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.

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.

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.

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.

A facility for the analysis of the electronic structures of solids and their surfaces by synchrotron radiation photoelectron spectroscopy.

A synchrotron radiation beamline in the photon energy range of 18-240 eV and an electron spectroscopy end station have been constructed at the 3 GeV Diamond Light Source storage ring. The instrument features a variable polarisation undulator, a high resolution monochromator, a re-focussing system to form a beam spot of 50 × 50 µm2, and an end station for angle-resolved photoelectron spectroscopy (ARPES) including a 6-degrees-of-freedom cryogenic sample manipulator. The beamline design and its performance allow for a highly productive and precise use of the ARPES technique at an energy resolution of 10-15 meV for fast k-space mapping studies with a photon flux up to 2 ⋅ 1013 ph/s and well below 3 meV for high resolution spectra.

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.

[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.

The IL-33 receptor (ST2) regulates early IL-13 production in fungus-induced allergic airway inflammation.

Allergic airway inflammation (AAI) in response to environmental antigens is an increasing medical problem, especially in the Western world. Type 2 interleukins (IL) are central in the pathological response but their importance and cellular source(s) often rely on the particular allergen. Here, we highlight the cellular sources and regulation of the prototypic type 2 cytokine, IL-13, during the establishment of AAI in a fungal infection model using Cryptococcus neoformans. IL-13 reporter mice revealed a rapid onset of IL-13 competence within innate lymphoid cells type 2 (ILC2) and IL-33R(+) T helper (Th) cells. ILC2 showed IL-33-dependent proliferation upon infection and significant IL-13 production. Th cells essentially required IL-33 to become either GATA3(+) or GATA3(+)/Foxp3(+) hybrids. GATA3(+) Th cells almost exclusively contributed to IL-13 production but hybrid GATA3(+)/Foxp3(+) Th cells did not. In addition, alveolar macrophages upregulated the IL-33R and subsequently acquired a phenotype of alternative activation (Ym1(+), FIZZ1(+), and arginase-1(+)) linked to type 2 immunity. Absence of adaptive immunity in rag2(-/-) mice resulted in attenuated AAI, revealing the need for Th2 cells for full AAI development. Taken together, in pulmonary cryptococcosis ILC2 and GATA3(+) Th2 cells produce early IL-13 largely IL-33R-dependent, thereby promoting goblet cell metaplasia, pulmonary eosinophilia, and alternative activation of alveolar macrophages.

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.

[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.

T1/ST2 promotes T helper 2 cell activation and polyfunctionality in bronchopulmonary mycosis.

Interleukin (IL)-33 enhances T helper (Th)2 immunity via its receptor T1/ST2. Infection with the yeast-like pathogen Cryptococcus neoformans is usually controlled by a Th1-mediated immune response. The mechanisms responsible for nonprotective Th2 immunity leading to allergic inflammation in pulmonary cryptococcosis are still not fully understood. Using a murine pulmonary model of C. neoformans infection, we report that T1/ST2 expression correlates with the intensity of Th2 activation, as demonstrated by the expression of CD25 and CD44 and downregulation of CD62L. Antigen-specific T1/ST2(+) Th cells are the primary source of the Th2 cytokines IL-5 and IL-13 as compared with wild-type T1/ST2(-) Th cells or Th cells from T1/ST2(-/-) mice. In addition, T1/ST2(+) Th cells almost exclusively contain bi- and trifunctional Th2 cytokine-producing Th cells compared with T1/ST2(-) Th cells or Th cells from T1/ST2(-/-) mice. Finally, T1/ST2-driven Th2 development resulted in defective pulmonary fungal control. These data demonstrate that T1/ST2 directs Th2 cell activation and polyfunctionality in allergic bronchopulmonary mycosis.

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.

Lack of IL-4 receptor expression on T helper cells reduces T helper 2 cell polyfunctionality and confers resistance in allergic bronchopulmonary mycosis.

T helper (Th)1 and Th2 cells play decisive roles in the regulation of resistance vs. susceptibility to pulmonary cryptococcosis. To study the function of interleukin (IL)-4 receptor (IL-4R) on Th cells in pulmonary cryptococcosis, we infected mice specifically lacking IL-4Rα on CD4(+) T cells (Lck(Cre)IL-4Rα(-/lox) mice) and IL-4Rα(-/lox) controls. Lck(Cre)IL-4Rα(-/lox) mice developed enhanced resistance accompanied by reduced pulmonary allergic inflammation and diminished production of the Th2 cytokines IL-4, IL-5, and IL-13 as compared with IL-4Rα(-/lox) mice. Polyfunctional antigen-specific Th2 cells producing simultaneously two or three Th2 cytokines were reduced in infected Lck(Cre)IL-4Rα(-/lox) mice, pointing to a critical role of polyfunctional Th2 cells for disease progression. Reduced Th2 polyfunctionality was associated with fewer pulmonary alternatively activated macrophages. This work is the first direct evidence for a critical contribution of the IL-4R on Th cells to Th2-dependent susceptibility during allergic bronchopulmonary mycosis. Moreover, the data demonstrate that the quality of the Th2 response has an impact on type 2 inflammation. The analysis of polyfunctional Th2 cells may be useful for monitoring the course of the disease.

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.

[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.

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.