Introduction. Pteridines, such as neopterin, biopterin, and tetrahydrobiopterin (BH4), may be involved in depression pathophysiology owing to their links to immune-inflammatory response, oxidative and nitrosative stress, and monoaminergic transmission. Nonetheless, studies assessing pteridines in depression are inconsistent. We conducted a systematic review and meta-analysis of observational studies comparing blood pteridine concentrations between subjects with depression and healthy controls (HCs). Methods. We searched Embase, MEDLINE, and PsycInfo for articles indexed through November 2021. Study quality was appraised, evaluating age and gender comparability between groups, sample representativeness, and methods to assess depression. Random-effects meta-analyses were carried out, generating pooled standardized mean differences (SMDs). Heterogeneity across studies was estimated using the I2 statistic. Results. Twenty-four studies, involving 3075 subjects, were included. Individuals with depression showed blood neopterin concentrations higher than HCs (k = 19; SMD = 0.36; p < 0.001) with moderate heterogeneity across studies (I2 = 58.2%). No moderating role of age, gender, or type of blood sample was found. Sensitivity analyses showed no impact of inconsistency and quality of studies on findings. Neopterin concentrations were higher among individuals with major depressive disorder compared to HCs (SMD = 0.44; p < 0.001). This held true also when considering only drug-free subjects (SMD = 0.68; p = 0.003). No differences in biopterin concentrations were found between subjects with depression and HCs (k = 5; SMD = –0.35; p = 0.086), though this result was limited by inconsistency of findings (I2 = 77.9%) and quality of studies. Finally, no sufficient data were available for a meta-analysis on BH4. Conclusions. As a whole, our work partly supports the hypothesis of an imbalance of pteridine metabolism in depression.
As the current biotherapeutic market is dominated by antibodies, the design of different antibody formats, like bispecific antibodies, is critical to the advancement of the field. In contrast to monovalent antibodies, which consist of two identical antigen-binding sites, bispecific antibodies can target two different epitopes by containing two different antigen-binding sites. Thus, the rise of new formats as successful therapeutics has reignited the interest in advancing and facilitating the efficient production of bispecific antibodies. Here, we investigate the influence of point mutations in the antigen-binding site, the paratope, on heavy and light chain pairing preferences by using molecular dynamics simulations. In agreement with experiments, we find that specific residues in the antibody variable domain (Fv), i.e., the complementarity-determining region (CDR) L3 and H3 loops, determine heavy and light chain pairing preferences. Excitingly, we observe substantial population shifts in CDR-H3 and CDR-L3 loop conformations in solution accompanied by a decrease in bispecific IgG yield. These conformational changes in the CDR3 loops induced by point mutations also influence all other CDR loop conformations and consequentially result in different CDR loop states in solution. However, besides their effect on the obtained CDR loop ensembles, point mutations also lead to distinct interaction patterns in the VH-VL interface. By comparing the interaction patterns among all investigated variants, we observe specific contacts in the interface that drive heavy and light chain pairing. Thus, these findings have broad implications in the field of antibody engineering and design because they provide a mechanistic understanding of antibody interfaces, by identifying critical factors driving the pairing preferences, and thus can help to advance the design of bispecific antibodies.
Purpose: To assess the technical outcome and local tumor control of multi-probe stereotactic radiofrequency ablation (SRFA) in a large series of patients. Furthermore, to determine factors accounting for adverse outcomes. Material and methods: Between 2003 and 2018, 865 patients were treated by SRFA for 2653 primary and metastatic liver tumors with a median tumor size of 2.0 cm (0.5 - 19 cm). Primary technical efficacy (PTE) and local recurrence (LR) were evaluated, and possible predictors for adverse events analyzed using uni- and multi-variable binary logistic regression. Results: Overall, 2553 of 2653 tumors were successfully ablated at initial SRFA resulting in a PTE rate of 96.2%. Predictors of lower PTE rates were age > 70 years, tumor size > 5 cm, number of probes, location close to liver capsule/organs and segment II. LR occurred in 220 of 2653 tumors (8.3%) with the following predictors: age, tumor type/size, conglomerates, segments I/IVa/IVb, number of probes and location close to major vessels/bile duct. Multivariable analysis revealed tumor size > 5 cm (odds ratio [OR] 3.153), age > 70 years (OR 1.559), and location in segment II (OR 1.772) as independent prognostic factors for PTE, whereas tumor location close to major vessels (OR 1.653) and in segment IVb (OR 2.656) were identified as independent prognostic factors of LR. Conclusions: Stereotactic RFA is an attractive option in the management of primary or metastatic liver tumors with good local tumor control, even in large tumors. The presented prognostic factors for adverse local oncological outcome might help to stratify unfavorable tumors for ablation.
Image-guided percutaneous ablation techniques represent an attractive local therapy for the treatment of colorectal liver metastases (CLM) given its low risk of severe complications, which allows for early initiation of adjuvant therapies and spare functional liver parenchyma, allowing repeated treatments at the time of recurrence. However, ablation does not consistently achieve similar oncological outcomes to surgery, with the latter being currently considered the first-line local treatment modality in international guidelines. Recent application of computer-assisted ablation planning, guidance, and intra-procedural response assessment has improved percutaneous ablation outcomes. In addition, the evolving understanding of tumor molecular profiling has brought to light several biological factors associated with oncological outcomes following local therapies. The standardization of ablation procedures, the understanding of previously unknown biological factors affecting ablation outcomes, and the evidence by ongoing prospective clinical trials are poised to change the current perspective and indications on the use of ablation for CLM.
Objectives: This study aimed to assess the safety and efficacy of stereotactic radiofrequency ablation (SRFA) in patients with hepatocellular adenomas (HCA). Methods: Retrospective analyses of all patients referred for SRFA treatment at our institution between January 2010 and October 2020 revealed 14 patients (10 women; mean age 34.4 [range, 17-73 years]) with 38 HCAs treated through 18 ablation sessions. Ablations were considered successful if a safety margin >5 mm was achieved. Demographic, interventional, and outcome data were collected and analyzed. Primary and secondary technical efficacy rates were assessed based on follow-up images consisting of contrast-enhanced CT or MR scans. Results: The mean tumor size was 22 mm (range, 7-75 mm). Overall, 37/38 (97.4%) tumors were successfully ablated at the initial SRFA (primary efficacy rate of 97.4%). The median follow-up duration was 49.6 months. No deaths or adenoma-related complications (hemorrhage or malignant transformation) were observed. Disease-free survival rates at 1, 3, and 5 years from the date of the first SRFA were 100%, 85.8%, and 85.8%, respectively. Two patients developed new distant tumors retreated with consecutive re-ablation. No major complications occurred during any of the 18 ablation sessions. Conclusions: Percutaneous thermal ablation is efficient in the treatment of HCAs and may thus be considered a valid first-line treatment option. In addition, SRFA allows for an effective, minimally invasive treatment of large and multiple hepatic tumors within one session.
Alcohol-related liver disease (ALD) is a major cause of liver disease and represents a global burden, as treatment options are scarce. Whereas 90% of ethanol abusers develop alcoholic fatty liver disease (AFLD), only a minority evolves to steatohepatitis and cirrhosis. Alcohol increases lipogenesis and suppresses lipid-oxidation implying steatosis, although the key role of intestinal barrier integrity and microbiota in ALD has recently emerged. Bacteroides thetaiotaomicron (Bt) is a prominent member of human and murine intestinal microbiota, and plays important functions in metabolism, gut immunity, and mucosal barrier. We aimed to investigate the role of Bt in the genesis of ethanol-induced liver steatosis. Bt DNA was measured in feces of wild-type mice receiving a Lieber-DeCarli diet supplemented with an increase in alcohol concentration. In a second step, ethanol-fed mice were orally treated with living Bt, followed by analysis of intestinal homeostasis and histological and biochemical alterations in the liver. Alcohol feeding reduced Bt abundance, which was preserved by Bt oral supplementation. Bt-treated mice displayed lower hepatic steatosis and triglyceride content. Bt restored mucosal barrier and reduced LPS translocation by enhancing mucus thickness and production of Mucin2. Furthermore, Bt up-regulated Glucagon-like peptide-1 (GLP-1) expression and restored ethanol-induced Fibroblast growth factor 15 (FGF15) down-regulation. Lipid metabolism was consequently affected as Bt administration reduced fatty acid synthesis (FA) and improved FA oxidation and lipid exportation. Moreover, treatment with Bt preserved the mitochondrial fitness and redox state in alcohol-fed mice. In conclusion, recovery of ethanol-induced Bt depletion by oral supplementation was associated with restored intestinal homeostasis and ameliorated experimental ALD. Bt could serve as a novel probiotic to treat ALD in the future.
Background To increase safety in elite alpine ski racing Injury Surveillance Systems were implemented and preventive measures introduced. However, studies analysing the change in athletes’ injury risk by controlling for their exposure are still scarce. Objectives This study aimed to describe and analyse the risk of in-competition severe injury events (SIE comp ) in elite alpine ski racing. Methods Data recorded in the Austrian Ski Federation’s Injury Surveillance System were used to analyse the SIE comp incidence. Information on athletes’ competition exposure was obtained from the official website of the International Ski Federation. In 23 seasons, 2333 skier seasons were recorded for the Austrian Ski Team. Within a total of 114,531 runs 169 SIE comp occurred. Generalised Estimating Equation for Poisson Regressions were applied. Results The SIE comp incidence per 1000 runs was 1.48 [95% confidence interval (CI) 1.26–1.73] for elite alpine ski racers and 2.21 (95% CI 1.79–2.75) for the subgroup of World Cup racers. A significant sex difference was detected for the subgroup of junior racers with a higher risk for female athletes [risk ratio (RR): 2.97, 95% CI 1.46–6.05]. Between the seasons of 1997 and 2020, the seasonal SIE comp incidence increased by a factor of 2.67 for elite alpine ski racers and 3.53 for World Cup racers. Downhill (2.75, 95% CI 2.18–3.47) had the highest SIE comp incidence, followed by super-G (1.94, 95% CI 1.30–2.88), giant slalom (1.40, 95% CI 1.06–1.85), and slalom (0.64, 95% CI 0.43–0.96). Conclusion Although many preventive measures have been implemented in elite alpine ski racing, the risk of SIE comp has increased over the last two decades.
Background The use of extracorporeal membrane oxygenation (ECMO) in pediatric patients with underlying malignancies remains controversial. However, in an era in which the survival rates for children with malignancies have increased significantly and several recent reports have demonstrated effective ECMO use in children with cancer, we aimed to estimate the outcome and complications of ECMO treatment in these children. Methods We searched MEDLINE, Embase and CINAHL databases for studies on the use ECMO in pediatric patients with an underlying malignancy from inception to September 2020. This review was conducted in adherence to Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Study eligibility was independently assessed by two authors and disagreements resolved by a third author. Included studies were evaluated for quality using the Newcastle–Ottawa Scale (NOS). Random effects meta-analyses (DerSimonian and Laird) were performed. The primary outcomes were mortality during ECMO or hospital mortality. Results Thirteen retrospective, observational cohort studies were included, most of moderate quality (625 patients). The commonest indication for ECMO was severe respiratory failure (92%). Pooled mortality during ECMO was 55% (95% confidence interval [CI], 47–63%) and pooled hospital mortality was 60% (95% CI 54–67%). Although heterogeneity among the included studies was low, confidence intervals were large. In addition, the majority of the data were derived from registries with overlapping patients which were excluded for the meta-analyses to prevent resampling of the same participants across the included studies. Finally, there was a lack of consistent complications reporting among the studies. Conclusion Significantly higher mortalities than in general PICU patients was reported with the use of ECMO in children with malignancies. Although these results need to be interpreted with caution due to the lack of granular data, they suggest that ECMO appears to represents a viable rescue option for selected patients with underlying malignancies. There is an urgent need for additional data to define patients for whom ECMO may provide benefit or harm.
Emergency applications of rescue blankets go far beyond protection from hypothermia. In this review alternative applicabilities of these remarkable multifunctional tools were highlighted. Newly fabricated rescue blankets prove impressive robustness. The high tensile strength along with its low weight enable further applications, e.g. immobilization of injured extremities, splinting, wound dressing, a makeshift chest seal in sucking chest wounds, amongst others. Furthermore, the foil can be used as a vapour barrier, as eye protection and it can even be used to construct a stopgap bivouac sack, as alternative tool for transportation in the remote area and a wind shield or a water reservoir in the wilderness. During search-and-rescue missions the light reflection from the gold surface enhances visibility and increases the chance to be found. Rescue blankets are essential parts of first aid kits and backpacks in alpine and wilderness environment with multifunctional applicabilities. In this commentary to a review we want to evaluate the numerous applicabilities of rescue blankets in the treatment of emergencies by wilderness medicine and pre-hospital EMS.
Background We aimed to create a questionnaire to assess the health-related quality of life including functioning, symptoms, and general health status of adult patients with current or previous COVID-19. Here, we report on Phase I and II of the development. Methods Internationally recognized methodology for questionnaire development was followed. In Phase I, a comprehensive literature review was performed to identify relevant COVID-19 issues. Decisions for inclusion, exclusion, and data extraction were completed independently in teams of two and then compared. The resulting issues were discussed with health care professionals (HCPs) and current and former COVID-19 patients. The input of HCPs and patients was carefully considered, and the list of issues updated. In Phase II, this updated list was operationalized into items/questions. Results The literature review yielded 3342 publications, 339 of which were selected for full-text review, and 75 issues were identified. Discussions with 44 HCPs from seven countries and 52 patients from six countries showed that psychological symptoms, worries, and reduced functioning lasted the longest for patients, and there were considerable discrepancies between HCPs and patients concerning the importance of some of the symptoms. The final list included 73 issues, which were operationalized into an 80-item questionnaire. Conclusion The resulting COVID-19 questionnaire covers health–related quality of life issues relevant to COVID-19 patients and is available in several languages. The next steps include testing of the applicability and patients’ acceptability of the questionnaire (Phase IIIA) and preliminary psychometric testing (Phase IIIB).
Background Pain occurs in the majority of patients with late onset Pompe disease (LOPD) and is associated with a reduced quality of life. The aim of this study was to analyse the pain characteristics and its relation to a small nerve fiber involvement in LOPD patients. Methods In 35 patients with LOPD under enzyme replacement therapy without clinical signs of polyneuropathy (19 females; 51 ± 15 years), pain characteristics as well as depressive and anxiety symptoms were assessed using the PainDetect questionnaire (PDQ) and the hospital anxiety and depression scale (HADS), respectively. Distal skin biopsies were analysed for intraepidermal nerve fiber density (IENFD) and compared to age- and gender-matched reference data. Skin biopsies from 20 healthy subjects served as controls to assure validity of the morphometric analysis. Results Pain was reported in 69% of the patients with an average intensity of 4.1 ± 1.1 on the numeric rating scale (NRS; anchors: 0–10). According to PDQ, neuropathic pain was likely in one patient, possible in 29%, and unlikely in 67%. Relevant depression and anxiety symptoms occurred in 31% and 23%, respectively, and correlated with pain intensity. Distal IENFD (3.98 ± 1.95 fibers/mm) was reduced in 57% of the patients. The degree of IENFD reduction did not correlate with the durations of symptoms to ERT or duration of ERT to biopsy. Conclusions Pain is a frequent symptom in treated LOPD on ERT, though a screening questionnaire seldom indicated neuropathic pain. The high frequency of small nerve fiber pathology in a treated LOPD cohort was found regardless of the presence of pain or comorbid risk factors for SFN and needs further exploration in terms of clinical context, exact mechanisms and when developing novel therapeutic options for LOPD.
Myocardial injury often leads to heart failure due to the loss and insufficient regeneration of resident cardiomyocytes. The low regenerative potential of the mammalian heart is one of the main drivers of heart failure progression, especially after myocardial infarction accompanied by large contractile muscle loss. Preclinical therapies for cardiac regeneration are promising, but clinically still missing. Mammalian models represent an excellent translational in vivo platform to test drugs and treatments for the promotion of cardiac regeneration. Particularly, short-lived mice offer the possibility to monitor the outcome of such treatments throughout the life span. Importantly, there is a short period of time in newborn mice in which the heart retains full regenerative capacity after cardiac injury, which potentially also holds true for the neonatal human heart. Thus, in vivo neonatal mouse models of cardiac injury are crucial to gain insights into the molecular mechanisms underlying the cardiac regenerative processes and to devise novel therapeutic strategies for the treatment of diseased adult hearts. Here, we provide an overview of the established injury models to study cardiac regeneration. We summarize pioneering studies that demonstrate the potential of using neonatal cardiac injury models to identify factors that may stimulate heart regeneration by inducing endogenous cardiomyocyte proliferation in the adult heart. To conclude, we briefly summarize studies in large animal models and the insights gained in humans, which may pave the way toward the development of novel approaches in regenerative medicine.
Background The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Utility-Core 10 Dimensions (QLU-C10D) is a novel cancer-specific preference-based measure (PBM) for which value sets are being developed for an increasing number of countries. This is done by obtaining health preferences from the respective general population. There is an ongoing discussion if instead patients suffering from the disease in question should be asked for their preferences. We used the QLU-C10D valuation survey, originally designed for use in the general population, in a sample of cancer patients in Austria to assess the methodology’s acceptability and applicability in this target group before obtaining QLU-C10D patient preferences. Methods The core of the QLU-C10D valuation survey is a discrete choice experiment in which respondents are asked to give preferences for certain health states (described by a relatively large number of 10 quality of life domains) and an associated survival time. They therewith are asked to trade off quality of life against life time. As this might be a very burdensome task for cancer patients undergoing treatment, a cognitive interview was conducted in a pilot sample to assess burden and potential additional needs for explanation in order to be able to use the DCE for the development of QLU-C10D patient preferences. In addition, responses to general feedback questions on the survey were compared against responses from a matched control group from the already completed Austrian general population valuation survey. Results We included 48 patients (mean age 59.9 years; 46% female). In the cognitive interview, the majority indicated that their experience with the survey was positive (85%) and overall clarity as good (90%). In response to the general feedback questions, patients rated the presentation of the health states less clear than matched controls ( p = 0.008). There was no difference between patients and the general population concerning the difficulty in choosing between the health states ( p = 0.344). Conclusion Despite the relatively large number of DCE domains the survey was manageable for patients and allows going on with the QLU-C10D patient valuation study.
Purpose The aim of the study was to directly measure graft forces of an anterior cruciate ligament reconstruction (ACLR) and a lateral extra-articular tenodesis (LET) using the modified Lemaire technique in combined anterior cruciate ligament (ACL) deficient and anterolateral rotatory instable knees and to analyse the changes in knee joint motion resulting from combined ACLR + LET. Methods On a knee joint test bench, six fresh-frozen cadaveric specimens were tested at 0°, 30°, 60°, and 90° of knee flexion in the following states: 1) intact; 2) with resected ACL; 3) with resected ACL combined with anterolateral rotatory instability; 4) with an isolated ACLR; and 5) with combined ACLR + LET. The specimens were examined under various external loads: 1) unloaded; 2) with an anterior tibial translation force (ATF) of 98 N; 3) with an internal tibial torque (IT) of 5 Nm; and 4) with a combined internal tibial torque of 5 Nm and an anterior tibial translation force of 98 N (IT + ATF). The graft forces of the ACLR and LET were recorded by load cells incorporated into custom devices, which were screwed into the femoral tunnels. Motion of the knee joint was analysed using a 3D camera system. Results During IT and IT + ATF, the addition of a LET reduced the ACLR graft forces up to 61% between 0° and 60° of flexion ( P = 0.028). During IT + ATF, the LET graft forces reached 112 N. ACLR alone did not restore native internal tibial rotation after combined ACL deficiency and anterolateral rotatory instability. Combined ACLR + LET was able to restore native internal tibial rotation values for 0°, 60° and 90° of knee flexion with decreased internal tibial rotation at 30° of flexion. Conclusion The study demonstrates that the addition of a LET decreases the forces seen by the ACLR graft and reduces residual rotational laxity after isolated ACLR during internal tibial torque loading. Due to load sharing, a LET could support the ACLR graft and perhaps be the reason for reduced repeat rupture rates seen in clinical studies. Care must be taken not to limit the internal tibial rotation when performing a LET.
Purpose: Despite evidence for clinical benefits, recommendations in guidelines, and options for electronic data collection, routine assessment of patient-reported outcomes (PROs) is mostly not implemented in clinical practice. This study aimed to plan, conduct and evaluate the implementation of electronic PRO (e-PRO) assessment in the clinical routine of an inpatient radiation oncology clinic. Methods: The guideline- and evidence-based, stepwise approach of this single-center implementation study comprised preparatory analyses of current practice, selection of assessment instruments and times, development of staff training, and evidence-based recommendations regarding the use of the e-PRO assessment, as well as on-site support of the implementation. Process evaluation focused on potential clinical benefit (number of documented symptoms and supportive measures), feasibility and acceptance (patient contacts resulting in completion/non-completion of the e-PRO assessment, reasons for non-completion, preconditions, facilitators and barriers of implementation), and required resources (duration of patient contacts to explain/support the completion). Results: Selection of instruments and assessment times resulted in initial assessment at admission (EORTC QLQ-C30, QSR 10), daily symptom monitoring (EORTC single items), and assessment at discharge (EORTC QLQ-C30). Recommendations for PRO-based clinical action and self-management advice for patients concerning nine core symptoms were developed. Staff training comprised group and face-to-face meetings and an additional e-learning course was developed. Analyses of clinical records showed that e-PRO assessment identified more symptoms followed by a higher number of supportive measures compared to records of patients without e-PRO assessment. Analysis of n = 1597 patient contacts resulted in n = 1355 (84.9%) completed e-PROs (initial assessment: n = 355, monitoring: n = 967, final assessment: n = 44) and n = 242 (15.2%) non-completions. Instructions or support to complete e-PROs took on average 5.5 ± 5.3 min per patient contact. The most challenging issue was the integration of the results in clinical practice. Conclusion: E-PRO assessment in oncologic inpatient settings is acceptable for patients and can support symptom identification and the initiation of supportive measures. The challenge of making the "data actionable" within the clinical workflow and motivating clinical staff to use the results became evident.
Topological flow properties are proxies for mixing processes in aquifers and allow us to better understand the mechanisms controlling transport of solutes in the subsurface. However, topological descriptors, such as the Okubo–Weiss metric, are affected by the uncertainty in the solution of the flow problem. While the uncertainty related to the heterogeneous properties of the aquifer has been widely investigated in the past, less attention has been given to the one related to highly transient boundary conditions. We study the effect of different transient boundary conditions associated with hydropeaking events (i.e., artificial river stage fluctuations due to hydropower production) on groundwater flow and the Okubo–Weiss metric. We define deterministic and stochastic modeling scenarios applying four typical settings to describe river stage fluctuations during hydropeaking events: a triangular wave, a sine wave, a complex wave that results of the superposition of two sine waves, and a trapezoidal wave. We use polynomial chaos expansions to quantify the spatiotemporal uncertainty that propagates into the hydraulic head in the aquifer and the Okubo–Weiss. The wave-shaped highly transient boundary conditions influence not only the magnitude of the deformation and rotational forces of the flow field but also the temporal dynamics of dominance between local strain and rotation properties. Larger uncertainties are found in the scenario where the trapezoidal wave was imposed due to sharp fluctuation in the stage. The statistical moments that describe the propagation of the uncertainty highly vary depending on the applied boundary condition. Highlights Deterministic and stochastic scenarios to describe the groundwater flow field under river stage fluctuations during hydropeaking. Propagation of uncertainty of highly transient boundary conditions in the Okubo–Weiss metric. Highly transient boundary conditions can significantly affect mixing potential.
Background Noninvasive ventilation (NIV) is a promising alternative to invasive mechanical ventilation (IMV) with a particular importance amidst the shortage of intensive care unit (ICU) beds during the COVID-19 pandemic. We aimed to evaluate the use of NIV in Europe and factors associated with outcomes of patients treated with NIV. Methods This is a substudy of COVIP study—an international prospective observational study enrolling patients aged ≥ 70 years with confirmed COVID-19 treated in ICU. We enrolled patients in 156 ICUs across 15 European countries between March 2020 and April 2021.The primary endpoint was 30-day mortality. Results Cohort included 3074 patients, most of whom were male (2197/3074, 71.4%) at the mean age of 75.7 years (SD 4.6). NIV frequency was 25.7% and varied from 1.1 to 62.0% between participating countries. Primary NIV failure, defined as need for endotracheal intubation or death within 30 days since ICU admission, occurred in 470/629 (74.7%) of patients. Factors associated with increased NIV failure risk were higher Sequential Organ Failure Assessment (SOFA) score (OR 3.73, 95% CI 2.36–5.90) and Clinical Frailty Scale (CFS) on admission (OR 1.46, 95% CI 1.06–2.00). Patients initially treated with NIV (n = 630) lived for 1.36 fewer days (95% CI − 2.27 to − 0.46 days) compared to primary IMV group (n = 1876). Conclusions Frequency of NIV use varies across European countries. Higher severity of illness and more severe frailty were associated with a risk of NIV failure among critically ill older adults with COVID-19. Primary IMV was associated with better outcomes than primary NIV. Clinical Trial Registration NCT04321265 , registered 19 March 2020, https://clinicaltrials.gov .
Tensimetric studies on the reactivity of cationic oxo- (I[BArF24]) and thiophosphonium (II[BArF24]) Lewis acids towards the reference Lewis bases acetonitrile and pyridine are reported ([BArF24]⁻ = tetrakis[2,6-bis(trifluoromethyl)phenyl]borate). I[BArF24] forms a thermally stable 1:1 complex with pyridine and a solvate with acetonitrile, while II[BArF24] forms a labile complex with pyridine and a solvate with acetonitrile. The crystal structure of the acetonitrile solvate of I[BArF24] was determined by X-ray structural analysis. At elevated temperatures, reactions of perfluorinated anions with the glass of the apparatus were observed. Quantum chemical computations indicate that the Lewis acids undergo significant reorganization upon complex formation with pyridine. The stability of the cationic complexes with respect to dissociation decreases in the order I⁺·Py > II⁺·Py > I⁺·AN > II⁺·AN. Solvation in benzene and acetonitrile decreases dissociation energies of the complexes by 5 – 20 kJ mol⁻¹. Acetonitrile appears to be a suitable solvent for the reactivity studies of cationic oxo- and thiophosphonium Lewis acids.
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