Anaesthetic efficacy and postinduction hypotension with remimazolam compared with propofol: a multicentre randomised controlled trial.

Remimazolam, a short-acting benzodiazepine, may be used for induction and maintenance of total intravenous anaesthesia, but its role in the management of patients with multiple comorbidities remains unclear. In this phase 3 randomised controlled trial, we compared the anaesthetic efficacy and the incidence of postinduction hypotension during total intravenous anaesthesia with remimazolam vs. propofol. A total of 365 patients (ASA physical status 3 or 4) scheduled for elective surgery were assigned randomly to receive total intravenous anaesthesia with remimazolam (n = 270) or propofol (n = 95). Primary outcome was anaesthetic effect, quantified as the percentage of time with Narcotrend® Index values ≤ 60, during surgery (skin incision to last skin suture), with a non-inferiority margin of -10%. Secondary outcome was the incidence of postinduction hypotensive events. Mean (SD) percentage of time with Narcotrend Index values ≤ 60 during surgery across all patients receiving remimazolam (93% (20.7)) was non-inferior to propofol (99% (4.2)), mean difference (97.5%CI) -6.28% (-8.89-infinite); p = 0.003. Mean (SD) number of postinduction hypotension events was 62 (38.1) and 71 (41.1) for patients allocated to the remimazolam and propofol groups, respectively; p = 0.015. Noradrenaline administration events (requirement for a bolus and/or infusion) were also lower in patients allocated to remimazolam compared with propofol (14 (13.5) vs. 20 (14.6), respectively; p < 0.001). In conclusion, in patients who were ASA physical status 3 or 4, the anaesthetic effect of remimazolam was non-inferior to propofol.

Clinical validation and accuracy testing of a radiographic decision aid for unicondylar knee arthroplasty patient selection in midterm follow-up.

PURPOSE: The purpose of this study was to examine the predictive value concerning clinical outcome and implant survival, as well as the accuracy of individual tests of a recently published radiographic decision aid for unicondylar knee arthroplasty indication findings. METHODS: In the retrospective part of the study, 98 consecutive patients who had undergone unicondylar knee arthroplasty (Phase 3 Oxford medial UKA) were included, using revision questionnaires, as well as the Forgotten Joint Score-12 (FJS-12) and Knee Osteoarthritis Outcome Score (KOOS) and analysed for suitability of the radiographic decision aid. Inappropriate and appropriate indications were then compared concerning the clinical outcome and implant survival. The prospective part of the study assessed the accuracy of the decision aid's radiographic tests (varus and valgus stress views, true lateral view and skyline view), and included 90 patients. Definition as appropriate for UKA procedure included medial bone-on-bone situation in varus stress views, full-thickness lateral cartilage and functional medial collateral ligament in valgus stress views, functional anterior cruciate ligament (ACL) in true lateral views and absence of lateral facet osteoarthritis with bone loss in skyline views. Pre-operative radiographic assessment with respect to the decision aid was then compared with intraoperative articular conditions. The clinical outcome was analysed using non-parametric tests (Mann-Whitney U), and revision rates were compared using the Fisher's exact test. Accuracy assessment included calculations of the sensitivity, specificity, negative predictive value and positive predictive value. A p value < 0.05 was considered statistically significant. RESULTS: Appropriate unicondylar knee arthroplasty with respect to the decision aid showed a significantly lower revision rate compared to inappropriate unicondylar knee arthroplasty (7.3% vs. 50.0%, p < 0.0001), as well as higher clinical outcome scores (FJS-12: 53.13 vs. 31.25, p = 0.041 and KOOS-QDL: 68.75 vs. 50.0, p = 0.036). The overall sensitivity (70.1%) and specificity (76.2%) for the radiographic decision aid was comparably low, which was essentially based on false negative cases (22.7%) regarding medial bone-to-bone conditions. CONCLUSION: The radiographic decision aid is a helpful tool to predict clinical outcome and implant survival of mobile-bearing unicondylar knee arthroplasty. Strict use of the radiographic decision aid may lead to increased exclusion of appropriate patients with unicondylar knee arthroplasty implantation.

Descriptive characteristics and in-hospital mortality of critically bleeding patients requiring massive transfusion: results from the Australian and New Zealand Massive Transfusion Registry.

BACKGROUND AND OBJECTIVES: Critically bleeding patients requiring massive transfusion (MT) are clinically challenging, and limited data exist to support management decisions. This study describes patient characteristics, transfusion support and clinical outcomes from the Australian and New Zealand (NZ) Massive Transfusion Registry (ANZ-MTR). MATERIALS AND METHODS: Retrospective, cohort study of all adult patients receiving MT (≥5 units red blood cells [RBC] in 4 h) at participating ANZ-MTR hospitals, 2011-2015. Mortality information was collected from the Australian National Death Index and NZ Ministry of Health. Associations between patient characteristics and outcomes were modelled using logistic regression. RESULTS: A total of 3560 MT cases were identified. For in-hospital deaths, cardiothoracic surgery was the most frequent bleeding context (24·5%) followed by trauma (18·3%). Age (OR = 1·03; 95% CI: 1·02-1·04), more comorbidities (OR = 1·14; 95% CI: 1·09-1·21), larger volume of RBC in first 24 h from MT onset (OR = 1·04; 95% CI: 1·02-1·06), higher platelet to RBC ratio at 4 h (OR = 2·76; 95% CI: 1·14-6·65) and higher activated partial thromboplastin time (OR = 1·02; 95% CI: 1·01-1·03) were associated with in-hospital mortality. CONCLUSION: Patients with more comorbidities, older age, traumatic or surgical bleeding or requiring more blood components had higher in-hospital mortality. These findings provide a basis to evaluate and monitor practice relating to optimal use of blood products, variation in transfusion practices and patient outcomes, and also enable benchmarking of hospital performance for management of MT in specific patient groups.

New Antarctic Gravity Anomaly Grid for Enhanced Geodetic and Geophysical Studies in Antarctica.

Gravity surveying is challenging in Antarctica because of its hostile environment and inaccessibility. Nevertheless, many ground-based, airborne and shipborne gravity campaigns have been completed by the geophysical and geodetic communities since the 1980s. We present the first modern Antarctic-wide gravity data compilation derived from 13 million data points covering an area of 10 million km2, which corresponds to 73% coverage of the continent. The remove-compute-restore technique was applied for gridding, which facilitated levelling of the different gravity datasets with respect to an Earth Gravity Model derived from satellite data alone. The resulting free-air and Bouguer gravity anomaly grids of 10 km resolution are publicly available. These grids will enable new high-resolution combined Earth Gravity Models to be derived and represent a major step forward towards solving the geodetic polar data gap problem. They provide a new tool to investigate continental-scale lithospheric structure and geological evolution of Antarctica.

[Management of anesthesia in endovascular interventions]. / Anästhesiologisches Management bei endovaskulären Gefäßeingriffen.

Cardiovascular diseases are one of the leading causes of morbidity and mortality in Germany. In these patients, the high-risk profile necessitates an interdisciplinary and multimodal approach to treatment. Endovascular interventions and vascular surgery have become established as an important element of this strategy in the past; however, the different anatomical localizations of pathological vascular alterations make it necessary to use a wide spectrum of procedural options and methods; therefore, the requirements for management of anesthesia are variable and necessitate a differentiated approach. Endovascular procedures can be carried out with the patient under general or regional anesthesia (RA); however, in the currently available literature there is no evidence for an advantage of RA over general anesthesia regarding morbidity and mortality, although a reduction in pulmonary complications could be found for some endovascular interventions. Epidural and spinal RA procedures should be carefully considered with respect to the risk-benefit ratio and consideration of the recent guidelines on anesthesia against the background of the current study situation and the regular use of therapy with anticoagulants. The following article elucidates the specific characteristics of anesthesia management as exemplified by some selected endovascular interventions.

[Diffuse pulmonary meningotheliomatosis]. / Diffuse pulmonale Meningotheliomatose.

In two patients with bilateral micronodular pulmonary changes a diffuse pulmonary meningotheliomatosis was found. A 73-year-old woman presented with bilateral disseminated miliary pulmonary nodules as a radiological incidental finding. The surgical lung biopsy showed multiple tiny nodular proliferations meningothelial-like cells, corresponding "minute pulmonary meningothelial-like nodules", MPMN. A 60-year-old lady with similar radiological findings showed also proliferations of meningothelial-like cells in a transbronchial cryo-biopsy. These lesions are well known to pathologists as curious isolated incidental findings on histological examination of lung specimens. The here described diffuse form of these changes is very rare; its knowledge is important for the differential diagnosis with neoplastic proliferations and other diffuse parenchymal diseases of the lung. This rare diagnosis is made on histological grounds and is also possible in transbronchial biopsies when careful correlation with clinical and radiological data, knowledge of the entity and adequate specimens are provided.

Maternal and newborn vitamin D status and its impact on food allergy development in the German LINA cohort study.

BACKGROUND: Vitamin D levels are known to be associated with atopic disease development; however, existing data are controversial. The aim of this study was to investigate whether corresponding maternal and cord blood vitamin D levels are associated with atopic outcomes in early infancy. METHODS: Within the LINA cohort study (Lifestyle and environmental factors and their Influence on Newborns Allergy risk), 25(OH)D was measured in blood samples of 378 mother-child pairs during pregnancy and at birth. Information about children's atopic manifestations during the first 2 years of life was obtained from questionnaires filled out by the parents during pregnancy and annually thereafter. Cord blood regulatory T cells (Treg) were detected by methylation-specific PCR using a Treg-specific demethylated region in the FOXP3 gene. RESULTS: The median maternal 25(OH)D(3) level was 22.19 ng/ml (IQR 14.40-31.19 ng/ml); the median cord blood 25(OH)D(3) 10.95 ng/ml (6.99-17.39 ng/ml). A high correlation was seen between maternal and cord blood 25(OH)D(3) levels, both showing a seasonal distribution. Maternal and cord blood 25(OH)D(3) was positively associated with children's risk for food allergy within the first 2 years. Further, higher maternal 25(OH)D(3) resulted in a higher risk for sensitization against food allergens at the age of two. Cord blood 25(OH)D(3) levels were negatively correlated with regulatory T cell numbers. CONCLUSION: Our study demonstrates that high vitamin D levels in pregnancy and at birth may contribute to a higher risk for food allergy and therefore argues against vitamin D supplement to protect against allergy.

Genome-wide, large-scale production of mutant mice by ENU mutagenesis.

In the post-genome era, the mouse will have a major role as a model system for functional genome analysis. This requires a large number of mutants similar to the collections available from other model organisms such as Drosophila melanogaster and Caenorhabditis elegans. Here we report on a systematic, genome-wide, mutagenesis screen in mice. As part of the German Human Genome Project, we have undertaken a large-scale ENU-mutagenesis screen for dominant mutations and a limited screen for recessive mutations. In screening over 14,000 mice for a large number of clinically relevant parameters, we recovered 182 mouse mutants for a variety of phenotypes. In addition, 247 variant mouse mutants are currently in genetic confirmation testing and will result in additional new mutant lines. This mutagenesis screen, along with the screen described in the accompanying paper, leads to a significant increase in the number of mouse models available to the scientific community. Our mutant lines are freely accessible to non-commercial users (for information, see http://www.gsf.de/ieg/groups/enu-mouse.html).

Single chest drain is not inferior to double chest drain after robotic esophagectomy: a propensity score-matched analysis.

Background: Chest drain management has a significant influence on postoperative recovery after robot-assisted minimally invasive esophagectomy (RAMIE). The use of chest drains increases postoperative pain by irritating intercostal nerves and hinders patients from early postoperative mobilization and recovery. To our knowledge, no study has investigated the use of two vs. one intercostal chest drains after RAMIE. Methods: This retrospective cohort study evaluated patients undergoing elective RAMIE with gastric conduit pull-up and intrathoracic anastomosis. Patients were divided into two groups according to placement of one (11/2020-08/2022) or two (08/2018-11/2020) chest drains. Propensity score matching was performed in a 1:1 ratio, and the incidences of overall and pulmonary complications, drainage-associated re-interventions, radiological diagnostics, analgesic use, and length of hospital stay were compared between single drain and double drain groups. Results: During the study period, 194 patients underwent RAMIE. Twenty-two patients were included after propensity score matching in the single and double chest drain group, respectively. Time until removal of the last chest drain [postoperative day (POD) 6.7 ± 4.4 vs. POD 9.4 ± 2.7, p = 0.004] and intensive care unit stay (4.2 ± 5.1 days vs. 5.3 ± 3.5 days, p = 0.01) were significantly shorter in the single drain group. Overall and pulmonary complications, drainage-associated events, re-interventions, number of diagnostic imaging, analgesic use, and length of hospital stay were comparable between both groups. Conclusion: This study is the first to demonstrate the safety of single intercostal chest drain use and, at least, non-inferiority to double chest drains in terms of perioperative complications after RAMIE.

Drainless robot-assisted minimally invasive oesophagectomy-randomized controlled trial (RESPECT).

BACKGROUND: The purpose of this randomized trial is to evaluate the early removal of postoperative drains after robot-assisted minimally invasive oesophagectomy (RAMIE). Evidence is lacking about feasibility, associated pain, recovery, and morbidity. METHODS/DESIGN: This is a randomized controlled multicentric trial involving 72 patients undergoing RAMIE. Patients will be allocated into two groups. The "intervention" group consists of 36 patients. In this group, abdominal and chest drains are removed 3 h after the end of surgery in the absence of contraindications. The control group consists of 36 patients with conventional chest drain management. These drains are removed during the further postoperative course according to a standard algorithm. The primary objective is to investigate whether postoperative pain measured by NRS on the second postoperative day can be significantly reduced in the intervention group. Secondary endpoints are the intensity of pain during the first week, analgesic use, number of postoperative chest X-ray and CT scans, interventions, postoperative mobilization (steps per day as measured with an activity tracker), postoperative morbidity and mortality. DISCUSSION: Until now, there have been no trials investigating different intraoperative chest drain strategies in patients undergoing RAMIE for oesophageal cancer with regard to perioperative complications until discharge. Minimally invasive approaches combined with enhanced recovery after surgery (ERAS) protocols lower morbidity but still include the insertion of chest drains. Reduction and early removal have been proposed after pulmonary surgery but not after RAMIE. The study concept is based on our own experience and the promising current results of the RAMIE procedure. Therefore, the presented randomized controlled trial will provide statistical evidence of the effectiveness and feasibility of the "drainless" RAMIE. TRIAL REGISTRATION: ClinicalTrials.gov NCT05553795. Registered on 23 September 2022.

Cell-mediated transgenesis in rabbits: chimeric and nuclear transfer animals.

The ability to perform precise genetic engineering such as gene targeting in rabbits would benefit biomedical research by enabling, for example, the generation of genetically defined rabbit models of human diseases. This has so far not been possible because of the lack of functional rabbit embryonic stem cells and the high fetal and perinatal mortality associated with rabbit somatic cell nuclear transfer. We examined cultured pluripotent and multipotent cells for their ability to support the production of viable animals. Rabbit putative embryonic stem (ES) cells were derived and shown capable of in vitro and in vivo pluripotent differentiation. We report the first live born ES-derived rabbit chimera. Rabbit mesenchymal stem cells (MSCs) were derived from bone marrow, and multipotent differentiation was demonstrated in vitro. Nuclear transfer was carried out with both cell types, and embryo development was assessed in vitro and in vivo. Rabbit MSCs were markedly more successful than ES cells as nuclear donors. MSCs were transfected with fluorescent reporter gene constructs and assessed for nuclear transfer competence. Transfected MSCs supported development with similar efficiency as normal MSCs and resulted in the first live cloned rabbits from genetically manipulated MSCs. Reactivation of fluorescence reporter gene expression in reconstructed embryos was investigated as a means of identifying viable embryos in vitro but was not a reliable predictor. We also examined serial nuclear transfer as a means of rescuing dead animals.

Determination of rubella virus-specific cell-mediated immunity using IFN gamma-ELISpot.

Immunity to rubella virus (RV) is conventionally determined by measuring specific immunoglobulin G (IgG). However, several individuals may be considered immune despite undetectable antibody levels. In the present study RV-specific interferon-gamma (IFN gamma)-ELISpot and rubella-IgG-ELISA were compared in 75 young adults aged between 20 and 30 years. In a subgroup, not only rubella-like particles (RLP), but also HPV77 rubella vaccine derived antigen was used in IFN gamma-ELISpot. The results from both, ELISA and ELISpot were independent of previous encounter to RV (vaccination, exanthematous disease, or childhood infection). There was no difference between RLP and RV vaccine antigen in IFN gamma-ELISpot response, and there was no correlation between IFN gamma-ELISpot and RV-specific IgG levels. IFN gamma-producing cells were found in 78.7% of all tested persons, and 83.8% of them were positive in ELISA. In almost all individuals seronegative for RV antibody, IFN gamma-producing cells were detected. Considering both humoral and cell-mediated immune responses, a positive RV immune reaction was seen in 98.6%. The results indicate that the IFN gamma-ELISpot can provide valuable additional information in seronegative individuals.

Electrical transport properties of single undoped and n-type doped InN nanowires.

Electrical transport properties of undoped and n-type doped InN nanowires grown by molecular beam epitaxy were studied by current-voltage and back-gate field-effect transistor measurements. The current-voltage characteristics show ohmic behavior in the temperature range between 4 and 300 K. Down to about 120 K a linear decrease in resistance with temperature is observed. The investigation of a large number of nanowires revealed for undoped as well as doped wires an approximately linear relation between the normalized conductance and diameter for wires with a diameter below 100 nm. This shows that the main conduction takes place in the tubular surface accumulation layer of the wires. In contrast, for doped wires with a diameter larger than 100 nm a quadratic dependence of conduction on the diameter was found, which is attributed to bulk conductance as the main contribution. The successful doping of the wires is confirmed by an enhanced conduction and by the results of the back-gate field-effect transistor measurements.

[Tracheostoma. Handling and complications]. / Tracheostoma. Handhabung und Komplikationen.

Tracheostomy has gained importance due to recent developments in critical care medicine. This procedure is the most frequent surgical intervention on intensive care wards. Indications for tracheostomy (conventional versus dilatational) should consider the duration of the need for a tracheal cannula. The decision for one of the types of tracheostomy may have a relevant impact on the airway management and the rehabilitation of swallowing, because these are dependent on state of the tracheostoma and its subsequent maintenance. Selection of the appropriate cannula helps to avoid complications and improve patient comfort. To minimize the risks during tracheostomy, skills and expertise on the management of life- threatening complications are necessary. Early and late complications can be detected by regular examination of the tracheostoma which may help to repress complications in an early stage and can improve the long term outcome.

Evaluation of PTR-ToF-MS as a tool to track the behavior of hop-derived compounds during the fermentation of beer.

Hop-derived volatile organic compounds (VOCs) play an important role in the flavor and aroma of beer, despite making up a small percentage of the overall profile. To understand the changes happening during fermentation, proton transfer reaction-time of flight-mass spectrometry (PTR-ToF-MS) was applied for the first time in brewing science to directly measure the changes in hop-derived VOCs during the fermentation of four different worts containing one of two aroma hops in combination with one of two yeast biotypes. PTR-ToF-MS successfully detected and tracked mass-to-charge ratios (m/z) arising from interactions between the different yeast strains and the hop cultivars. Differences were observed in the dynamic VOC profiles between different beer treatments for m/z such as m/z 145.121 (ethyl hexanoate) and m/z 173.153 (isoamyl isovalerate or ethyl octanoate). The ability to monitor changes in VOCs during fermentation provides valuable information on the priority of production and transformation reactions by yeast.

Disease Lesion Mimicry Caused by Mutations in the Rust Resistance Gene rp1.

The rp1 locus of maize controls race-specific resistance to the common rust fungus Puccinia sorghi. Four mutant or recombinant Rp1 alleles (rp1-NC3, Rp1-D21, Rp1-MD19, and Rp1-Kr1N) were identified. They condition necrotic phenotypes in the absence of the rust pathogen. These Rp1 lesion mimics fall into three different phenotypic classes: (1) The rp1-NC3 and Rp1-D21 alleles require rust infection or other biotic stimulus to initiate necrotic lesions. These alleles react strongly to all maize rust biotypes tested and also to nonhost rusts. (2) The Rp1-MD19 allele, which has a similar phenotype, also requires a biotic stimulus to initiate lesions. However, Rp1-MD19 shows the race specificity of the Rp1-D gene. (3) The Rp1-Kr1N allele specifies a diffuse necrotic phenotype in the absence of any biotic stimulus and a race-specific reaction when inoculated with maize rust.

Shared decision making and self-management in multiple sclerosis--a consequence of evidence.

Shared decision making is increasingly recognised as the ideal model of patient-physician communication especially in chronic diseases with partially effective treatments such as multiple sclerosis (MS). Since 2001, we studied prerequisites for patient participation in decision making as well as the effects of evidence-based patient information on decision making processes in MS. In pre-studies we found that 80% of MS patients demand autonomous roles in treatment decisions which contrasts to a poor knowledge of risks. On the other hand MS patients are not disturbed by evidence-based, balanced complex information. MS patients can understand this kind of information and are able to transfer new abilities to other situations. Major information interests were related to symptom alleviation, diagnostic procedures and prognosis. Currently, we study the effects of a 4 hour education programme on relapse management versus an information leaflet as controls in 150 RR MS patients in a randomised-controlled trial. In a second trial including 280 MS patients we study the effects of an evidence-based decision aid on immunotherapy on decisional role preference and performance in the patient physician encounter. Results at the end of 2006 will show to which extent patient education with a focus on evidence-based patient information influences participation in the decision making process. Assuming that patient education programmes will enhance self-management abilities and the sense of control over the disease with enhanced quality of life and well-being, further modules covering all aspects of MS are to be developed.

Informed shared decision making in multiple sclerosis--inevitable or impossible?

Patients and health authorities increasingly claim active roles in health care decision making processes. As immune therapies in MS are partially effective MS is a prototypic condition for a shared decision making process. The treatment of acute relapses and the initiation, change or withdrawal of so called disease-modifying treatments are key decisions in MS management. We developed two decision aids following the phased approach of the framework of increasing evidence for complex interventions for these key decisions. In prestudies we found that 80% of MS patients demand autonomous roles in treatment decisions which contrasts with a poor knowledge of risks. On the other hand MS patients are not disturbed by evidence-based, balanced complex information. MS patients do understand this kind of information and are able to transfer new abilities to other situations. Currently we study the effects of a 4-hour education programme on relapse management versus an information leaflet in controls in 150 MS patients. In a second trial with n=298 MS patients we study the effects of an evidence-based patient information on immunotherapy on decisional role preference and performance in the patient physician encounter. Results in early 2007 will show to which extent patient education with a focus on evidence-based patient information influences participation in the decision making process.