Evaluation of antiplasmodial activity and cytotoxicity assays of amino acids functionalized magnetite nanoparticles: Hyperthermia and flow cytometry applications.

We report the synthesis of magnetite nanoparticles (MNP) and their functionalization with glycine (MNPGly), ß-alanine (MNPAla), L-phenylalanine (MNPPhAla), D-(-)-α-phenylglycine (MNPPhGly) amino acids. The functionalized nanoparticles were characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), electron paramagnetic resonance (EPR), vibrating sample magnetometry (VSM), Mössbauer spectroscopy (MS), magnetic hyperthermia (MH), dynamic light scattering and zeta potential. The functionalized nanoparticles had isoelectric points (IEP) at pH ≃ 4.4, 5.8, 5.9 and 6.8 for samples MNPGly, MNPAla, MNPPhGly and MNPPhAla, respectively, while pure magnetite had an IEP at pH 5.6. In the MH experiments, the samples showed specific absorption rate (SAR) of 64, 71, 74, 81 and 66 W/g for MNP, MNPGly, MNPAla, MNPPhGly, and MNPPhAla, respectively. We used a flow cytometric technique to determine the cellular magnetic nanoparticles plus amino acids content. Magnetic fractionation and characterization of Resovist® magnetic nanoparticles were performed for applications in magnetic particle imaging (MPI). We have also studied the antiproliferative and antiparasitic effects of functionalized MNPs. Overall, the data showed that the functionalized nanoparticles have great potential for using as environmental, antitumor, antiparasitic agents and clinical applications.

Synthesis and colloidal characterization of folic acid-modified PEG-b-PCL Micelles for methotrexate delivery.

Hydrophobic drugs, such as methotrexate, are not easily delivered into the human body. Therefore, the use of amphiphilic nanoplatforms to the transport of these drugs through the bloodstream is a challenge. While the hydrophobic region interacts with the drug, the hydrophilic outer layer enhances its bioavailability and circulation time. Poly (ethylene glycol)-block-poly(ε-caprolactone) PEG-b-PCL micelles are biodegradable and biocompatible, allowing its use as a nanocarrier for drug delivery systems. The stealth property of PEG that composes the outer layer of nanoplatforms, makes the micelle unperceivable to phagocytic cells, increasing the circulation time in the human body. In addition, folic acid functionalization enables micelle selectively targeting to cancer cells, improving treatment efficiency and reducing side effects. In this work, PEG-b-PCL copolymer was synthesized by ring opening polymerization (ROP) of the ε-caprolactone with Poly(ethylene glycol) as a macroinitiator and tin(II) 2-ethyl hexanoate as a catalyst. Functionalization of such micelles with folic acid occurred through the modification of the PEG terminal group. The surface modification of the copolymer micelles resulted in higher critical micellar concentration (CMC), increasing approximately 100 times. The synthesis of the copolymers resulted in molecular weight around 3000 g mol-1 with low polydispersity. The polymer micelles have a hydrodynamic diameter in the range of 100-200 nm and the functionalized sample doesn't show aggregation in the considered pH range. High incorporation efficiency was obtained with a minimum percentage of 85%. The drug release profile and linearization from the Peppas model confirmed the interaction of methotrexate with the hydrophobic segment of the copolymer and its release mechanism by relaxation and/or degradation of the chains, making PEG-b-PCL micelles suitable candidates for hydrophobic drug delivery systems.

Soluble CD14 Subtype-A New Biomarker in Predicting the Outcome of Critically Ill Septic Patients.

BACKGROUND: We evaluated the role of presepsin (soluble CD14 subtype, sCD14-ST) in predicting the outcome of critically ill septic patients in parallel with procalcitonin and C-reactive protein. METHODS: This study was an observational, prospective study that enrolled 58 surgical and medical intensive care unit patients with suspected sepsis. All studied subjects were retrospectively stratified into survivors and nonsurvivors based on 28 days survival and according to microbiological results in blood culture positive and negative groups. Plasma and serum samples from each patient were collected at admission (T-0), after 24-48 hours (T-1) and after 7 days (T-2). Statistics were obtained using Student׳s t test and ANOVA, as well as Bonferroni post hoc test. Receiver-operating characteristic (ROC) analysis was also performed. RESULTS: Presepsin levels were significantly higher at T-0 (P = 0.0007), at T-1 (P < 0.0001) and at T-2 (P < 0.0001) in nonsurvivors versus survivors at the same time point. Presepsin concentrations were significantly increased at T-0 (P = 0.0073), T1 (P = 0.0111) and T2 (P = 0.0167) in patients with positive blood cultures in comparison to patients with negative cultures at the same time. For all time periods evaluated, presepsin data from nonsurviving and surviving individuals were subjected to ROC analysis that demonstrated an excellent accuracy and significant area under the ROC curve (P < 0.0001). Results of multivariate analysis indicated presepsin as a predictive independent variable among prognosis markers at T-0 (P = 0.016). CONCLUSIONS: Presepsin revealed an optimal prognostic performance in patients with severe sepsis and provided interesting diagnostic value. Prediction of outcome in critically ill patients is crucial to optimize management decisions and level of treatment.

Levosimendan for Hemodynamic Support after Cardiac Surgery.

BACKGROUND: Acute left ventricular dysfunction is a major complication of cardiac surgery and is associated with increased mortality. Meta-analyses of small trials suggest that levosimendan may result in a higher rate of survival among patients undergoing cardiac surgery. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving patients in whom perioperative hemodynamic support was indicated after cardiac surgery, according to prespecified criteria. Patients were randomly assigned to receive levosimendan (in a continuous infusion at a dose of 0.025 to 0.2 µg per kilogram of body weight per minute) or placebo, for up to 48 hours or until discharge from the intensive care unit (ICU), in addition to standard care. The primary outcome was 30-day mortality. RESULTS: The trial was stopped for futility after 506 patients were enrolled. A total of 248 patients were assigned to receive levosimendan and 258 to receive placebo. There was no significant difference in 30-day mortality between the levosimendan group and the placebo group (32 patients [12.9%] and 33 patients [12.8%], respectively; absolute risk difference, 0.1 percentage points; 95% confidence interval [CI], -5.7 to 5.9; P=0.97). There were no significant differences between the levosimendan group and the placebo group in the durations of mechanical ventilation (median, 19 hours and 21 hours, respectively; median difference, -2 hours; 95% CI, -5 to 1; P=0.48), ICU stay (median, 72 hours and 84 hours, respectively; median difference, -12 hours; 95% CI, -21 to 2; P=0.09), and hospital stay (median, 14 days and 14 days, respectively; median difference, 0 days; 95% CI, -1 to 2; P=0.39). There was no significant difference between the levosimendan group and the placebo group in rates of hypotension or cardiac arrhythmias. CONCLUSIONS: In patients who required perioperative hemodynamic support after cardiac surgery, low-dose levosimendan in addition to standard care did not result in lower 30-day mortality than placebo. (Funded by the Italian Ministry of Health; CHEETAH ClinicalTrials.gov number, NCT00994825 .).

Skin grafting for the treatment of chronic leg ulcers - a systematic review in evidence-based medicine.

Skin grafting is one of the most common surgical procedures in the area of non-healing wounds by which skin or a skin substitute is placed over a wound to replace and regenerate the damaged skin. Chronic leg ulcers are an important problem and a major source of expense for Western countries and for which many different forms of treatment have been used. Skin grafting is a method of treatment that decreases the area of chronic leg ulcers or heals them completely, thus improving a patient's quality of life. Skin grafting is an old technique, rediscovered during the first and second world wars as the main treatment for wound closure. Nowadays, skin grafting has a pivotal role in the context of modern wound healing and tissue regeneration. The aim of this review was to track and to analyse the specific outcomes this technique achieved, especially in the last decade, in relation to venous, arterial, diabetic, rheumatoid and traumatic leg ulcers. Our main findings indicate that autologous split-thickness skin grafting still remains the gold standard in terms of safety and efficacy for chronic leg ulcers; skin grafting procedures have greater success rates in chronic venous leg ulcers compared to other types of chronic leg ulcers; skin tissue engineering, also supported by genetic manipulation, is quickly expanding and, in the near future, may provide even better outcomes in the area of treatments for long-lasting chronic wounds.

A randomized controlled trial of levosimendan to reduce mortality in high-risk cardiac surgery patients (CHEETAH): Rationale and design.

OBJECTIVE: Patients undergoing cardiac surgery are at risk of perioperative low cardiac output syndrome due to postoperative myocardial dysfunction. Myocardial dysfunction in patients undergoing cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with 3 beneficial cardiovascular effects (inotropic, vasodilatory, and anti-inflammatory), which appears effective in improving clinically relevant outcomes. DESIGN: Double-blind, placebo-controlled, multicenter randomized trial. SETTING: Tertiary care hospitals. INTERVENTIONS: Cardiac surgery patients (n = 1,000) with postoperative myocardial dysfunction (defined as patients with intraaortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 µg/[kg min]) or placebo for 24-48 hours. MEASUREMENTS AND MAIN RESULTS: The primary end point will be 30-day mortality. Secondary end points will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open-label levosimendan, and length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduces 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction. CONCLUSIONS: This trial is planned to determine whether levosimendan could improve survival in patients with postoperative low cardiac output syndrome. The results of this double-blind, placebo-controlled randomized trial may provide important insights into the management of low cardiac output in cardiac surgery.

Albumin administration prevents the onset of pressure ulcers in intensive care unit patients.

Pressure ulcers (PUs) are a common problem in critically ill patients admitted to the intensive care units (ICUs) and they account for more than 70% of patients with low serum albumin at admission. The aim of this study was to test the efficacy of intravenous administration of albumin in patients with low serum albumin < 3·3 g/dl. In a 1-year period, a total of 73 patients were admitted to the ICU (males 45, 61·64% and females 28, 38·36%); of these, 21 patients were admitted with hypoalbuminaemia (serum albumin < 3·3 g/dl) and randomised into two groups: 11 patients were treated with 25 g intravenous albumin for the first 3 days within the first week of ICU stay (group A) and 10 patients did not receive albumin (group B). Three patients (27·27%) showed the onset of PUs in group A, whereas seven patients (70%) showed the onset of PUs within the first 7 days of stay in group B. Moreover, ulcers of group B were more severe than those of group A. This study shows that intravenous administration of albumin reduces the onset of PUs in patients admitted to the ICU and in some cases it also reduces the risk of progression to advanced stages of PUs.

Effect of fenoldopam on use of renal replacement therapy among patients with acute kidney injury after cardiac surgery: a randomized clinical trial.

IMPORTANCE: No effective pharmaceutical agents have yet been identified to treat acute kidney injury after cardiac surgery. OBJECTIVE: To determine whether fenoldopam reduces the need for renal replacement therapy in critically ill cardiac surgery patients with acute kidney injury. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, double-blind, placebo-controlled, parallel-group study from March 2008 to April 2013 in 19 cardiovascular intensive care units in Italy. We randomly assigned 667 patients admitted to intensive care units after cardiac surgery with early acute kidney injury (≥50% increase of serum creatinine level from baseline or oliguria for ≥6 hours) to receive fenoldopam (338 patients) or placebo (329 patients). We used a computer-generated permuted block randomization sequence for treatment allocation. All patients completed their follow-up 30 days after surgery, and data were analyzed according to the intention-to-treat principle. INTERVENTIONS: Continuous infusion of fenoldopam or placebo for up to 4 days with a starting dose of 0.1 µg/kg/min (range, 0.025-0.3 µg/kg/min). MAIN OUTCOMES AND MEASURES: The primary end point was the rate of renal replacement therapy. Secondary end points included mortality (intensive care unit and 30-day mortality) and the rate of hypotension during study drug infusion. RESULTS: The study was stopped for futility as recommended by the safety committee after a planned interim analysis. Sixty-nine of 338 patients (20%) allocated to the fenoldopam group and 60 of 329 patients (18%) allocated to the placebo group received renal replacement therapy (P = .47). Mortality at 30 days was 78 of 338 (23%) in the fenoldopam group and 74 of 329 (22%) in the placebo group (P = .86). Hypotension occurred in 85 (26%) patients in the fenoldopam group and in 49 (15%) patients in the placebo group (P = .001). CONCLUSIONS AND RELEVANCE: Among patients with acute kidney injury after cardiac surgery, fenoldopam infusion, compared with placebo, did not reduce the need for renal replacement therapy or risk of 30-day mortality but was associated with an increased rate of hypotension. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00621790.

Low serum albumin level as an independent risk factor for the onset of pressure ulcers in intensive care unit patients.

Critically ill patients are at high risk of developing pressure ulcers (PUs) and patients who develop PUs remain significantly longer in the intensive care unit (ICU) with significantly increased morbidity and mortality. Therefore, the identification of patients at truly increased risk is important. The aim of this study was to examine the association of low serum albumin present at admission in ICU patients with the onset of PUs. We conducted a retrospective cohort study on 610 patients who were admitted to intensive care unit. Level of serum albumin and other biochemical indices, recorded at the time of admission, were collected. We collected information about PU occurrence after admission and conducted a statistical analysis with biomarkers at ICU admission and during hospital stay. The incidence of PU in the ICUs was 31% and about 70% of patients with PUs had hypoalbuminemia at admission. The lowest values of serum albumin in patients with PUs were directly proportional to the severity of ulcers. In this study, we found a close association between serum albumin and PUs. In fact serum albumin was negatively correlated with PU and may be considered one of the independent determinants of PU occurrence in patients admitted to ICUs.

Coupled plasma filtration adsorption reduces serum bilirubine in a case of acute hypoxic hepatitis secondary to cardiogenic shock.

Hypoxic hepatitis (HH) is a severe complication of postoperative low output syndrome, associated with high mortality rates despite appropriate drug therapy. Recently several extracorporeal supportive techniques have become available. We describe the case of a 70-year-old woman who developed HH secondary to cardiogenic shock after cardiac surgery. CPFA proved to be a valid tool for concomitant hemodynamic support and organ replacement therapy.

Impact of clonidine administration on delirium and related respiratory weaning after surgical correction of acute type-A aortic dissection: results of a pilot study.

Delirium and transient neurologic dysfunctions (TND) often complicate the postoperative course after surgery for acute type-A aortic dissection (AAD). We evaluated the role of clonidine on neurological outcome and respiratory function in 30 consecutive patients undergoing surgery for AAD. Patients were prospectively randomized to receive either clonidine (0.5 microg/kg bolus, followed by continuous infusion at 1-2 microg/kg/h) or placebo (NaCl 0.9%) in on starting and throughout the weaning period from the mechanical ventilation. Incidence of delirium and TND, Delirium Detection Score (DDS), weaning parameters [respiratory rate to tidal volume ratio - f/VT; pressure-frequency product (PFP); partial pressure of arterial oxygen to fractional inspired oxygen concentration (PaO(2)/FiO(2)); partial pressure of carbon dioxide (PaCO(2))], weaning duration and intensive care unit (ICU) length of stay were recorded. The two groups were similar for preoperative and operative variables and also for the incidence of postoperative complications. DDS was lower in the clonidine group (P<0.001). Patients weaned with clonidine showed lower f/VT and PFP, higher PaO(2)/FiO(2) and PaCO(2), lower DDS, weaning period and the related ICU length of stay (P<0.001). This was further confirmed in patients developing delirium/TND. Intravenous clonidine after surgery for AAD reduces the severity of delirium, improves the respiratory function, shortens the weaning duration and the ICU length of stay.

A case of acute quadriplegia complicating Mediterranean spotted fever.

Mediterranean spotted fever is a rickettsiosis caused by Rickettsia conorii. Mediterranean spotted fever is considered to be a benign disease, however, approximately 10% of patients present with a severe systemic manifestation in which neurologic involvement occurs. We present a case of an 80-year-old man with a R. conorii infection who developed an acute quadriplegia secondary to an axonal polyneuropathy. The characteristic tache noire was observed on the lateral region of the thigh and elevated IgM antibody titres against R. conorii were detected by an indirect immunofluorescence test.

Troponin I and lactate from coronary sinus predict cardiac complications after myocardial revascularization.

BACKGROUND: Postoperative troponin I and lactate elevation are related to cardiac complications after myocardial revascularization. We sought to evaluate earlier predictive value for acute myocardial infarction (AMI) and myocardial damage of troponin I and lactate after myocardial revascularization. METHODS: In all, 183 consecutive isolated myocardial revascularizations were prospectively enrolled in the study. Troponin I and lactate were sampled preoperatively and intraoperatively from the coronary sinus, and at 12, 24, 48, and 72 hours. Hospital outcome was recorded. Receiver operating curves for coronary sinus troponin I and lactate were constructed to differentiate patients with or without AMI and myocardial damage. RESULTS: Acute myocardial infarction developed in 6 patients (3.2%), with higher troponin I and lactate at all time points (p < 0.05), longer intubation time (p = 0.003), intensive care unit stay (p = 0.001), hospital stay (p = 0.001), higher atrial fibrillation (p = 0.001), and worse ventricular function (p = 0.001). Myocardial damage developed in 6 patients (3.2%), showing higher troponin I at all time points (p < 0.001), higher intraoperative lactate (p = 0.04), longer intubation time (p = 0.005), and intensive care unit stay (p = 0.03). Receiver operating characteristic curves demonstrated coronary sinus troponin I greater than 0.94 microg/L (area under the curve [AUC] 0.820 +/- 0.075; sensitivity 90.0%, specificity 68.9%) as a better discriminator between patients with or without AMI than lactate level greater than 2.85 mmol/L (AUC 0.686 +/- 0.090; sensitivity 80.0%; specificity 72.9%); troponin I greater than 0.65 microg/L was a better discriminator between patients with or without myocardial damage (AUC 0.834 +/- 0.061; sensitivity 93.8%, specificity 71.5%), than lactate greater than 2.05 mmol/L (AUC 0.627 +/- 0.067; sensitivity 87.5%; specificity 70.7%). CONCLUSIONS: Coronary sinus troponin I and lactate are predictive for cardiac complications after myocardial revascularization. Intraoperative biochemical assays should be routinely performed to establish preventative strategies to reduce further myocardial damage.