Phosphodiesterase 3 inhibitors do not influence lactate kinetics and clinical outcomes in patients with septic shock: A multicentre cohort study.

PURPOSE: We investigated the association between the administration of phosphodiesterase 3 inhibitors (PDE3i) and lactate kinetics, resolution of organ failure, ICU and hospital length of stay (LOS) and hospital mortality in a retrospective cohort of patients with septic shock and persistently elevated lactate concentrations. MATERIAL AND METHODS: Patients with septic shock and two arterial lactate concentrations ≥4 mmol/L with at least 4 h between measurements were eligible. Clinical data of the first four days of admission were collected in an online database. For each patient, the area between the actual lactate concentrations and 2.2 mmol/L (AUClact2.2), was calculated for three days. RESULTS: Data on 229 patients from 10 hospitals were collected, of whom 123 received PDE3i (54%). First, a linear multivariate model was developed to predict AUClact2.2 (R2 = 0.57). Adding PDE3i as a cofactor did not affect R2. Second, 60 patients receiving PDE3i at any time between days 0 and 2 were compared to 60 propensity matched no-PDE3i patients. Third, 30 patients who received PDE3i from ICU admission to day 3 were compared to 30 propensity-matched no-PDE3i patients. These analyses showed no differences in AUClact2.2, SOFA scores, ICU or hospital LOS or hospital mortality between treatment groups. CONCLUSIONS: No association was found between the administration of PDE3i and lactate kinetics, resolution of organ failure, ICU or hospital LOS or hospital mortality.

Wolf Creek XVII part 3: Automated cardiac arrest diagnosis.

Introduction: Automated cardiac arrest diagnosis offers the possibility to significantly shorten the interval between onset of out-of-hospital cardiac arrest (OHCA) and notification of EMS, providing the opportunity for earlier resuscitation and possibly increased survival. Methods: Automated cardiac arrest diagnosis was one of six focus topics for the Wolf Creek XVII Conference held on June 14-17 2023 in Ann Arbor, Michigan, USA. Conference invitees included international thought leaders and scientists in the field of cardiac arrest resuscitation from academia and industry. Participants submitted via online survey knowledge gaps, barriers to translation and research priorities for each focus topic. Expert panels used the survey results and their own perspectives and insights to create and present a preliminary unranked list for each category that was debated, revised and ranked by all attendees to identify the top 5 for each category. Results: Top knowledge gaps include the accuracy of automated OHCA detection technologies and the feasibility and reliability of automated EMS activation. The main barriers to translation are the risk of false positives potentially overburdening EMS, development and application costs of technology and the challenge of integrating new technology in EMS IT systems. The top research priorities are large-scale evaluation studies to measure real world performance and user research regarding the willingness to adopt these technologies. Conclusion: Automated cardiac arrest diagnosis has the potential to significantly impact time to resuscitation and survival of OHCA because it could convert unwitnessed events into witnessed events. Validation and feasibility studies are needed. The specificity of the technology must be high not to overburden limited EMS resources. If adequate event classification is achieved, future research could shift toward event prediction, focusing on identifying potential digital biomarkers and signatures of imminent cardiac arrest. Implementation could be challenging due to high costs of development, regulatory considerations and instantiation logistics.

In multi electron beam systems, "Neighbours Matter".

In the Multi beam source (MBS) of our Multi Beam Scanning Electron Microscope (MBSEM), an aperture lens array (ALA) splits the emission cone of the Schottky field emitter into multiple beamlets. When the apertures in the ALA are close to each other, the ALA can introduce aberrations to these beamlets through the electrostatic interaction of neighbouring apertures with each aperture's lens field. When the apertures are arranged in a square grid pattern, the aberration causes fourfold astigmatism. The effect on the beam spot is analyzed through a combination of 3D simulations and experimental validation. To counterbalance the fourfold astigmatism, a correction scheme is proposed in which a slightly non-round profile is applied to the aperture lenses.

Smartwatch based automatic detection of out-of-hospital cardiac arrest: Study rationale and protocol of the HEART-SAFE project.

Out-of-hospital cardiac arrest (OHCA) is a leading cause of mortality. Immediate detection and treatment are of paramount importance for survival and good quality of life. The first link in the 'chain of survival' after OHCA - the early recognition and alerting of emergency medical services - is at the same time the weakest link as it entirely depends on witnesses. About one half of OHCA cases are unwitnessed, and victims of unwitnessed OHCA have virtually no chance of survival with good neurologic outcome. Also in case of a witnessed cardiac arrest, alerting of emergency medical services is often delayed for several minutes. Therefore, a technological solution to automatically detect cardiac arrests and to instantly trigger an emergency response has the potential to save thousands of lives per year and to greatly improve neurologic recovery and quality of life in survivors. The HEART-SAFE consortium, consisting of two academic centres and three companies in the Netherlands, collaborates to develop and implement a technical solution to reliably detect OHCA based on sensor signals derived from commercially available smartwatches using artificial intelligence. In this manuscript, we describe the rationale, the envisioned solution, as well as a protocol outline of the work packages involved in the development of the technology.

Autonomous patient consent for anaesthesia without preoperative consultation: a qualitative feasibility study including low-risk procedures.

Background: Informed consent for anaesthesia is mandatory and requires provision of information and subsequent consent during consultation between anaesthesiologist and patient. Although information can be provided in an electronic format, it is unknown whether this a valid substitute for a consultation. We explored whether provision of digital information is equivalent to oral consultation and whether it enables patients to give electronic informed consent (e-consent) for anaesthesia. Methods: Qualitative feasibility study using semi-structured interviews in 20 low-risk adults scheduled for minor surgery under general anaesthesia or procedural sedation at a university hospital. Data were analysed using a thematic content analysis approach. During the interviews, patients followed an application that provides information and subsequent e-consenting. Results: The mean age was 50 yr and patients had good digital skills. Fifteen patients (75%) had previous experience of anaesthesia. The digital application provided enough information for all patients, but eight (40%) preferred consultation with an anaesthesiologist, mainly for personal contact. Patients had different information needs, with previous experiences leading to lower information needs. Nineteen patients had sufficient information to consent autonomously. Most patients considered separate anaesthesia consent superfluous to the surgical consent. Conclusion: The digital application provided sufficient information and patients valued the information offered and the advantage of processing information at their own pace. This information made patients feel empowered to autonomously consent to anaesthesia without consultation. Remarkably, consent for anaesthesia was considered unimportant, because patients felt they had 'no choice' if they wanted to undergo surgery.

Spectroscopic reflectometry of mirror surfaces during plasma exposure.

An in situ spectroscopic reflectometry system has been built to investigate the evolution of the specular reflectivity spectrum of ITER first mirror samples during plasma exposure. Results are presented for three different types of molybdenum mirror samples that were exposed to deuterium plasma, including single crystalline, nanocrystalline, and polycrystalline molybdenum. The results show good agreement with ex situ measurements of the reflectivity spectrum before and after exposure and extend the results obtained in previous experiments.

The effect of ankle foot orthosis stiffness on the energy cost of walking: a simulation study.

BACKGROUND: In stroke and multiple sclerosis patients, gait is frequently hampered by a reduced ability to push-off with the ankle caused by weakness of the plantar-flexor muscles. To enhance ankle push-off and to decrease the high energy cost of walking, spring-like carbon-composite Ankle Foot Orthoses are frequently prescribed. However, it is unknown what Ankle Foot Orthoses stiffness should be used to obtain the most efficient gait. The aim of this simulation study was to gain insights into the effect of variation in Ankle Foot Orthosis stiffness on the amount of energy stored in the Ankle Foot Orthosis and the energy cost of walking. METHODS: We developed a two-dimensional forward-dynamic walking model with a passive spring at the ankle representing the Ankle Foot Orthosis and two constant torques at the hip for propulsion. We varied Ankle Foot Orthosis stiffness while keeping speed and step length constant. FINDINGS: We found an optimal stiffness, at which the energy delivered at the hip joint was minimal. Energy cost decreased with increasing energy storage in the ankle foot orthosis, but the most efficient gait did not occur with maximal energy storage. With maximum storage, push-off occurred too late to reduce the impact of the contralateral leg with the floor. Maximum return prior to foot strike was also suboptimal, as push-off occurred too early and its effects were subsequently counteracted by gravity. The optimal Ankle Foot Orthosis stiffness resulted in significant push-off timed just prior to foot strike and led to greater ankle plantar-flexion velocity just before contralateral foot strike. INTERPRETATION: Our results suggest that patient energy cost might be reduced by the proper choice of Ankle Foot Orthosis stiffness.

Mechanical analysis of the preferred strategy selection in human stumble recovery.

We use simple walking models, based on mechanical principles, to study the preferred strategy selection in human stumble recovery. Humans typically apply an elevating strategy in response to a stumble in early swing and midswing, for which the perturbed step is lengthened in a continuation of the original step. A lowering strategy is executed for stumbles occurring at midswing or late swing, for which the perturbed swing foot is immediately placed on the ground and the recovery is executed in the subsequent step. There is no clear understanding of why either strategy is preferred over the other. We hypothesize that the human strategy preference is the result of an attempt to minimize the cost of successful recovery. We evaluate five hypothesized measures for recovery cost, focusing on the energetic cost of active recovery limb placement. We determine all hypothesized cost measures as a function of the chosen recovery strategy and the timing of the stumble during gait. Minimization of the cost measures based on the required torque, impulse, power and torque/time results in a humanlike strategy preference. The cost measure based on swing work does not predict a favorable strategy as a function of the gait phase.

[Synopsis of various electrophysiological tests in early glaucoma diagnosis--temporal and spatiotemporal contrast sensitivity, light- and color-contrast pattern-reversal electroretinogram, blue-yellow VEP]. / Synopsis verschiedener sinnesphysiologischer Untersuchungen in der Glaukom-Frühdiagnose--Zeitliche und örtlich-zeitliche Kontrastempfindlichkeit, Helligkeits- und Farbkontrast-Muster-ERG, Blau-auf-gelb-VEP.

BACKGROUND: Of the three glaucoma-defining criteria intraocular pressure, optic-nerve damage, and visual field damage, the latter is a late symptom. Therefore, in order to improve an early sensory diagnosis, new tests are necessary. It is the aim of the present paper to test new sensory methods, to rank them in an order of sensitivity, and to base them on possible pathophysiological mechanisms. PATIENTS AND METHODS: The tests were carried out in subjects of the Erlangen Glaucoma registry: Normals, patients with ocular hypertension, and patients with open-angle glaucoma without or with field defects. The tests are designed to preferentially probe the function of different groups of ganglion cells. Psychophysical methods: Temporal contrast sensitivity in a ganzfeld as "Erlangen flicker test" and spatio-temporal contrast sensitivity to test Magno-cell function. Electrophysiological methods: Pattern-reversal electroretinogram with a luminance-contrast pattern to test Magno-cell function, color-contrast pattern electroretinogram for Parvo-cell function, and blue-on-yellow visual evoked potential to test the "blue-sensitive" pathway. RESULTS: The most sensitive test is the temp.CS, it is significantly reduced in OHT (p < 0.01). The spatio-temp.CS is reduced in perimetric stages (p < 0.01). The BY-VEP is altered in the preperimetric stage (p < 0.01), the PR-ERG in perimetric stages (p < 0.01). The CC-ERG is reduced in even later stages. These results are in agreement with the hypothesis that tests selective for non-redundant neurons are of early diagnostic value. Multivariate analyses increase the early diagnostic value when different functions are tested in combination. CONCLUSIONS: When a particular test is taylored to the the special needs of certain groups of ganglion cells sensory defects can be observed before the occurrence of optic-nerve damage (OHT). The most sensitive psychophysical test is the "Erlangen flicker test" which is a screening test selective for M cells. The most sensitive electrophysiological test is the BY-VEP testing the blue-sensitive ganglion cells.

Quantitative analysis of visual field and optic disk in glaucoma: retinal nerve fiber bundle-associated analysis.

BACKGROUND: A study was performed to evaluate whether visual field analysis using a perimetric nerve fiber bundle map gives information additional to global visual field indices and cumulative defect curves for early glaucoma diagnosis. METHODS: One hundred and four control subjects, 124 patients with ocular hypertension (OHT), 97 patients with high-tension glaucoma without visual field defects (preHTG) and 91 patients with open-angle glaucoma with visual field defects [30 low-tension glaucoma (LTG), 61 high-tension glaucoma (HTG)] were included in this study. Correlation analyses were performed between (a) global visual field indices and total neuroretinal rim (NRR) area; (b) local mean values of four visual field areas and the NRR area of the corresponding four optic disk sectors; and (c) local mean values of 10 perimetric nerve fiber bundles (PNFB 1-10) according to Weber and Ulrich (1991) and the four optic disk sectors. The correlations were adjusted for global mean defect and total NRR. RESULTS: There were no significant correlations between NRR area and visual field in control subjects or in patients with OHT or preHTG for all three analyses. Significant correlations were found between the global visual field indices and the total NRR area for LTG and HTG. Significant correlations between local mean defects and NRR area of corresponding optic disk sectors were found only in LTG for the superior and inferior visual field area and the PNFB covering these areas. CONCLUSION: The method used for visual field analysis and sectorization of the optic disk does not give additional information on visual field defects in patients with normal global visual field indices and a normal cumulative defect curve. The nerve fiber bundle-related visual field analysis allows the topographical determination and quantification of glaucomatous damage.

Migraine and tension headache in high-pressure and normal-pressure glaucoma.

PURPOSE: To analyze the association of normal-pressure glaucoma and migraine. METHODS: In a prospective study, 154 patients with glaucoma (56 normal-pressure subgroup and 98 high-pressure glaucoma subgroup), 55 patients with ocular hypertension, and 75 control subjects were analyzed by means of a standardized questionnaire based on International Headache Society criteria. RESULTS: According to the questionnaire, 46 patients (17%) were classified as suffering from migraine and 20 (7%) from tension headache (episodic and chronic). The prevalence of headache, migraine, and tension headache did not vary significantly among control subjects, patients with ocular hypertension, and patients with glaucoma, but migraine was significantly more common in patients with normal-pressure glaucoma (28%) compared with control subjects (12%; P<.05) and patients with high-pressure glaucoma (10%; P<.01). CONCLUSION: The results suggest an association of normal-pressure glaucoma and migraine and a potential, common vascular etiology of both diseases.

The kinematic total knee arthroplasty. A 10- to 15-year follow-up and survival analysis.

In 86 patients 102 consecutive cemented Kinematic total knee arthroplasties were reviewed 10-15 years after surgery to determine the clinical and radiographic results and to assess the survival rate. The average age of the 65 female and 21 male patients at the time of surgery was 63 years. Forty-six knees were affected by rheumatoid arthritis (RA), 46 by osteoarthritis (OA), 7 by haemophilic arthropathy and 3 by osteonecrosis. One patient (1 knee) was lost to follow-up, and 31 patients (38 knees) died. Eleven knees had been revised for deep infection (4), wear (4), malposition (2) or persistent pain (1). Fifty-two knees were examined at an average follow-up period of 12 years. The mean Knee Society Score of 89 points was the same for RA and AO knees. Also, 92% of the knees caused no pain or only occasional mild pain. There were no cases of aseptic loosening of any component. Progressive radiolucent lines were not seen on the follow-up radiographs (43 knees, mean follow-up 12 years) The 10- and 14-year survival rates with revision as the end-point were 90% (confidence interval, CI: 81%-95%) and 82% (CI: 67%-92%), respectively. In the worst case scenario, with knees lost to follow-up and knees with moderate pain considered as failures, the 10- and 14-year survival rates were 80% (CI: 69%-88%) and 62% (CI: 46%-77%), respectively. The Kinematic total knee arthroplasty yields equally good long-term results in patients with RA and those with OA. Deep infection and wear were the main reasons for revision.

Multivariate approach for quantification of morphologic and functional damage in glaucoma.

PURPOSE: To determine the usefulness of confirmatory factor analysis in examination of morphometric, electrophysiological, and psychophysical quantitative methods that measure the extent of global glaucomatous damage without referring to a preselected gold standard. METHODS: In a cross-sectional clinical study, 406 eyes of 203 glaucoma patients and 200 eyes of 100 normal control subjects 18 to 70 years old underwent optic disc morphometry, automated perimetry, measurement of temporal contrast sensitivity by a full-field flicker test, blue-on-yellow visually evoked potential (VEP), and black-and-white pattern-reversal electroretinogram (ERG). Diagnosis of glaucoma was based on a qualitative classification of the optic nerve head and retinal nerve fiber layer independent of intraocular pressure and visual field. Confirmatory factor analysis was performed in the patient group as a whole and in a subgroup showing moderate to advanced glaucomatous optic nerve head damage. RESULTS: The confirmatory factor analysis models explained the data satisfactorily (P > 0.18, all patients; P > 0.34, subgroup). Global glaucomatous damage was quantified best by the mean defect of automated perimetry (r = 0.81; r = 0.87), followed by the area of the neuroretinal rim (r = 0.64; r = 0.73), the full-field flicker test (r = 0.59; r = 0.65), the pattern-reversal ERG amplitude (r = 0.54; r = 0.55), and the VEP peak time (r = 0.55; r = 0.54). CONCLUSIONS: Confirmatory factor analysis allows quantification of the validity of established and new procedures that measure global glaucomatous damage using cross-sectional data. The results are not dependent on the preselection of a specific gold standard. Psychophysical testing and morphometry quantified glaucomatous damage best, compared with electrophysiological procedures.

A multivariate sensory model in glaucoma diagnosis.

PURPOSE: To evaluate whether the combination of two psychophysical and two electrophysiological procedures improves diagnostic validity compared with single procedures. METHODS: In a clinical study, 73 patients with glaucoma from the University Eye Hospital in Erlangen and 122 healthy control subjects from the university staff, ranging in age from 19 to 62 years, underwent measurement of temporal contrast sensitivity using a full-field flicker test, spatiotemporal contrast sensitivity, blue-on-yellow visual evoked potential (VEP), and a black-and-white, pattern-reversal electroretinogram. Diagnostic reference criteria included applanation tonometry, optic disc morphometry, and automated perimetry. Sensitivity was determined univariately with a fixed specificity of 80% and in a multivariate approach using logistic regression analysis. The classification rate was estimated using the leaving-one-out method. The correlation with intraocular pressure, visual field defects, and optic nerve defects was determined. RESULTS: Contrast sensitivity measurements and the blue-on-yellow pattern-onset VEP showed comparable sensitivity (85%, 84%, and 85%) with 80% specificity, and a pattern-reversal electroretinogram showed lower sensitivity (64%). The first three methods contributed independent information to a diagnostic score. This score improved sensitivity to 94%, with a specificity of 89%. All procedures moderately correlated with the neuroretinal rim area of the optic disc (r=0.32-0.46). The psychophysical tests showed a higher correlation with visual field defects (r > 0.5) than the electrophysiological tests (r < 0.3). CONCLUSIONS: The multivariate approach substantially increased the diagnostic validity compared with single procedures. This was probably because the diagnostic procedures under investigation tested different aspects of visual function.

[Use of a new anomaloscope test in diagnosis of glaucoma]. / Anwendung eines neuen Anomaloskop-Tests in der Glaukomdiagnostik.

BACKGROUND: The Color Vision Meter 712 (CVM) is a new automatic computerized anomaloscope relying on both the Rayleigh and the Moreland equation. In the present study the diagnostic value of Color Vision Meter was examined in glaucoma for the first time and was compared with the Farnsworth 100 hue test. PATIENTS AND METHODS: 33 normals, 15 patients with ocular hypertension (OHT) and a heterogenic group of 31 glaucoma patients were tested with the Nagel anomaloscope, the Color Vision Meter 712 and the Farnsworth 100 hue test. The following determinations were made in all subjects: 1. Anomalous quotient of the Rayleigh equation of the Nagel anomaloscope and of the Color Vision Meter, 2. Mean tritan score of 100 hue test, 3. The matching range, mid matching point, and anomalous quotient of the Moreland equation with the Color Vision Meter. RESULTS: While in the OHT group only the matching range of the Moreland equation was enlarged, all three variables (matching range, mid matching point and anomalous quotient) of the Moreland equation were significantly changed in the glaucoma group. The mean tritan score of the 100 hue test showed in the OHT group only a slight difference compared to normals, and in the glaucoma group a low significance and a low sensitivity. The matching range of the Moreland equation seems to be most useful with a sensitivity of 87.1% and a specificity of 93.6%. CONCLUSION: Our results show that the new anomaloscope Color Vision Meter 712 should be considered as a quick screening test for the examination of blue-color vision disturbances in glaucoma because of its higher sensitivity, its easier use for examiner and patients, and its shortened examination time (5 min per equation).