Effects of controlled ovarian stimulation on vascular barrier and endothelial glycocalyx: a pilot study.

PURPOSE: Controlled ovarian stimulation significantly amplifies the number of maturing and ovulated follicles as well as ovarian steroid production. The ovarian hyperstimulation syndrome (OHSS) increases capillary permeability and fluid extravasation. Vascular integrity intensely is regulated by an endothelial glycocalyx (EGX) and we have shown that ovulatory cycles are associated with shedding of EGX components. This study investigates if controlled ovarian stimulation impacts on the integrity of the endothelial glycocalyx as this might explain key pathomechanisms of the OHSS. METHODS: Serum levels of endothelial glycocalyx components of infertility patients (n=18) undergoing controlled ovarian stimulation were compared to a control group of healthy women with regular ovulatory cycles (n=17). RESULTS: Patients during luteal phases of controlled ovarian stimulation cycles as compared to normal ovulatory cycles showed significantly increased Syndecan-1 serum concentrations (12.6 ng/ml 6.1125th-19.1375th to 13.9 ng/ml 9.625th-28.975th; p=0.026), indicating shedding and degradation of the EGX. CONCLUSION: A shedding of EGX components during ovarian stimulation has not yet been described. Our study suggests that ovarian stimulation may affect the integrity of the endothelial surface layer and increasing vascular permeability. This could explain key features of the OHSS and provide new ways of prevention of this serious condition of assisted reproduction.

[Cardiorespiratory effects of perioperative positioning techniques]. / Kardiorespiratorische Effekte perioperativer Positionierungsmaßnahmen.

The supine position is still the most frequently used type of positioning during surgical procedures. Positions other than the supine position lead to physiological alterations that have a relevant influence on the course of anesthesia and surgery. As a matter of principle, hemodynamic stability is at risk because venous blood is pooled in the lower positioned body parts. In addition, head down positions (Trendelenburg position) may lead to an impairment of respiratory function by reducing lung volumes as well as lung compliance. Upright positions (beach chair position) are characterized by a relative hypovolemia accompanied by a reduction of mean arterial pressure, cardiac output and stroke volume, whereas pulmonary functions remain unchanged. Some severe adverse events have been described in the literature (e.g. intraoperative apoplexy, postoperative blindness). The pathophysiological principles and effects of hemodynamic alterations as well as potential strategies to avoid complications are presented and discussed in this lead article. Head down positions, especially the Trendelenburg position, cause a relative (intrathoracic) hypervolemia and an increase in cardiac preload that is usually well-tolerated in patients without heart problems; however, the Trendelenburg position, especially if combined with a capnoperitoneum, significantly impairs pulmonary function, can have a negative effect on intracerebral pressure and may reduce blood flow of intra-abdominal organs. The pathophysiological intraoperative changes caused by Trendelenburg positioning are described and approaches suitable for risk reduction are discussed. The prone position and lateral decubitus position have little influence on the intraoperative homeostasis. Nevertheless, there is an ongoing discussion concerning the efficacy of a 15° left lateral position during caesarean section, which is also discussed in a separate section of this review.

Screening for delirium after surgery: validation of the 4 A's test (4AT) in the post-anaesthesia care unit.

Postoperative delirium is common and has multiple adverse consequences. Guidelines recommend routine screening for postoperative delirium beginning in the post-anaesthesia care unit. The 4 A's test (4AT) is a widely used assessment tool for delirium but there are no studies evaluating its use in the post-anaesthesia care unit. We evaluated the performance of the 4AT in the post-anaesthesia care unit in a tertiary German medical centre. Adults who were able to provide informed consent, were not scheduled for postoperative intensive care, and who did not have dementia or severe neuropsychiatric disorders underwent screening by trained research staff with the Nurse Delirium Screening Scale and a new German translation of the 4AT in a random order at the point of discharge from the post-anaesthesia care unit. Reference standard assessment of delirium was psychiatric evaluation by experienced clinicians. Five hundred and forty-three patients (mean age (SD) 52 (18) years) were analysed; 22 (4.1%) patients developed delirium. The sensitivity and specificity of the 4AT were 95.5% (95%CI 77.2-99.9) and 99.2% (95%CI 98.1-99.8), respectively. The area under the receiver operator characteristic curve was 0.998 (95%CI 0.995-1.000). The Nursing Delirium Screening Scale had a sensitivity of 27.3% (95%CI 10.7-50.2) and specificity of 99.4% (95%CI 98.3-99.9), with an area under the curve of 0.761 (95%CI 0.629-0.894). These findings suggest that the 4AT is an effective and robust instrument for delirium detection in the post-anaesthesia care unit.

State of the art in fluid and volume therapy : A user-friendly staged concept. English version.

Adequate intraoperative infusion therapy is essential for the perioperative outcome of a patient. Both hypo- and hypervolemia can lead to an increased rate of perioperative complications and to a worse outcome. Perioperative infusion therapy should therefore be needs-based. The primary objective is the maintenance of preoperative normovolemia using a rational infusion strategy. Perioperative fluid losses should be differentiated from volume losses due to surgical bleeding or protein losses into the interstitial space. Fluid loss via urine excretion or insensible perspiration (0.5-1.0 ml/kg/h) should be replaced with balanced, isooncotic, crystalloid infusion solutions in a ratio of 1:1. Volume therapy stage 1: intraoperative volume losses up to a blood loss corresponding to 20% of the patient's total blood volume are compensated for by balanced crystalloids in a ratio of 4-5:1. Stage 2: blood losses exceeding this level are to be treated with isooncotic colloids (preferably balanced) in a 1:1 ratio. In this regard taking into consideration the contraindications, e. g., sepsis, burns, critical illness (usually patients in the intensive care unit), impaired renal function or renal replacement therapy, intracranial hemorrhage, or severe coagulopathy, artificial colloids such as hydroxyethyl starch (HES) can be used perioperatively for volume replacement. Stage 3: if an allogeneic blood transfusion is indicated, blood and blood products are applied in a differentiated manner.

[Physiological changes during pregnancy]. / Physiologische Veränderungen in der Schwangerschaft.

The physiological state of a woman experiences multiple changes in the body during pregnancy. These alterations could be of particular importance in the medical care of pregnant women. This review article highlights the physiological developments of various organ systems throughout gestation with a focus on endocrinology, the cardiovascular system, hematology, the respiratory system and water balance.

[State of the art in fluid and volume therapy : A user-friendly staged concept]. / Stand der Wissenschaft in der Flüssigkeits- und Volumentherapie : Ein anwenderfreundliches Stufenkonzept.

Adequate fluid therapy is highly important for the perioperative outcome of our patients. Both, hypovolemia and hypervolemia can lead to an increase in perioperative complications and can impair the outcome. Therefore, perioperative infusion therapy should be target-oriented. The main target is to maintain the patient's preoperative normovolemia by using a sophisticated, rational infusion strategy.Perioperative fluid losses should be discriminated from volume losses (surgical blood loss or interstitial volume losses containing protein). Fluid losses as urine or perspiratio insensibilis (0.5-1.0 ml/kg/h) should be replaced by balanced crystalloids in a ratio of 1:1. Volume therapy step 1: Blood loss up to a maximum value of 20% of the patient's blood volume should be replaced by balanced crystalloids in a ratio of 4(-5):1. Volume therapy step 2: Higher blood losses should be treated by using iso-oncotic, preferential balanced colloids in a ratio of 1:1. For this purpose hydroxyethyl starch can also be used perioperatively if there is no respective contraindication, such as sepsis, burn injuries, critically ill patients, renal impairment or renal replacement therapy, and severe coagulopathy. Volume therapy step 3: If there is an indication for red cell concentrates or coagulation factors, a differentiated application of blood and blood products should be performed.

[Knowledge and implementation of the S3 guideline on delirium management in Germany]. / Kenntnis und Umsetzung der S3-Leitlinie zum Delirmanagement in Deutschland.

BACKGROUND: Delirium is a common complication in critical care. The syndrome is often underestimated due to its potentially no less dangerous course as a hypoactive delirium. Therefore, current guidelines ask for a structured, regular and routine screening in all intensive care units. If delirium is diagnosed, symptomatic therapy should be initiated promptly. OBJECTIVES: The aim of the current study was to evaluate recent German anesthetists' strategies regarding delirium care compared to the German guidelines for sedation and delirium in intensive care. METHODS: In an online survey German hospitals' senior anesthetists (n = 922) were interviewed anonymously between May and June 2015 regarding guideline use in delirium management in German intensive care units. In 33 direct questions the anesthetists were invited to answer items regarding the structure of their hospitals, intensive care and delirium therapy in order to review their knowledge of the German delirium guidelines that expired in 2014. RESULTS: The 249 senior anesthetists who responded to the survey, can be associated with (or represent) a quarter of German intensive care beds and cases, respectively. In every tenth clinic that runs an intensive care unit the guideline was unknown. In three of four intensive care units physicians specified a preferred delirium score, the CAM-ICU (49.4 %) is used most frequently. With knowledge of the guidelines more often a recommended delirium score is used (p = 0.017). However, only 53.6 % of the respondents ascertain a score every eight hours and 36 % have no facility for standardized documentation in the records. At intensive care rounds, a possible diagnosis of delirium is an inherent part in only 34.9 % of the responders even with guideline knowledge. The particular gold standard for the therapy of delirium (alphaagonists for vegetative symptoms; 89.6 %, benzodiazepines for anxiety, 77.5 %; antipsychotics in 86.7 % for psychotic symptoms) is implemented more often with growing knowledge of the guidelines. The latter applies to the implementation of structured programs for delirium prophylaxis, cognition and therapy. CONCLUSION: For the first time, this study documents knowledge and implementation of the German S3 guidelines for delirium in intensive care. Overall, the guidelines for delirium care are less well executed than those for sedation. With growing knowledge of the guidelines, diagnosis and treatment of delirium fits the guidelines more frequently. The facility to document a delirium score in intensive records is insufficient. Especially a nursing-based delirium strategy could possibly improve implementation of the guidelines, claiming an eight-hour screening and documentation. However, the small number of hospitals that have integrated the guidelines into in-house standard operating procedures (40 %) shows urgent need for optimization. A re-evaluation involving all relevant caretakers could probably improve the implementation of guidelines in intensive care and perioperative medicine.

[Acute perioperative hemodilution without using hydroxyethyl starch : hemodynamic alterations under "controlled" hypovolemia]. / Akute perioperative Hämodilution ohne Verwendung von Hydroxyethylstärke : Hämodynamische Veränderungen unter "kontrollierter" Hypovolämie.

BACKGROUND: Up to now hydroxyethyl starch preparations have frequently been used to compensate for volume deficits accompanying blood withdrawal during acute normovolemic hemodilution. This approach was questioned with respect to the current limitations for use of hydroxyethyl starch solutions imposed by the European Medicines Agency. Because crystalloids distribute evenly across the whole extracellular compartment, 80 % of the infused solution will be "lost" to the interstitial space. Thus, a physiological adjustment of blood loss caused by hemodilution with crystalloids alone (1:5 ratio) seems hardly feasible and according to current data perhaps not even desirable. A 3:1 ratio (crystalloids versus blood loss) as applied in the current study can be regarded as a practical compromise between physiological needs and recommendations according to the literature (1.4:1) but will lead to moderate hypovolemia the hemodynamic consequences of which are not well described. AIM: The current study investigates the hemodynamic impact of a hemodilution with crystalloids under the precondition of a 3:1 substitution ratio compared to withdrawn blood. METHODS: In the context of acute perioperative hemodilution 10 otherwise healthy women graded I and II on the American Society of Anesthesiologists (ASA) classification scheduled for open gynecological cancer surgery underwent an average blood withdrawal of 1097 ± 285 ml which was substituted by an average of 3430 ± 806 ml of Ringer's lactate. The resulting deficit in blood volume was exactly quantified by a double tracer technique. Hemodynamic changes were evaluated by a combination of thermodilution and pulse contour analysis (PiCCO system®). Subsequently, the remaining volume deficit was compensated by 245 ± 64 ml of a 20 % albumin solution and hemodynamic parameters were again evaluated. RESULTS: When infusing Ringer's lactate in a 3:1 ratio compared to the actual blood loss, the blood volume decreased by 12 %. The volume effect of Ringer's lactate proved to be 17 %. While mean arterial pressure and heart rate remained constant, key hemodynamic parameters changed relevantly during the time course. A significant rise in cardiac output and myocardial contractility could be observed which was accompanied by a decrease in systemic vascular resistance. In contrast, cardiac preload and the parameters representing pulmonary vascular permeability remained unaltered. The infusion of 245 ± 64 ml of a 20 % albumin solution nearly completely restituted blood volume and led to an insignificant rise in systemic vascular resistance but did not normalize cardiac output or myocardial contractility. CONCLUSION: In the study population, the loss of intravascular fluid during perioperative haemodilution could be compensated by an increase in cardiac performance. However, whether patients with a reduced cardiac capacity (i.e. older patients) are capable to improve their cardiac output sufficiently in order to compensate hypovolemia accompanying perioperative haemodilution with crystalloids remains questionable.

Optimization and critical evaluation of decellularization strategies to develop renal extracellular matrix scaffolds as biological templates for organ engineering and transplantation.

The ability to generate patient-specific cells through induced pluripotent stem cell (iPSC) technology has encouraged development of three-dimensional extracellular matrix (ECM) scaffolds as bioactive substrates for cell differentiation with the long-range goal of bioengineering organs for transplantation. Perfusion decellularization uses the vasculature to remove resident cells, leaving an intact ECM template wherein new cells grow; however, a rigorous evaluative framework assessing ECM structural and biochemical quality is lacking. To address this, we developed histologic scoring systems to quantify fundamental characteristics of decellularized rodent kidneys: ECM structure (tubules, vessels, glomeruli) and cell removal. We also assessed growth factor retention--indicating matrix biofunctionality. These scoring systems evaluated three strategies developed to decellularize kidneys (1% Triton X-100, 1% Triton X-100/0.1% sodium dodecyl sulfate (SDS) and 0.02% Trypsin-0.05% EGTA/1% Triton X-100). Triton and Triton/SDS preserved renal microarchitecture and retained matrix-bound basic fibroblast growth factor and vascular endothelial growth factor. Trypsin caused structural deterioration and growth factor loss. Triton/SDS-decellularized scaffolds maintained 3 h of leak-free blood flow in a rodent transplantation model and supported repopulation with human iPSC-derived endothelial cells and tubular epithelial cells ex vivo. Taken together, we identify an optimal Triton/SDS-based decellularization strategy that produces a biomatrix that may ultimately serve as a rodent model for kidney bioengineering.

Neutron study of the magnetism in NiCl2·4SC(NH2)2.

We study the strongly anisotropic quasi-one-dimensional S = 1 quantum magnet NiCl2·4SC(NH2)2 using elastic and inelastic neutron scattering. We demonstrate that a magnetic field splits the excited doublet state and drives the lower doublet state to zero energy at a critical field Hc1. For Hc1 < H < Hc2, where Hc2 indicates the transition to a fully magnetized state, three-dimensional magnetic order is established with the AF moment perpendicular to the magnetic field. We mapped the temperature/magnetic field phase diagram, and we find that the total ordered magnetic moment reaches m(tot) = 2.1 µB at the field µ(0)H = 6 T and is thus close to the saturation value of the fully ordered moment. We study the magnetic spin dynamics in the fully magnetized state for H > Hc2, and we demonstrate the presence of an AF interaction between Ni(2+) on the two interpenetrating sublattices. In the antiferromagnetically ordered phase, the spin-waves that develop from the lower-energy doublet are split into two modes. This is most likely the result of the presence of the AF interaction between the interpenetrating lattices.

Spin ladders and quantum simulators for Tomonaga-Luttinger liquids.

Magnetic insulators have proven to be usable as quantum simulators for itinerant interacting quantum systems. In particular the compound (C(5)H(12)N)(2)CuBr(4) (for short: (Hpip)(2)CuBr(4)) was shown to be a remarkable realization of a Tomonaga-Luttinger liquid (TLL) and allowed us to quantitatively test the TLL theory. Substitution weakly disorders this class of compounds and thus allows us to use them to tackle questions pertaining to the effect of disorder in TLL as well, such as that of the formation of the Bose glass. In this paper we present, as a first step in this direction, a study of the properties of the related (Hpip)(2)CuCl(4) compound. We determine the exchange couplings and compute the temperature and magnetic field dependence of the specific heat, using a finite temperature density matrix renormalization group procedure. Comparison with the measured specific heat at zero magnetic field confirms the exchange parameters and Hamiltonian for the (Hpip)(2)CuCl(4) compound, giving the basis needed to begin studying the disorder effects.

Magnetic frustration in a quantum spin chain: the case of linarite PbCuSO4(OH)2.

We present a combined neutron diffraction and bulk thermodynamic study of the natural mineral linarite PbCuSO4(OH)2, this way establishing the nature of the ground-state magnetic order. An incommensurate magnetic ordering with a propagation vector k=(0,0.186,1/2) was found below T(N)=2.8 K in a zero magnetic field. The analysis of the neutron diffraction data yields an elliptical helical structure, where one component (0.638µ(B)) is in the monoclinic ac plane forming an angle with the a axis of 27(2)°, while the other component (0.833µ(B)) points along the b axis. From a detailed thermodynamic study of bulk linarite in magnetic fields up to 12 T, applied along the chain direction, a very rich magnetic phase diagram is established, with multiple field-induced phases, and possibly short-range-order effects occurring in high fields. Our data establish linarite as a model compound of the frustrated one-dimensional spin chain, with ferromagnetic nearest-neighbor and antiferromagnetic next-nearest-neighbor interactions. Long-range magnetic order is brought about by interchain coupling 1 order of magnitude smaller than the intrachain coupling.

Simultaneous polarized neutron reflectometry and anisotropic magnetoresistance measurements.

A novel experimental facility to carry out simultaneous polarized neutron reflectometry (PNR) and anisotropic magnetoresistance (AMR) measurements is presented. Performing both techniques at the same time increases their strength considerably. The proof of concept of this method is demonstrated on a CoO/Co bilayer exchange bias system. Although information on the same phenomena, such as the coercivity or the reversal mechanism, can be separately obtained from either of these techniques, the simultaneous application optimizes the consistency between both. In this way, possible differences in experimental conditions, such as applied magnetic field amplitude and orientation, sample temperature, magnetic history, etc., can be ruled out. Consequently, only differences in the fundamental sensitivities of the techniques can cause discrepancies in the interpretation between the two. The almost instantaneous information obtained from AMR can be used to reveal time-dependent effects during the PNR acquisition. Moreover, the information inferred from the AMR measurements can be used for optimizing the experimental conditions for the PNR measurements in a more efficient way than with the PNR measurements alone.

Effect of decomposition of the Cr-Fe-Co rich phase of AlCoCrCuFeNi high entropy alloy on magnetic properties.

Splat-quenched, as-cast and aged (2h at 600 °C after casting) AlCoCrCuFeNi high entropy alloys were investigated by means of transmission electron microscopy and three-dimensional atom probe (3D-AP). 3D-AP revealed anti-correlated fluctuations of the Cr and Fe-Co compositions in Cr-Fe-Co-rich regions of the as-cast alloy. The ferromagnetic behavior of AlCoCrCuFeNi high entropy alloy was correlated with the decomposition of the Cr-Fe-Co-rich regions into ferromagnetic Fe-Co-rich and antiferromagnetic Cr-rich domains, the size of which was determined by statistical analysis of 3D-AP data. The splat-quenched alloy showed a softer magnetic behavior as compared to the as-cast and aged alloys. The aged alloy possessed a higher saturation magnetization and coercivity as compared to the as-cast alloy.

Magnetism and superconductivity driven by identical 4f states in a heavy-fermion metal.

The apparently inimical relationship between magnetism and superconductivity has come under increasing scrutiny in a wide range of material classes, where the free energy landscape conspires to bring them in close proximity to each other. Particularly enigmatic is the case when these phases microscopically interpenetrate, though the manner in which this can be accomplished remains to be fully comprehended. Here, we present combined measurements of elastic neutron scattering, magnetotransport, and heat capacity on a prototypical heavy fermion system, in which antiferromagnetism and superconductivity are observed. Monitoring the response of these states to the presence of the other, as well as to external thermal and magnetic perturbations, points to the possibility that they emerge from different parts of the Fermi surface. Therefore, a single 4f state could be both localized and itinerant, thus accounting for the coexistence of magnetism and superconductivity.

Quantum criticality in an Ising chain: experimental evidence for emergent E8 symmetry.

Quantum phase transitions take place between distinct phases of matter at zero temperature. Near the transition point, exotic quantum symmetries can emerge that govern the excitation spectrum of the system. A symmetry described by the E8 Lie group with a spectrum of eight particles was long predicted to appear near the critical point of an Ising chain. We realize this system experimentally by using strong transverse magnetic fields to tune the quasi-one-dimensional Ising ferromagnet CoNb2O6 (cobalt niobate) through its critical point. Spin excitations are observed to change character from pairs of kinks in the ordered phase to spin-flips in the paramagnetic phase. Just below the critical field, the spin dynamics shows a fine structure with two sharp modes at low energies, in a ratio that approaches the golden mean predicted for the first two meson particles of the E8 spectrum. Our results demonstrate the power of symmetry to describe complex quantum behaviors.

[Hypernatremic alkalosis. Possible counterpart of hyperchloremic acidosis in intensive care patients?]. / Hypernatriämische Alkalose. Pendant zur hyperchlorämischen Acidose in der Intensivmedizin?

BACKGROUND: With broad acceptance of Stewart's acid-base model "hyperchloremic acidosis" is regarded as an independent form of metabolic disorder. It is unknown whether hypernatremia plays a corresponding role with respect to the development of alkalosis. METHODS: A total of 201 artificially ventilated, critically ill patients were monitored for hypernatremic episodes. Inclusion criterion was a serum sodium concentration above 145 mmol/l. RESULTS: In 20 patients a total of 78 periods of elevated plasma sodium levels lasting at least 24 h were observed. In 86% of these cases sodium and chloride concentrations were simultaneously increased. The development of alkalosis correlated with the strong ion difference (r=0.80, p<0.01) but not with the serum sodium concentration (r=-0.031, p=0.78). In cases without accompanying hyperchloremia (13%) metabolic alkalosis regularly occurred and a correlation between serum sodium concentration and base excess could be verified (r=0.66, p=0.03). Alkalosis occurred in 84.8% of cases where the strong on difference exceeded 39 mmol/l. CONCLUSION: From the available data hypernatremic alkalosis could not be defined as an independent metabolic disorder. In would seem more appropriate to use the term "strong ion alkalosis" in this context.

Dirac strings and magnetic monopoles in the spin ice Dy2Ti2O7.

Sources of magnetic fields-magnetic monopoles-have so far proven elusive as elementary particles. Condensed-matter physicists have recently proposed several scenarios of emergent quasiparticles resembling monopoles. A particularly simple proposition pertains to spin ice on the highly frustrated pyrochlore lattice. The spin-ice state is argued to be well described by networks of aligned dipoles resembling solenoidal tubes-classical, and observable, versions of a Dirac string. Where these tubes end, the resulting defects look like magnetic monopoles. We demonstrated, by diffuse neutron scattering, the presence of such strings in the spin ice dysprosium titanate (Dy2Ti2O7). This is achieved by applying a symmetry-breaking magnetic field with which we can manipulate the density and orientation of the strings. In turn, heat capacity is described by a gas of magnetic monopoles interacting via a magnetic Coulomb interaction.