How Detergents Dissolve Polymeric Micelles: Kinetic Pathways of Hybrid Micelle Formation in SDS and Block Copolymer Mixtures.

Mixtures of amphiphilic polymers and surfactants are used in a wide range of applications, e.g., pharmaceuticals, detergents, cosmetics, and drug delivery systems. Still, many questions remain on how the structure and, in particular, the kinetics of block copolymer micelles are affected in the presence of surfactants and what controls the solubilization kinetics. In this work, we have studied the stability and solubilization kinetics of block copolymer micelles upon the addition of the surfactant sodium dodecyl sulfate (SDS) using small-angle X-ray/neutron scattering. The ability of the surfactant to dissolve polymer micelles or form mixed micelles has been investigated using two types of amphiphilic polymers, poly(ethylene-alt-propylene)-poly(ethylene oxide) (PEP1-PEO20) and n-alkyl-functionalized PEO (C28-PEO5). The exchange kinetics of C28-PEO5 micelles are in the order of hours, while PEP1-PEO20 micelles are known to be frozen on a practical timescale. In this work, we show that the addition of SDS to PEP1-PEO20 provides virtually no solubilization, even after an extended period of time. However, upon adding SDS to C28-PEO5 micelles, we observe micellar dissolution and formation of mixed micelles occurring on the timescale of hours. Using a coexistence model of mixed and neat micelles, the SAXS data were analyzed to provide detailed structural parameters over time. First, we observe a fast fragmentation/fission step followed by a slow reorganization process. The latter process is essentially independent of concentration at low volume fraction but is greatly accelerated at larger concentrations. This might indicate a crossover from a predominance of molecular exchange to fusion/fission processes.

[Changes in the patient population with proximal femur fractures over the last decade : Incidence, age, comorbidities, and length of stay]. / Veränderung der Patientenklientel mit hüftgelenknahen Femurfrakturen in der letzten Dekade : Inzidenz, Alter, Nebenerkrankungen und Liegezeiten.

BACKGROUND: Over the last decade, the percentage of people >65 years has increased from 16.6% to 20.7%. In industrialized countries, the annual incidence in people >65 years with a proximal femur fracture is about 600-900 per 100,000 population. The incidence will increase by 3-5% per year. Guidelines advocate early surgery as soon as possible but within 24 h. External quality control requires surgical treatment within 48 h. In this study, the changes in the patient population with proximal femur fractures and their treatment during the last decade were investigated. METHODS: From 2005-2014, data of all patients ≥65 years with proximal femur fractures were recorded. The patients were treated in a level 1 trauma center certified by the German Society for Trauma Surgery. The evaluation was carried out by means of descriptive statistics. RESULTS: In all, 2093 patients with proximal femur fractures (1164 trochanteric neck fractures and 929 femoral neck fractures) were evaluated. The annual increase in the percentage of patients was 1.5-2%. Over the decade, the percentage of patients increased by 20% and the average age increased by 2 years. There were no changes in comorbidities or case mix index during the investigation period. Despite the increase of the preoperative waiting times, a decrease in the total length of stay was found. DISCUSSION: The increase in the number of patients, as well as the requirements of the guidelines and external quality control are relevant challenges for the hospitals. More human and material resources (e. g., surgical capacity) are needed. The increase in the age of the patients, their comorbidities, and medication must be taken into account, e. g., in the context of geriatric orthopedic trauma centers.

Studying Soft-matter and Biological Systems over a Wide Length-scale from Nanometer and Micrometer Sizes at the Small-angle Neutron Diffractometer KWS-2.

The KWS-2 SANS diffractometer is dedicated to the investigation of soft matter and biophysical systems covering a wide length scale, from nm to µm. The instrument is optimized for the exploration of the wide momentum transfer Q range between 1x10-4 and 0.5 Å-1 by combining classical pinhole, focusing (with lenses), and time-of-flight (with chopper) methods, while simultaneously providing high-neutron intensities with an adjustable resolution. Because of its ability to adjust the intensity and the resolution within wide limits during the experiment, combined with the possibility to equip specific sample environments and ancillary devices, the KWS-2 shows a high versatility in addressing the broad range of structural and morphological studies in the field. Equilibrium structures can be studied in static measurements, while dynamic and kinetic processes can be investigated over time scales between minutes to tens of milliseconds with time-resolved approaches. Typical systems that are investigated with the KWS-2 cover the range from complex, hierarchical systems that exhibit multiple structural levels (e.g., gels, networks, or macro-aggregates) to small and poorly-scattering systems (e.g., single polymers or proteins in solution). The recent upgrade of the detection system, which enables the detection of count rates in the MHz range, opens new opportunities to study even very small biological morphologies in buffer solution with weak scattering signals close to the buffer scattering level at high Q. In this paper, we provide a protocol to investigate samples with characteristic size levels spanning a wide length scale and exhibiting ordering in the mesoscale structure using KWS-2. We present in detail how to use the multiple working modes that are offered by the instrument and the level of performance that is achieved.

Tuning the instrument resolution using chopper and time of flight at the small-angle neutron scattering diffractometer KWS-2.

Following demand from the user community regarding the possibility of improving the experimental resolution, the dedicated high-intensity/extended Q-range SANS diffractometer KWS-2 of the Jülich Centre for Neutron Science at the Heinz Maier-Leibnitz Center in Garching was equipped with a double-disc chopper with a variable opening slit window and time-of-flight (TOF) data acquisition option. The chopper used in concert with a dedicated high-intensity velocity selector enables the tuning at will of the wavelength resolution Δλ/λ within a broad range, from 20% (standard) down to 2%, in a convenient and safe manner following pre-planned or spontaneous decisions during the experiment. The new working mode is described in detail, and its efficiency is demonstrated on several standard samples with known properties and on a completely new crystallizable copolymer system, which were investigated using both the conventional (static) and TOF modes.

Studying the concentration dependence of the aggregation number of a micellar model system by SANS.

We present a small-angle neutron scattering (SANS) structural characterization of n-alkyl-PEO polymer micelles in aqueous solution with special focus on the dependence of the micellar aggregation number on increasing concentration. The single micellar properties in the dilute region up to the overlap concentration ϕ* are determined by exploiting the well characterized unimer exchange kinetics of the model system in a freezing and diluting experiment. The micellar solutions are brought to thermodynamic equilibrium at high temperatures, where unimer exchange is fast, and are then cooled to low temperatures and diluted to concentrations in the limit of infinite dilution. At low temperatures the kinetics, and therefore the key mechanism for micellar rearrangement, is frozen on the experimental time scale, thus preserving the micellar structure in the dilution process. Information about the single micellar structure in the semidilute and concentrated region are extracted from structure factor analysis at high concentrations where the micelles order into fcc and bcc close packed lattices and the aggregation number can be calculated by geometrical arguments. This approach enables us to investigate the aggregation behavior in a wide concentration regime from dilute to 6·Ï•*, showing a constant aggregation number with concentration over a large concentration regime up to a critical concentration about three times ϕ*. When exceeding this critical concentration, the aggregation number was found to increase with increasing concentration. This behavior is compared to scaling theories for star-like polymer micelles.

A unique access for the ablation catheter to treat electrical storm in a patient with extracorporeal life support.

AIMS: Extracorporeal membrane oxygenation (ECMO) is a very effective bridging therapy in patients with cardiogenic shock. To perform coronary angiography in these patients our group developed an unique system to get urgent vascular access with minimal additional vascular complication risk. The 6 Fr coronary catheters are introduced through a standard Y-connector, which is inserted into the arterial cannula of the ECMO-line close to the patient, the blind end of which is then equipped with a haemostatic valve (Check-Flo Performer accessory adapter, Cook Medical, USA). To the best of our knowledge, we here present the first patient, in whom this system had been used to insert an 8 Fr radiofrequency ablation catheter to treat incessant ventricular fibrillation. METHODS AND RESULTS: A 66-year-old patient had been transferred with electrical storm 5 days after an acute MI. After failed interventional and medical therapies an ECMO system had been inserted (right femoral artery cannula 15 Fr, left femoral vein cannula 21 Fr) and an electrophysiological study had been performed because of incessant ventricular fibrillation episodes, which always were induced by the same ventricular premature beat (VPB). During this first EP study over the left femoral artery the VPB could be targeted and successfully ablated. Unfortunately the VPB recovered again after some days so a second EP study had to be performed. This time the left femoral artery could not be used because of a postinterventional complication so we used the arterial cannula of the ECMO system as the access for the ablation catheter using a Y-connector. Using this way again a successful ablation procedure could be performed, after getting familiar with manipulation the ablation catheter over the ECMO cannula and with the help of different curved ablation catheters. The issue of compromising of the effective lumen of the arterial cannula by the ablation catheter`s cross sectional area could be overcome with increasing the rotational speed of the V-A ECMO. CONCLUSION: Ablation of ventricular arrhythmias using a Y-connector to insert the ablation catheter into the arterial cannula is feasible in patients with a V-A ECMO system avoiding additional arterial puncture with potentially major vascular complications in critically ill patients. Manipulation of the catheter is not as easy as using a standard sheath but can well be performed after a short habituation.

First experience with the deltastream(R) DP3 in venovenous extracorporeal membrane oxygenation and air-supported inter-hospital transport.

OBJECTIVES: Based on continuous technical innovations and recent research, extracorporeal membrane oxygenation (ECMO) has become a promising tool in the treatment of patients with acute (cardio)pulmonary failure. Nevertheless, any extracorporeal technique requires a high degree of experience and knowledge, so that a restriction to specialized centres seems to be reasonable. As a consequence of this demand, the need for inter-hospital transfer of patients with severely impaired (cardio)pulmonary function is rising. Unfortunately, most of the ECMO devices used in the clinical setting are not suitable for inter-hospital transport because of their size, weight or complexity. In this article, we describe our first experiences with the airborne transport of 6 patients on a new portable, miniaturized and lightweight extracorporeal circulation system, the Medos deltastream® DP3. METHODS: Six patients suffering acute respiratory failure were taken on venovenous ECMO (DP3) out-of-centre and transferred to the University Medical Center Regensburg by helicopter. All cardiorespiratory-relevant parameters of the patients and the technical functioning of the device were continuously monitored and documented. RESULTS: Implantation of the device and air-supported transport were performed without any technical complications. The patients were transported from a distance of 66-178 km, requiring a time of 40-120 min. With the help of the new deltastream® DP3 ECMO device, a prompt stabilization of the cardiopulmonary function could be achieved in all patients. One patient was under ongoing cardiopulmonary resuscitation by the time our ECMO team arrived at the peripheral hospital and died shortly after arrival in the central emergency ward. CONCLUSIONS: Our experience shows that the deltastream® DP3 is an absolutely reliable and safe ECMO device that could gain growing importance in the field of airborne transportation of patients on ECMO due to its unsophisticated, miniaturized and lightweight characteristics.

Quality of life following surgery of ascending aorta and aortic arch with selective antegrade cerebral perfusion.

OBJECTIVE: Surgery of the ascending aorta and aortic arch has been challenging since its inception as neurological complications may occur significantly affecting the quality of life (QOL). METHODS: From January 1998 to December 2007, 79 patients mainly suffering aortic dissection (65%) or true aortic aneurysm (34%) underwent surgery on the aortic arch employing deep hypothermic circulatory arrest and selective antegrade cerebral perfusion. QOL was assessed with the sickness-impact-profile (SIP) comprising 136 questions and 12 categories. RESULTS: All patients underwent replacement of the ascending aorta, combined with a partial (hemiarch) (n = 33; 42%) or total (n = 46, 58%) arch replacement. Thirty-day mortality was 17.7% (n = 14 patients). Perioperatively, three patients (3.8%) suffered a transitory ischemic attack (TIA) and 5.1% patients suffered a stroke. The median score of the complete questionnaire was 4.7, which demonstrates excellent QOL following such complex surgical procedures. The median physical dimension was 2.5 (0; 8), the psychosocial median score was 3.7 (1.2; 16.1), both underline an only minimal impairment of the daily life. CONCLUSION: The QOL after following the surgery of ascending aorta and aortic arch with selective antegrade cerebral perfusion is excellent on the long-term as assessed by the SIP.

First experience with the ultra compact mobile extracorporeal membrane oxygenation system Cardiohelp in interhospital transport.

In patients with severe cardiopulmonary failure extracorporeal assist devices are to support patients during resuscitation, for transportation, until organ recovery, and as bridge to further therapeutic modalities. We report on our first experience with the new Cardiohelp system for interhospital transfer of cardiopulmonarily compromised patients. The Cardiohelp system was used for transportation and in-house treatment in six male patients with a mean age of 41±17 years. Five patients suffered respiratory failure; one patient with acute myocardial infarction was in profound cardiogenic shock. Accordingly, the Cardiohelp system was implanted as a venovenous extracorporeal membrane oxygenation (ECMO) in five patients and as a venoarterial system in one patient. The preECMO ventilation time was 0.5-4 days. The patients were transported to our institution by car (n=1) or helicopter (n=5) over a distance of 80-5850 km. The subsequent in-house ECMO support was continued with the Cardiohelp and lasted for 5-13 days. PostECMO ventilation was one to 25 days. A 100% survival was achieved. The portable Cardiohelp system allows location-independent stabilization of cardiopulmonary compromised patients with consecutive interhospital transfer and in-house treatment. The integrated sensors, which register arterial and venous line pressure, blood temperature, hemoglobin as well as SvO(2), greatly alleviate its management and considerably increase safety.

Emergency use of extracorporeal membrane oxygenation in cardiopulmonary failure.

Severe pulmonary and cardiopulmonary failure resistant to critical care treatment leads to hypoxemia and hypoxia-dependent organ failure. New treatment options for cardiopulmonary failure are necessary even for patients in outlying medical facilities. If these patients are in need of specialized center treatment, additional emergency medical service has to be carried out quick and safely. We describe our experiences with a pumpless extracorporeal lung assist (PECLA/iLA) for out-of-center emergency treatment of hypercapnic respiratory failure and the use of a newly developed hand-held extracorporeal membrane oxygenation (ECMO) system in cardiac, pulmonary, and cardiopulmonary failure (EMERGENCY-LIFE Support System, ELS System, MAQUET Cardiopulmonary AG, Hechingen, Germany). Between March 2000 and April 2009, we used the PECLA System (n = 20) and the ELS System (n = 33) in adult patients. Cannulation was employed using percutaneous vessel access. The new hand-held ELS System consists of a centrifugal pump and a membrane oxygenator, both mounted on a special holder system for storing on a standard patient gurney for air or ground ambulance transfer. Bedside cannulation processes were uneventful. The PECLA System resulted in sufficient CO(2) removal. In all ECMO patients, oxygen delivery and systemic blood flow could be restored and vasopressor support was markedly down. Hospital survival rate in the PECLA group was 50%, and 61% in the ECMO group. Out-of-center emergency treatment of hypercapnic pulmonary failure with pumpless extracorporeal gas exchange and treatment of cardiac, pulmonary, and cardiopulmonary failure with this new hand-held ECMO device is safe and highlyeffective. Patient outcome in cardiopulmonary organ failure could be improved.

Evaluation of a new arterial pressure-based cardiac output device requiring no external calibration.

BACKGROUND: Several techniques have been discussed as alternatives to the intermittent bolus thermodilution cardiac output (COPAC) measurement by the pulmonary artery catheter (PAC). However, these techniques usually require a central venous line, an additional catheter, or a special calibration procedure. A new arterial pressure-based cardiac output (COAP) device (FloTractrade mark, Vigileotrade mark; Edwards Lifesciences, Irvine, CA, USA) only requires access to the radial or femoral artery using a standard arterial catheter and does not need an external calibration. We validated this technique in critically ill patients in the intensive care unit (ICU) using COPAC as the method of reference. METHODS: We studied 20 critically ill patients, aged 16 to 74 years (mean, 55.5 +/- 18.8 years), who required both arterial and pulmonary artery pressure monitoring. COPAC measurements were performed at least every 4 hours and calculated as the average of 3 measurements, while COAP values were taken immediately at the end of bolus determinations. Accuracy of measurements was assessed by calculating the bias and limits of agreement using the method described by Bland and Altman. RESULTS: A total of 164 coupled measurements were obtained. Absolute values of COPAC ranged from 2.80 to 10.80 l/min (mean 5.93 +/- 1.55 l/min). The bias and limits of agreement between COPAC and COAP for unequal numbers of replicates was 0.02 +/- 2.92 l/min. The percentage error between COPAC and COAP was 49.3%. The bias between percentage changes in COPAC (DeltaCOPAC) and percentage changes in COAP (DeltaCOAP) for consecutive measurements was -0.70% +/- 32.28%. COPAC and COAP showed a Pearson correlation coefficient of 0.58 (p < 0.01), while the correlation coefficient between DeltaCOPAC and DeltaCOAP was 0.46 (p < 0.01). CONCLUSION: Although the COAP algorithm shows a minimal bias with COPAC over a wide range of values in an inhomogeneous group of critically ill patients, the scattering of the data remains relative wide. Therefore, the used algorithm (V 1.03) failed to demonstrate an acceptable accuracy in comparison to the clinical standard of cardiac output determination.