolation perfusion levels after clamp release. The maximum systemic tumor necrosis factor-alpha level was 8 ng/mL, whereas pump-circuit levels ranged from 200 to 10,976 ng/mL. There were no deaths, and the mean hospitalization period was 9 days (range, 5 to 34 days). A short-term (6 to 9 month) unilateral decrease in perfused nodules was noted in 3 patients (melanoma in 1, adenoid cystic carcinoma in 1, renal cell carcinoma in 1). CONCLUSIONS: Future studies using a combination of biologic modifiers, chemotherapy, and hyperthermia should be pursued to define active cytotoxic agents that will preserve underlying pulmonary function.

Effectiveness of intraoperative autologous whole blood and platelet-rich plasma in cardiac surgery.

Autologous whole blood and platelet-rich plasma harvested intraoperatively before cardiopulmonary bypass have been used by many in an effort to reduce the use of allogeneic blood transfusions during cardiac surgery. This brief review analyses the literature published concerning those two techniques. Although theoretically appealing, neither technique appears at present to withstand close scrutiny because of limitations in the design of many clinical studies. Efforts at blood transfusion avoidance during cardiac surgery may be best directed toward the salvage of intraoperative blood (including the residual oxygenator circuit contents), selective acceptance of low haemoglobin concentrations, and prophylactic administration of antifibrinolytic drugs.

Clinical significance of heparin in the residual pump oxygenator blood, reinfused postoperatively after cardiopulmonary bypass.

Postcardiopulmonary bypass (CPB) heparin levels and thrombin time were measured in 20 patients following routine open cardiac operations. There was a statistically significant increase in heparin concentration and thrombin time ratio on completion of transfusion of the residual pump oxygenator blood. An hour after the end of the transfusion there was no statistically significant difference in the heparin concentration and thrombin time ratio compared to values before and immediately after transfusion. We also observed a significant decrease in the chest drainage over a period of four hours which was unrelated to plasma heparin level. Measurements of thrombin time in the post bypass period closely follow plasma heparin levels. If postoperative bleeding arose it was due to inadequate surgical haemostasis or coagulation defect other than residual heparinization. Thus this confirms further that heparin is not the sole aetiological factor in postoperative bleeding post-CPB.

[Results of the Berlin HOT/UVB comparative study in patients with peripheral arterial occlusive disorders]. / Ergebnisse der Berliner HOT/UVB-Vergleichstudie bei Patienten mit peripheren arteriellen Durchblutungsstörungen.

Both photobiological methods haematogenic oxydation therapy (HOT) and therapy by retransfused ultraviolet irradiated own blood (UVB) were compared with regard to its therapeutic efficacy in patients with peripheral arterial occulusive disease of lower extremities in stage II by Fontaine. In parallel to paraclinical and coagulation data, haemodynamic as well as haemorheological parameters were investigated to clarify possible mechanisms of action of these therapies. 15 male patients were enclosed in the corresponding patients groups with a mean walking distance of 178 +/- 108 m (HOT) and 213 +/- 147 m (UVI), respectively. The claudicatio-distances were significantly improved after 10 series of therapy by 94% in the HOT-group and by 83% in the UVI-group, respectively. A significant difference in the improvement of walking distances could not be detected between both therapeutical methods. Significant alterations in observed paraclinical parameters were not observed.

Transfusion therapy in cardiac surgery: impact of the Paul Gann Blood Safety Act in California.

The Paul Gann Blood Safety Act became law in California on January 1, 1990, mandating that patients be informed of the risks and alternatives of blood transfusions. To evaluate the impact of this legislation, the authors compared transfusion therapy in patients undergoing cardiac surgery during 1990 to previous years (1986 to 1987 and 1989). Surgical techniques were unchanged. Homologous component usage was 8.7 +/- 0.6 (mean +/- SE) units/patient in 1986 to 1987 (n = 373), 8.2 +/- 0.9 in 1989 (n = 219) and 4.3 +/- 0.6 in 1990 (n = 222), P less than .001 by ANOVA. Erythrocyte transfusions were 3.5 +/- 0.2, 3.2 +/- 0.2, and 2.2 +/- 0.2 units/patient (P less than .001); platelet/plasma usage was 5.2 +/- 0.5, 4.9 +/- 0.7 and 2.1 +/- 0.4 units/patient (P less than .001). The number of patients not requiring transfusions increased from 28 per cent in 1989 (61 of 219) to 47 per cent in 1990 (104 of 222). A slight but significant decrease in cardiopulmonary bypass time and perioperative blood loss occurred. The authors conclude that this legislation stimulated the surgical team to control blood loss during surgery and to avoid the anticipatory use of component transfusions.

[In vitro and clinical study of complement activation during cardiopulmonary bypass with reference to types of oxygenator, primed autologous blood and patient's factor].

Complement activation during cardiopulmonary bypass (CPB) was studied in vitro and in vivo with regard to types of oxygenator, primed autologous blood and patient's factor. In vitro study was performed using human blood in a simple circuit involving an oxygenator, roller pump and connector tubing. In vivo study was carried out in 118 patients and divided into bubble (BO) and membrane oxygenator (MO) groups. The influence of primed homologous to circulating autologous blood volume (H/A) ratio was also examined. In vitro study, C3a and C4a increased steeply in the BO group. On the other hand, in the MO group, C3a and C4a increased up to minute of 60, and afterwards gradually decreased. In clinical study, complement was more activated in the BO group than in the MO group. These results supported that in the BO group, immunoglobulin denatured by blood-gas interface played an important role in complement activation. In membrane oxygenator, blood-material interface was a major cause of complement activation. In order to reduce these complement activation, we introduced fresh concentrated red cells, which was almost free of immunoglobulin, as a primed blood. Application of this method in clinical study, complement activation was reduced and postoperative lung function was improved significantly. These changes were more significant in the BO group. In the high H/A group, differences of anaphylatoxin level between BO and MO group had a tendency to increase. This method is useful to the CPB case of neonate and infant, which was subjected to be primed with a large amount of blood.

Hyperthermic regional perfusion using membrane- instead of bubble-oxygenators. An experimental and clinical study.

To achieve adequate tissue perfusion during hyperthermic regional perfusion, perfusion pressures should be maintained at near normal mean systemic arterial pressures. During experimental as well as during clinical perfusions however, unphysiologically high perfusion flows were needed to keep the perfusion pressure at the desired level. Since both high perfusion flows and high perfusion pressures have been associated with the post-operative complications such as severe edema and tissue damage, as well as with an increased leakage of perfusate to the systemic circulation, low perfusion flows have been used in regional perfusion. High perfusion flows in our previous experimental studies were attributable to a marked reduction in vascular resistance. This decrease is believed to be caused by the release of vasodilatory constituents of damaged blood cells, and it is the extra-corporeal circuit, and in particular the bubble-oxygenator that is thought to be responsible. The superior haemocompatibility of membrane-oxygenators over bubble-oxygenators has been established in cardio-pulmonary bypass. We compared the use of a membrane-oxygenator with that of a bubble-oxygenator in regional perfusion to see if more normal haemodynamics could be maintained and vasodilatation prevented. In the experimental as well as in the clinical perfusions the use of a bubble-oxygenator required unphysiologically high perfusion flows to maintain the perfusion pressure at the level required to obtain an adequate microcirculation. In contrast the use of a membrane-oxygenator permitted a nearly physiological perfusion flow to maintain an adequate perfusion pressure as well as an adequate micro-circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

A new technique for hemodilution, preparation of autologous platelet-rich plasma and intraoperative blood salvage in cardiac surgery.

We have developed a new system for the production of autologous platelet-rich plasma and red blood cell concentrates to be used in autologous transfusion support of cardiac surgery patients. In 15 operations no homologous blood products were required. Costs were diminished since with the same harness it was possible to carry out the intraoperative blood salvage and concentrate the erythrocytes contained in the oxygenator and its lines. Indirect costs were also reduced since no infective complication was observed due to homologous blood products.

Massive arterial air embolism due to rupture of pulsatile assist device: successful treatment in the hyperbaric chamber.

We present the case of a patient who had rupture of a pulsatile assist device (PAD) accompanied by massive air embolism, and the treatment that brought it to a successful outcome. After rupture of the skin of the PAD balloon, a massive amount of air was injected into the ascending aorta. The patient was placed in Trendelenburg position and cooled in deep hypothermia with cardiopulmonary bypass. He was given 1 gm of methylprednisolone intravenously, and the aortic valve replacement and double vein bypass graft were performed. After completion of the operation, the patient was partially rewarmed to 30 degrees C central temperature and transported by ambulance to a hyperbaric chamber where he was compressed to 6 atmospheres absolute 9 hours after the accident with clinical signs of severe brain dysfunction. The patient recovered completely and was discharged from the hospital on the tenth postoperative day.