Radiographic Cortical Thickness Index Predicts Fragility Fracture in Gaucher Disease.

Background Patients with Gaucher disease (GD) have a high risk of fragility fractures. Routine evaluation of bone involvement in these patients includes radiography and repeated dual-energy x-ray absorptiometry (DXA). However, osteonecrosis and bone fracture may affect the accuracy of DXA. Purpose To assess the utility of DXA and radiographic femoral cortical thickness measurements as predictors of fragility fracture in patients with GD with long-term follow-up (up to 30 years). Materials and Methods Patients with GD age 16 years and older with a detailed medical history, at least one bone image (DXA and/or radiographs), and minimum 2 years follow-up were retrospectively identified using three merged UK-based registries (Gaucherite study, enrollment 2015-2017; Clinical Bone Registry, enrollment 2003-2006; and Mortality Registry, enrollment 1993-2019). Cortical thickness index (CTI) and canal-to-calcar ratio (CCR) were measured by two independent observers, and inter- and intraobserver reliability was calculated. The fracture-predictive value of DXA, CTI, CCR, and cutoff values were calculated using receiver operating characteristic curves. Statistical differences were assessed using univariable and multivariable analysis. Results Bone imaging in 247 patients (123 men, 124 women; baseline median age, 39 years; IQR, 27-50 years) was reviewed. The median follow-up period was 11 years (IQR, 7-19 years; range, 2-30 years). Thirty-five patients had fractures before or at first bone imaging, 23 patients had fractures after first bone imaging, and 189 patients remained fracture-free. Inter- and intraobserver reproducibility for CTI/CCR measurements was substantial (range, 0.96-0.98). In the 212 patients with no baseline fracture, CTI (cutoff, ≤0.50) predicted future fractures with higher sensitivity and specificity (area under the receiver operating characteristic curve [AUC], 0.96; 95% CI: 0.84, 0.99; sensitivity, 92%; specificity, 96%) than DXA T-score at total hip (AUC, 0.78; 95% CI: 0.51, 0.91; sensitivity, 64%; specificity, 93%), femoral neck (AUC, 0.73; 95% CI: 0.50, 0.86; sensitivity, 64%; specificity, 73%), lumbar spine (AUC, 0.69; 95% CI: 0.49, 0.82; sensitivity, 57%; specificity, 63%), and forearm (AUC, 0.78; 95% CI: 0.59, 0.89; sensitivity, 70%; specificity, 70%). Conclusion Radiographic cortical thickness index of 0.50 or less was a reliable independent predictor of fracture risk in Gaucher disease. Clinical trial registration no. NCT03240653 © RSNA, 2022 Supplemental material is available for this article.

Polarization sensitivity and decentralized visual processing in an animal with a distributed visual system.

The marine mollusc Acanthopleura granulata (Mollusca; Polyplacophora) has a distributed visual array composed of hundreds of small image-forming eyes embedded within its eight dorsal shell plates. As in other animals with distributed visual systems, we still have a poor understanding of the visual capabilities of A. granulata and we have yet to learn where and how it processes visual information. Using behavioral trials involving isoluminant looming visual stimuli, we found that A. granulata demonstrates spatial vision with an angular resolution of 6 deg. We also found that A. granulata responds to looming stimuli defined by contrasting angles of linear polarization. To learn where and how A. granulata processes visual information, we traced optic nerves using fluorescent lipophilic dyes. We found that the optic nerves innervate the underlying lateral neuropil, a neural tissue layer that circumnavigates the body. Adjacent optic nerves innervate the lateral neuropil with highly overlapping arborizations, suggesting it is the site of an integrated visuotopic map. Using immunohistochemistry, we found that the lateral neuropil of A. granulata is subdivided into two separate layers. In comparison, we found that a chiton with eyespots (Chiton tuberculatus) and two eyeless chitons (Ischnochiton papillosus and Chaetopleura apiculata) have lateral neuropil that is a singular circular layer without subdivision, findings consistent with previous work on chiton neuroanatomy. Overall, our results suggest that A. granulata effectuates its visually mediated behaviors using a unique processing scheme: it extracts spatial and polarization information using a distributed visual system, and then integrates and processes that information using decentralized neural circuits.

Two sides of the same wing: ventral scales enhance dorsal wing color in the butterfly Speyeria mormonia.

Biological visual signals are often produced by complex interactions between light-absorbing and light-scattering structures, but for many signals, potential interactions between different light-interacting components have yet to be tested. Butterfly wings, for example, are thin enough that their two sides may not be optically isolated. We tested whether ventral wing scales of the Mormon fritillary, Speyeria mormonia, affect the appearance of dorsal orange patches, which are thought to be involved in sexual signaling. Using reflectance spectroscopy, we found that ventral scales, either silvered or non-silvered, make dorsal orange patches significantly brighter, with the silvered scales having the greater effect. Computational modeling indicates that both types of ventral scale enhance the chromatic perceptual signal of dorsal orange patches, with only the silvered scales also enhancing their achromatic perceptual signal. A lack of optical independence between the two sides of the wings of S. mormonia implies that the wing surfaces of butterflies have intertwined signaling functions and evolutionary histories.

Supine hypotensive syndrome of pregnancy: A review of current knowledge.

Since the first description of supine hypotensive syndrome in the 1950s, its potentially detrimental effects on otherwise healthy women during late pregnancy have become a persistent challenge in obstetric practice. Establishing a 15° left lateral tilt during labour and caesarean section is a fundamental principle of obstetric care, universally adopted and upheld by current guidelines and recommendations. Reassessment of the original landmark studies in the light of current physiological and anatomical knowledge questions adherence to this standard in clinical practice. The modern practice of providing vasopressor support during caesarean delivery under neuraxial anaesthesia appears to negate any potential negative effects of a maternal full supine position. Recent MRI studies provide evidence as to the cause of supine hypotension and the physiological effects of different maternal positions at term. This review highlights current data on the acute supine hypotensive syndrome in contrast to traditional knowledge and established practice.

Panoramic spatial vision in the bay scallop Argopecten irradians.

We have a growing understanding of the light-sensing organs and light-influenced behaviours of animals with distributed visual systems, but we have yet to learn how these animals convert visual input into behavioural output. It has been suggested they consolidate visual information early in their sensory-motor pathways, resulting in them being able to detect visual cues (spatial resolution) without being able to locate them (spatial vision). To explore how an animal with dozens of eyes processes visual information, we analysed the responses of the bay scallop Argopecten irradians to both static and rotating visual stimuli. We found A. irradians distinguish between static visual stimuli in different locations by directing their sensory tentacles towards them and were more likely to point their extended tentacles towards larger visual stimuli. We also found that scallops track rotating stimuli with individual tentacles and with rotating waves of tentacle extension. Our results show, to our knowledge for the first time that scallops have both spatial resolution and spatial vision, indicating their sensory-motor circuits include neural representations of their visual surroundings. Exploring a wide range of animals with distributed visual systems will help us learn the different ways non-cephalized animals convert sensory input into behavioural output.

Safety and efficacy of tetrastarches in surgery and trauma: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Hydroxyethyl starch (HES) 130 is a frequently used fluid to replace intravascular losses during surgery or trauma. In the past years, several trials performed in critically ill patients have raised questions regarding the safety of this product. Our aim in this meta-analysis was to evaluate the safety and efficacy of 6% HES during surgery and in trauma. METHODS: This systematic review and meta-analysis was registered at PROSPERO (CRD42018100379). We included 85 fully published articles from 1980 to June 2018 according to the protocol and three additional recent articles up to June 2020 in English, French, German, and Spanish reporting on prospective, randomised, and controlled clinical trials applying volume therapy with HES 130/0.4 or HES 130/0.42, including combinations with crystalloids, to patients undergoing surgery. Comparators were albumin, gelatin, and crystalloids only. A meta-analysis could not be performed for the two trauma studies as there was only one study that reported data on endpoints of interest. RESULTS: Surgical patients treated with HES had lower postoperative serum creatinine (P<0.001) and showed no differences in renal dysfunction, renal failure, or renal replacement therapy. Although there was practically no further difference in the colloids albumin or gelatin, the use of HES improved haemodynamic stability, reduced need for vasopressors (P<0.001), and decreased length of hospital stay (P<0.001) compared with the use of crystalloids alone. CONCLUSIONS: HES was shown to be safe and efficacious in the perioperative setting. Results of the present meta-analysis suggest that when used with adequate indication, a combination of intravenous fluid therapy with crystalloids and volume replacement with HES as colloid has clinically beneficial effects over using crystalloids only.

Functional testing of tranexamic acid effects in patients undergoing elective orthopaedic surgery.

Tranexamic acid (TXA) can reduce blood loss and transfusion rates in orthopaedic surgery. In this regard, a new viscoelastometric test (TPA-test, ClotPro), enables the monitoring of TXA effects. This prospective observational study evaluated and correlated TXA plasma concentrations (cTXA) following intravenous and oral administration in patients undergoing elective orthopaedic surgery with lysis variables of TPA-test. Blood samples of 42 patients were evaluated before TXA application and 2, 6, 12, 24 and 48 h afterwards. TPA-test was used to determine lysis time (LT) as well as maximum lysis (ML) and cTXA was measured using Ultra-High-Performance-Liquid-Chromatography/Mass-Spectrometry. Data are presented as median (min-max). LTTPA-test and MLTPA-test correlated with cTXA (r = 0.9456/r = 0.5362; p < 0.0001). 2 h after intravenous TXA administration all samples showed complete lysis inhibition (LTTPA-test prolongation: T1: 217 s (161-529) vs. T2: 4500 s (4500-4500);p < 0.0001), whereas after oral application high intraindividual variability was observed as some samples showed only moderate changes in LTTPA-test (T1: 236 s (180-360) vs. T2: 4500 s (460-4500); p < 0.0001). Nevertheless, statistically LTTPA-test did not differ between groups. MLTPA-test differed 2 h after application (i.v.: 9.0% (5-14) vs. oral: 31% (8-97); p = 0.0081). In 17/21 samples after oral and 0/21 samples after intravenous administration cTXA was < 10 µg ml-1 2 h after application. TPA-test correlated with cTXA. MLTPA-test differed between intravenous and oral application 2 h after application. Most patients with oral application had TXA plasma concentration < 10 µg ml-1. The duration of action did not differ between intravenous and oral application. Additional studies evaluating clinical outcomes and side-effects based on individualized TXA prophylaxis/therapy are required.

Treatment of spinal anaesthesia-induced hypotension with cafedrine/theodrenaline versus ephedrine during caesarean section: Results from HYPOTENS, a national, multicentre, prospective, noninterventional study.

BACKGROUND: In Germany, hypotension induced by spinal anaesthesia is commonly treated with a combination of cafedrine hydrochloride (C, 200 mg) and theodrenaline hydrochloride (T, 10 mg) in 2 ml. We compared the effectiveness of C/T with ephedrine. OBJECTIVES: The primary objectives were to assess the speed of onset and the ability to restore blood pressure without an increase in heart rate. Secondary objectives were to evaluate maternal/foetal outcomes and the number of required additional boluses or other additional measures. DESIGN: HYPOTENS was a national, multicentre, prospective, open-label, two-armed, noninterventional study comparing C/T with ephedrine in two prospectively defined cohorts. This study relates to the cohort of patients receiving spinal anaesthesia for caesarean section. SETTING: German hospitals using either C/T or ephedrine in their routine clinical practice. PATIENTS: Women aged at least 18 years receiving spinal anaesthesia for caesarean section. INTERVENTIONS: Bolus administration of C/T or ephedrine at the discretion of the attending anaesthesiologist. MAIN OUTCOME MEASURES: Endpoints within 15 min after initial administration of C/T or ephedrine were area under the curve between the observed SBP and the minimum target SBP; and incidence of newly occurring heart rate of at least 100 beats min-1. RESULTS: Although effective blood pressure stabilisation was achieved with both treatments, this effect was faster and more pronounced with C/T (P < 0.0001). The incidence of tachycardia and changes in heart rate were higher with ephedrine (P < 0.01). Fewer additional boluses (P < 0.01) were required with C/T. Although favourable neonatal outcomes were reported in both groups, base deficit and lactate values were greater with ephedrine (P < 0.01). Physician satisfaction was higher with C/T. CONCLUSIONS: After C/T, tachycardia was not a problem, providing an advantage over ephedrine. Fewer additional boluses were required with C/T, suggesting greater effectiveness. An increased base deficit with ephedrine suggests reduced oxygen supply or increased demands in foetal circulation. TRIALS REGISTRATION: Clinicaltrials.gov: NCT02893241, German Clinical Trials Register: DRKS00010740.

[Fluid and Volume Therapy with Crystalloid and Colloidal Infusion Solutions]. / Flüssigkeits- und Volumentherapie mit kristalloiden und kolloidalen Lösungen.

A rational infusion therapy orchestrates fluid- and volume therapy based on the individual indication and situation. The principle of fluid replacement is to substitute ongoing fluid losses such as insensible perspiration and urine output or to treat dehydration with balanced crystalloid solutions. Volume therapy in contrast is the quick restoration of intravascular losses such as an acute blood loss through application of balanced colloids or crystalloids. The goal of volume therapy is to maintain normal cardiac output and oxygen delivery by restoring intravascular normovolemia and cardiac preload. Whether colloid or crystalloid infusions are most suitable for volume therapy remains unclear. Most trials in this field are either underpowered or used colloids in inadequate situations, patients and amounts. Two major trials from the European Society of Anaesthesiology and Intensive Care (ESAIC) are underway that seem promising to provide evidence in this emotional debate.

A snapping shrimp has the fastest vision of any aquatic animal.

Animals use their sensory systems to sample information from their environments. The physiological properties of sensory systems differ, leading animals to perceive their environments in different ways. For example, eyes have different temporal sampling rates, with faster-sampling eyes able to resolve faster-moving scenes. Eyes can also have different dynamic ranges. For every eye, there is a light level below which vision is unreliable because of an insufficient signal-to-noise ratio and a light level above which the photoreceptors are saturated. Here, we report that the eyes of the snapping shrimp Alpheus heterochaelis have a temporal sampling rate of at least 160 Hz, making them the fastest-sampling eyes ever described in an aquatic animal. Fast-sampling eyes help flying animals detect objects moving across their retinas at high angular velocities. A. heterochaelis are fast-moving animals that live in turbid, structurally complex oyster reefs and their fast-sampling eyes, like those of flying animals, may help them detect objects moving rapidly across their retinas. We also report that the eyes of A. heterochaelis have a broad dynamic range that spans conditions from late twilight (approx. 1 lux) to direct sunlight (approx. 100 000 lux), a finding consistent with the circatidal activity patterns of this shallow-dwelling species.

Natriuretic Peptides as a Prognostic Marker for Delirium in Cardiac Surgery-A Pilot Study.

Background and Objectives: Delirium is a common and major complication subsequent to cardiac surgery. Despite scientific efforts, there are no parameters which reliably predict postoperative delirium. In delirium pathology, natriuretic peptides (NPs) interfere with the blood-brain barrier and thus promote delirium. Therefore, we aimed to assess whether NPs may predict postoperative delirium and long-term outcomes. Materials and Methods: To evaluate the predictive value of NPs for delirium we retrospectively analyzed data from a prospective, randomized study for serum levels of atrial natriuretic peptide (ANP) and the precursor of C-type natriuretic peptide (NT-proCNP) in patients undergoing coronary artery bypass grafting (CABG) with or without cardiopulmonary bypass (off-pump coronary bypass grafting; OPCAB). Delirium was assessed by a validated chart-based method. Long-term outcomes were assessed 10 years after surgery by a telephone interview. Results: The overall incidence of delirium in the total cohort was 48% regardless of the surgical approach (CABG vs. OPCAB). Serum ANP levels >64.6 pg/mL predicted delirium with a sensitivity (95% confidence interval) of 100% (75.3-100) and specificity of 42.9% (17.7-71.1). Serum NT-proCNP levels >1.7 pg/mL predicted delirium with a sensitivity (95% confidence interval) of 92.3% (64.0-99.8) and specificity of 42.9% (17.7-71.1). Both NPs could not predict postoperative survival or long-term cognitive decline. Conclusions: We found a positive correlation between delirium and preoperative plasma levels of ANP and NT-proCNP. A well-powered and prospective study might identify NPs as biomarkers indicating the risk of delirium and postoperative cognitive decline in patients at risk for postoperative delirium.

[Antihypotensive drugs in cesarean sections : Treatment of arterial hypotension with ephedrine, phenylephrine and Akrinor® (cafedrine/theodrenaline) during cesarean sections with spinal anesthesia]. / Antihypotensiva bei Kaiserschnittentbindungen : Behandlung der arteriellen Hypotension mit Ephedrin, Phenylephrin und Akrinor® (Cafedrin/Theodrenalin) im Rahmen von Kaiserschnittentbindungen in Spinalanästhesie.

BACKGROUND: Arterial hypotension is a frequent complication following spinal anesthesia for cesarean sections. A fast treatment is necessary to maintain the well-being of the mother and to avoid deficiencies in the intrauterine supply to the child. OBJECTIVE: The aim of this analysis was to evaluate the effects of the most frequently used vasoactive substances for treatment of hypotension in patients undergoing cesarean sections in Germany, i.e. ephedrine (E), phenylephrine (P) and Akrinor (A, cafedrine/theodrenaline), a 20:1 combination of cafedrine and theodrenaline. METHODS: A retrospective single center analysis of 772 patients (16-50 years old) with arterial hypotension following spinal anesthesia for cesarean section and requiring treatment with vasoactive substances (July 2012-April 2017) was carried out. In the three observation periods the respective current clinical standard treatment of E, P or A was applied. The primary end-points were changes in maternal hemodynamics, pH and base excess (BE) in the child and the resulting blood pressure values. The statistical analysis plan of the study was registered in the German registry for clinical trials (DRKS-ID: DRKS00012520). RESULTS: The initial blood pressure before the intervention was comparable in all three groups, with no clinically relevant differences between the individual groups. In the course of anesthesia the largest blood pressure decrease as well as the largest resulting increase after the intervention were found in group A. In group P there was an increased need for an alternative catecholamine in comparison to the other two groups (P : 13 patients, 3.7%, E: 5 patients, 3.3% and A: 0 patients (0%), p  0.007). Differences were detected in the BE of the child (mean E: -1.36, P : -2.03, A: -2.57, p  0.0001) and the incidence of bradycardia requiring drug intervention (E: 0.7%, P : 5.4%, A: 1.9%, p = 0.007). No significant differences were found for the arterial pH of the child and APGAR scores. CONCLUSION: The differences of the individual vasoactive substances seemed to be much smaller than one would expect based on the results of randomized clinical trials. The incidence and extent of bradycardia and neonatal acidosis were much lower than previously reported. The determined differences seemed to have no major clinical relevance. Although the A group required less bolus administrations and seemed to be the most potent substance, the results imply that the assessment of the effects of vasoactive substances should not be carried out without consideration of the accompanying measures.

Evidence for spatial vision in Chiton tuberculatus, a chiton with eyespots.

To better understand relationships between the structures and functions of the distributed visual systems of chitons, we compare how morphological differences between the light-sensing structures of these animals relate to their visually guided behaviors. All chitons have sensory organs - termed aesthetes - embedded within their protective shell plates. In some species, the aesthetes are interspersed with small, image-forming eyes. In other species, the aesthetes are paired with pigmented eyespots. Previously, we compared the visually influenced behaviors of chitons with aesthetes to those of chitons with both aesthetes and eyes. Here, we characterize the visually influenced behaviors of chitons with aesthetes and eyespots. We find that chitons with eyespots engage in behaviors consistent with spatial vision, but appear to use spatial vision for different tasks than chitons with eyes. Unlike chitons with eyes, Chiton tuberculatus and C. marmoratus fail to distinguish between sudden appearances of overhead objects and equivalent, uniform changes in light levels. We also find that C. tuberculatus orients to static objects with angular sizes as small as 10 deg. Thus, C. tuberculatus demonstrates spatial resolution that is at least as fine as that demonstrated by chitons with eyes. The eyespots of Chiton are smaller and more numerous than the eyes found in other chitons and they are separated by angles of <0.5 deg, suggesting that the light-influenced behaviors of Chiton may be more accurately predicted by the network properties of their distributed visual system than by the structural properties of their individual light-detecting organs.

Preemptive volume therapy to prevent hemodynamic changes caused by the beach chair position: hydroxyethyl starch 130/0.4 versus Ringer's acetate-a controlled randomized trial.

BACKGROUND: Hemodynamic instability frequently occurs in beach chair positioning for surgery, putting patients at risk for cerebral adverse events. This study examined whether preoperative volume loading with crystalloids alone or with a crystalloid-colloid combination can prevent hemodynamic changes that may be causative for unfavorable neurologic outcomes. METHODS: The study randomly assigned 43 adult patients undergoing shoulder surgery to 3 study groups. Each group received an infusion of 500 mL of Ringer's acetate between induction of anesthesia and being placed in the beach chair position. The crystalloid group received an additional bolus of 1000 mL Ringer's acetate. The hydroxyethyl starch group was administered an additional bolus of 500 mL of 6% hydroxyethyl starch 130/0.4. Hemodynamic monitoring was accomplished via an esophageal Doppler probe. Cerebral oxygen saturation was examined with near-infrared spectroscopy. Changes in stroke volume variation between the prone and beach chair positions were defined as the primary outcome parameter. Secondary outcomes were changes in cardiac output and cerebral oxygen saturation. RESULTS: The control group was prematurely stopped after enrollment of 4 patients because of adverse events. In the hydroxyethyl starch group, stroke volume variation remained constant during positioning maneuvers (P = .35), whereas a significant increase was observed in the Ringer's acetate group (P < .01; P = .014 for intergroup comparison). This was also valid for changes in cardiac output. Cerebral oxygen saturation significantly decreased in both groups. CONCLUSIONS: Preprocedural boluses of 500 mL of 6% hydroxyethyl starch 130/0.4 as well as 1000 mL of Ringer's acetate were efficient in preserving hemodynamic conditions during beach chair position.

Vascular Endothelial Dysfunction during Cardiac Surgery: On-Pump versus Off-Pump Coronary Surgery.

BACKGROUND: Cardiac surgery often causes ischemia and development of a systemic inflammatory response syndrome, which impairs vascular barrier function, normally maintained by the endothelial cell line and the endothelial glycocalyx (EG). The EG normally covers and protects healthy endothelial cells throughout the vasculature. The aim of the present study was to assess the disruption of the cellular part of the microvascular barrier by determining parameters of endothelial cell activation known to influence and reflect cell-cell junctional integrity. Particular attention was placed on angiopoietins and their important effects on endothelial gap junctions. Furthermore, comparative measurements were undertaken in patients undergoing on- and off-pump cardiac surgery, the latter group presumably experiencing less ischemic stress. METHODS: 30 patients undergoing elective coronary artery bypass surgery were assigned to the conventional coronary artery bypass (CCAB) group (n = 15) or the off-pump coronary artery bypass grafting (OPCAB) group (n = 15). Blood samples were obtained for measuring angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), vascular endothelial (VE)-cadherin, and endocan at various time points. RESULTS: There were significant increases in all measured parameters in both study groups versus the respective basal values. Maximal increases were as follows: Ang-1: CCAB +220%, OPCAB +166%, p < 0.05 each; Ang-2: CCAB +150%, OPCAB +20%, p < 0.05 each; VE-cadherin: CCAB +87%, OPCAB +66%, p < 0.05 each; endocan: CCAB +323%, OPCAB +72%, p < 0.05 each. CONCLUSION: The present study demonstrates the activation of endothelial cells, shedding of cell-cell contacts and a potential intrinsic counterregulation by Ang-1 and endocan in patients undergoing major cardiac surgery. Quantitatively greater deviations of parameters in the CCAB than in the OPCAB group suggest a relation between the occurrence of ischemia/reperfusion and the extent of endothelial activation.

The endothelial glycocalyx and perioperative lung injury.

PURPOSE OF REVIEW: Ventilator-induced lung injury is a major contributor to perioperative lung injury. The end-expiratory lung volume, regional lung overdistension, and tidal recruitment are known to be the main factors causing subsequent alveolar damage and inflammation. The alveolar-capillary membrane including the endothelial glycocalyx as an integral part of the vascular endothelium seems to play a major role in different kinds of lung injury. RECENT FINDINGS: Recent studies underline the pivotal importance of the endothelial glycocalyx in lung injury. The glycocalyx regulates and modulates plasma endothelial cell interactions. Several triggers are known to deteriorate the gylcocalyx such as fluid overload, ischemia, and TRALI. The clinical manifestation is inflammation, capillary leak, and edema formation. Breakdown of the endothelial gylcocalyx is of gaining importance in the context of one-lung ventilation, known to be a major risk factor for postoperative lung injury. Studies suggest that volatile anesthetics may have a protective influence on the endothelial glycocalyx of pulmonary capillaries and reduce ischemia-reperfusion injury. This might be of clinical relevance for postoperative outcome. SUMMARY: This review focuses on the involvement of the pulmonary endothelial glycocalyx in the context of perioperative lung injury. The pathophysiological mechanisms and trigger factors of glycocalyx deterioration are discussed, and prevention strategies are taken into consideration.

[Update in Obstetric Anesthesia - Tried and Trusted Methods, Controversies and New Perspectives]. / Geburtshilfliche Anästhesie: Altbewährtes, Kontroversen und neue Perspektiven ­ Teil 2.

Since 1975, a plethora of lectures within the context of annual meetings relevant for the clinical care has been summarized in "what's new in obstetric anesthesia" by the society for Obstetric anesthesia and Perinatology which can be recommended to everyone interested in anaesthesiology in the delivery room. After the death of Gerard W. Ostheimer, Professor of Anaesthesiology at Brigham and Women's Hospital in Boston, Massachusetts, it became renamed the Gerard W. Ostheimer "what's new in obstetric anesthesia" lecture to honor his contributions to regional anesthesia and obstetric anaesthesia. Each year the event held by selected professional representatives and their imprint in leading anesthesia journals give insight into a critical appraisal of recent literature and the possible consequences for - but not only - the anaesthetic delivery room practice.A similar event has been established in Germany for more than 16 years (first event on April 1, 2000, most recently held on February 27, 2016, in Munich): the obstetrical anesthesia symposium of the academic working group "regional anesthesia and obstetrical anesthesia" [1], [2]."Evergreens" or "hot topics" with regard to anaesthesiological delivery room practice are presented and discussed regularly. The lectures often reveal the subtle change of the issues being debated much earlier than traditional textbook chapters do. This manuscript summarizes important findings from the last symposium held in 2016. Part I focuses on relevant causes for maternal morbidity and mortality as well as preventive measures, pregnancy in obese patients and sepsis in obstetric anaesthesia. Part II addresses established standards and new perspectives in the direct obstetric setting regarding epidural analgesia, post-dural puncture headache, anaesthesia and analgesia during and after caesarean section, haemodynamic monitoring during cesarean section and postpartum haemorrhage.

[Update in Obstetric Anesthesia: Tried and Trusted Methods, Controversies and New Perspectives - Part 1]. / Geburtshilfliche Anästhesie: Altbewährtes, Kontroversen und neue Perspektiven ­ Teil 1.

Since 1975, a plethora of lectures within the context of annual meetings relevant for the clinical care has been summarized in "what's new in obstetric anesthesia" by the Society for Obstetric Anesthesia and Perinatology which can be recommended to everyone interested in anaesthesiology in the delivery room. After the death of Gerard W. Ostheimer, Professor of Anaesthesiology at Brigham and Women's Hospital in Boston, Massachusetts, it became renamed the Gerard W. Ostheimer "what's new in obstetric anesthesia" lecture to honor his contributions to regional anesthesia and obstetric anaesthesia. Each year the event held by selected professional representatives and their imprint in leading anesthesia journals give insight into a critical appraisal of recent literature and the possible consequences for - but not only - the anaesthetic delivery room practice.A similar event has been established in Germany for more than 16 years: the obstetrical anesthesia symposium of the academic working group "regional anesthesia and obstetrical anesthesia" 1, 2."Evergreens" or "hot topics" with regard to anaesthesiological delivery room practice are presented and discussed regularly. The lectures often reveal the subtle change of the issues being debated much earlier than traditional textbook chapters do. This manuscript summarizes important findings from the last symposium held in 2016. Part I focuses on relevant causes for maternal morbidity and mortality as well as preventive measures, pregnancy in obese patients and sepsis in obstetric anaesthesia. Part II addresses established standards and new perspectives in the direct obstetric setting regarding epidural analgesia, post-dural puncture headache, anaesthesia and analgesia during and after caesarean section, haemodynamic monitoring during cesarean section and postpartum haemorrhage.

Regulation of blood flow and volume exchange across the microcirculation.

Oxygen delivery to cells is the basic prerequisite of life. Within the human body, an ingenious oxygen delivery system, comprising steps of convection and diffusion from the upper airways via the lungs and the cardiovascular system to the microvascular area, bridges the gap between oxygen in the outside airspace and the interstitial space around the cells. However, the complexity of this evolutionary development makes us prone to pathophysiological problems. While those problems related to respiration and macrohemodynamics have already been successfully addressed by modern medicine, the pathophysiology of the microcirculation is still often a closed book in daily practice. Nevertheless, here as well, profound physiological understanding is the only key to rational therapeutic decisions. The prime guarantor of tissue oxygenation is tissue blood flow. Therefore, on the premise of intact macrohemodynamics, the microcirculation has three major responsibilities: 1) providing access for oxygenated blood to the tissues and appropriate return of volume; 2) maintaining global tissue flood flow, even in the face of changes in central blood pressure; and 3) linking local blood flow to local metabolic needs. It is an intriguing concept of nature to do this mainly by local regulatory mechanisms, impacting primarily on flow resistance, be this via endothelial or direct smooth muscle actions. The final goal of microvascular blood flow per unit of time is to ensure the needed exchange of substances between tissue and blood compartments. The two principle means of accomplishing this are diffusion and filtration. While simple diffusion is the quantitatively most important form of capillary exchange activity for the respiratory gases, water flux across the blood-brain barrier is facilitated via preformed specialized channels, the aquaporines. Beyond that, the vascular barrier is practically nowhere completely tight for water, with paracellular filtration giving rise to generally low but permanent fluid flux outwards into the interstitial space at the microvascular high pressure segment. At the more leaky venular aspect, both filtration and diffusion allow for bidirectional passage of water, nutrients, and waste products. We are just beginning to appreciate that a major factor for maintaining tissue fluid homeostasis appears to be the integrity of the endothelial glycocalyx.

Degradation of the endothelial glycocalyx in clinical settings: searching for the sheddases.

The endothelial glycocalyx has a profound influence at the vascular wall on the transmission of shear stress, on the maintenance of a selective permeability barrier and a low hydraulic conductivity, and on attenuating firm adhesion of blood leukocytes and platelets. Major constituents of the glycocalyx, including syndecans, heparan sulphates and hyaluronan, are shed from the endothelial surface under various acute and chronic clinical conditions, the best characterized being ischaemia and hypoxia, sepsis and inflammation, atherosclerosis, diabetes, renal disease and haemorrhagic viral infections. Damage has also been detected by in vivo microscopic techniques. Matrix metalloproteases may shed syndecans and heparanase, released from activated mast cells, cleaves heparan sulphates from core proteins. According to new data, not only hyaluronidase but also the serine proteases thrombin, elastase, proteinase 3 and plasminogen, as well as cathepsin B lead to loss of hyaluronan from the endothelial surface layer, suggesting a wide array of potentially destructive conditions. Appropriately, pharmacological agents such as inhibitors of inflammation, antithrombin and inhibitors of metalloproteases display potential to attenuate shedding of the glycocalyx in various experimental models. Also, plasma components, especially albumin, stabilize the glycocalyx and contribute to the endothelial surface layer. Though symptoms of the above listed diseases and conditions correlate with sequelae expected from disturbance of the endothelial glycocalyx (oedema, inflammation, leukocyte and platelet adhesion, low reflow), therapeutic studies to prove a causal connection have yet to be designed. With respect to studies on humans, some clinical evidence exists for benefits from application of sulodexide, a preparation delivering precursors of the glycocalyx constituent heparan sulphate. At present, the simplest option for protecting the glycocalyx seems to be to ensure an adequate level of albumin. However, also in this case, definite proof of causality needs to be delivered.