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Abstract Understanding the impact of induction and maintenance therapy on patients’ quality of life (QoL) is important for treatment selection. This study aims to compare patient‐reported QoL between patients treated with KTd or KRd induction therapy and K maintenance therapy or observation. QoL was assessed using the EORTC QOL‐C 30 and QOL‐MY20 questionnaires in the AGMT‐02 study, in which 123 patients with newly diagnosed transplant ineligible multiple myeloma were randomized to nine cycles of either KTd or KRd induction therapy, followed by 12 cycles of K maintenance therapy, or observation. Longitudinal assessments showed statistically significant improvements in global health‐related QoL, various disease symptoms and pain for both treatment regimens. KTd improved insomnia and fatigue, and KRd improved physical functioning. Cross‐sectional comparisons indicated a “slight” superiority of KTd over KRd in several scales, with the exception of higher neuropathy scores with KTd. During maintenance, longitudinal comparisons showed no statistically significant changes. Cross‐sectional comparisons revealed a “slight” improvement in cognitive functioning during carfilzomib therapy, but a worsening in most other QoL scales. Induction therapy led to improvements in most QoL items, while maintenance therapy with K maintenance was associated with “slight” or “moderate” impairments in several QoL scales compared with the observation group.

Abstract Aims This study aims to investigate the prevalence of Takotsubo syndrome (TTS) as a percentage of the total number of acute coronary syndrome (ACS), including non‐STE‐elevation myocardial infarction and ST‐elevation myocardial infarction, as well as the short‐term outcome of TTS patients before and during the COVID‐19 pandemic. Methods and results We compared patients from two different periods: (i) Period 1 (before the COVID‐19 pandemic): 1 March to 30 December 2019, and (ii) Period 2 (during the COVID‐19 pandemic): 1 March to 30 December 2020. The retrospective database was created from the archives of the participating hospitals or electronic hospital systems by trained medical personnel. The subjects' medical history, cardiovascular risk factors, laboratory values, echocardiography findings, and an in‐hospital outcome were variables of interest. Furthermore, propensity score matching analysis was performed to evaluate the short‐term prognosis in TTS and ACS patients. Altogether six Austrian centres—(i) 3rd Medical Department of Cardiology and Intensive Care Medicine, Clinic Ottakring, Vienna, Austria; (ii) 5th Medical Department of Cardiology, Clinic Favoriten, Vienna, Austria; (iii) 2nd Medical Department, Hanusch Hospital, Vienna, Austria; (iv) University Clinic of Internal Medicine III, Cardiology and Angiology, Medical University of Innsbruck, Austria; (v) Department of Cardiology, University Hospital Graz, Graz, Austria; (vi) Department of Cardiology and Intensive Medicine, Kepler University Clinic, Linz, Austria—participated in the study. During period 1, 87 (3.5%) patients out of 2482 ACS patients had TTS in all participating centres. During period 2, 71 (2.7%) patients out of 2572 ACS patients had TTS in all participating centres. Accordingly, the prevalence of TTS remained stable irrespective of potential psychologic stress during the COVID pandemic. Furthermore, the baseline characteristics of TTS patients did not change during the COVID‐19 pandemic. The prevalence of in‐hospital complications [cardiogenic shock (4.6% vs. 4.3%, P = 0.925), ventricle thrombus (1.1% vs. 1.4%, P = 0.885) and in‐hospital bleeding (3.4% vs. 1.4%, P = 0.417)] remained stable. The all‐cause in‐hospital mortality of TTS patients did not change during the COVID‐19 pandemic [χ2(2) = 0.058, P = 0.810]. Moreover, a propensity score matching analysis of all‐cause in‐hospital mortality between matched TTS and ACS patients showed higher in‐hospital mortality in ACS patients during COVID‐19 pandemic (P = 0.043). Conclusions Despite the well‐known increased psychologic stress during the COVID‐19 pandemic, the prevalence of TTS during the COVID‐19 pandemic and the short‐term clinical outcome in Austria remained unimpacted.

Abstract Background The efficiency of pulmonary vein isolation (PVI) depends on the durability of RF lesions. Recent studies documented sustained continuity of ablation lines, improvements in durability, and expected clinical outcomes through altered settings in duration and power. However, the ablation strategy has not been adapted to this new approach and different biophysics of lesion formation. Purpose The aim of this study was to demonstrate that by adjusting the ablation approach to the broader geometry of lesions by increasing the minimal spacing between adjacent RF, a further significant reduction of procedural time while maintaining sufficient long‐term outcomes is achievable. Methods The presented study was a prospective, observational multi‐center trial. The periprocedural data were compared with data from a consecutively collected historical cohort. Results In total, 196 patients were included (mean age 62 ± 11 years, male 64.3%). Procedural duration, RF time, and LA dwelling time were significantly shorter in the HPSD group compared with the standard group (73 ± 26 min vs. 98 ± 36 min, p

Introduction Mechanical thrombectomy using stent retrievers and aspiration techniques has emerged as the standard of care for patients with acute ischemic stroke (AIS) secondary to emergent large vessel occlusion (LVO). This study intended to collect real‐world clinical evidence on the safety and effectiveness of endovascular treatment of AIS using the SOFIA Flow Plus 6F aspiration catheter. The primary endpoint was the proportion of subjects achieving mTICI ≥2b. Secondary endpoints included good functional outcomes (mRS 0‐2) at Day 90, revascularization time, first line and first pass mTICI ≥2b, occurrence of procedure‐related SAEs, vasospasm involving the accessed vascular tree, embolization to new territories (ENTs), symptomatic intracerebral hemorrhage (sICH) within 24 hours and mortality at Day 90. Methods SOFAST was a prospective, multicenter, single‐arm, observational post‐market study. The enrolled subjects were ≥21 and ≤85 years with large vessel (ICA or MCA) proximal occlusion, pre‐morbid mRS ≤1, baseline NIHSS ≥5, and for whom groin puncture was within 8 hours of symptom onset. A total of 108 patients were enrolled and treated using aspiration thrombectomy with SOFIA 6F as the first line treatment device. Patients were followed at 24 hours, 7 days/discharge, and 90 days post‐procedure. Cerebral angiography was performed pre‐ and post‐procedure. Clinical assessments included the NIHSS and mRS scales. All neurological, device‐related, and procedure‐related AEs and deaths were adjudicated by independent medical reviewers. Angiographic and other imaging data was adjudicated by an independent core laboratory. Results A total of 108 subjects were enrolled (mean age 62.7 years, 50% men) with a median NIHSS of 15.5. Of 108 subjects, 97.2% (105/108), 85.2% (92/108) and 55.6% (60/108) achieved mTICI ≥2b, ≥2c and =3 revascularization, respectively. With first line aspiration using SOFIA 6F, 87.0%, 79.6% and 52.8% achieved mTICI ≥2b, ≥2c and =3 revascularization, respectively. Median number of passes was one (range 1‐3). First pass rate of mTICI 2c or 3 using SOFIA 6F was 70.4%, of which 50.9% patients achieved mTICI score of 3. Mean duration from groin puncture to initial clot contact was 13.0 min and to successful revascularization was 17.9 min. Good functional outcome was achieved in 66.7% (72/108) of subjects at Day 90 (mRS 0‐2), procedure‐related SAEs occurred in 2.8% (3/108) of subjects and sICH in 0.9% (1/108) of subjects within 24 hours. Procedural vasospasm was recorded in in 9.3% (10/108) of subjects, and mortality in 7.4% (8/108) subjects at Day 90 (none related to the study device). No ENTs occurred. Conclusion In SOFAST study, mTICI ≥2b revascularization was achieved in the majority of patients at the end of all procedures (97.2%) and with first line treatment (87.0%) with a large fraction of these subjects achieving mTICI ≥2c following the first SOFIA 6F pass (70.4%). Durations from groin puncture to clot contact and successful revascularization were relatively short. The study presented high rates of good functional outcome at Day 90 and low rates of safety events. In summary, the study provides encouraging evidence of the safety and effectiveness of the SOFIA 6F device for aspiration thrombectomy in acute ischemic stroke subjects.

Abstract Four pinaceae pine resins analyzed in this study: black pine, shore pine, Baltic amber, and rosin demonstrate excellent dielectric properties, outstanding film forming, and ease of processability from ethyl alcohol solutions. Their trap‐free nature allows fabrication of virtually hysteresis‐free organic field effect transistors operating in a low voltage window with excellent stability under bias stress. Such green constituents represent an excellent choice of materials for applications targeting biocompatibility and biodegradability of electronics and sensors, within the overall effort of sustainable electronics development and environmental friendliness.

Abstract During skeletal development, bone growth and mineralization require transport of substantial amounts of calcium, while maintaining very low concentration. How an organism overcomes this major logistical challenge remains mostly unexplained. To shed some light on the dynamics of this process, cryogenic focused ion beam‐scanning electron microscopy (cryo‐FIB/SEM) is used to image forming bone tissue at day 13 of a chick embryo femur. Both cells and matrix in 3D are visualized and observed as calcium‐rich intracellular vesicular structures. Counting the number of these vesicles per unit volume and measuring their calcium content based on the electron back‐scattering signal, the intracellular velocity at which these vesicles need to travel to transport all the calcium required for the mineral deposited in one day within the collagenous tissue can be estimated. This velocity at 0.27 µm s−1 is estimated, which is too large for a diffusion process and rather suggests active transport through the cellular network. It is concluded that calcium logistics is hierarchical and based on several transport mechanisms: first through the vasculature using calcium‐binding proteins and the blood flow, then active transport over tens of micrometers through the network of osteoblasts and osteocytes, and finally diffusive transport over the last one or two microns.

Abstract Acute myocarditis following mRNA COVID‐19 vaccination was reported by the European Medicine Agency safety committee as a rare adverse event. We present a case series of three young male patients with suspected acute myocarditis following BNT162b2 mRNA COVID‐19 vaccination including results of endomyocardial biopsies (EMB). Additionally, we analysed EMB of another 21 patients with clinically suspected acute myocarditis following vaccination to determine the pathohistological pattern. Overall, EMB revealed acute lymphocytic myocarditis in 5 (20.8%), chronic lymphocytic myocarditis in 6 (25%), cardiac sarcoidosis in 1 (4.2%), healed myocarditis in 6 (25%), and other diagnoses with cardiac damage of unclear aetiology in 6 (25%) cases. Our findings support the necessity of EMB in patients with suspected acute myocarditis following mRNA COVID‐19 vaccination presenting with reduced EF to establish a correct and definite diagnosis. Concerns of these rare severe adverse events after COVID‐19 immunization should not undermine its value for the global community.

Abstract Background Gastrointestinal (GI) cancers were responsible for 26.3% of cancer cases and 35.4% of deaths worldwide in 2018. This study aimed to analyze the global incidence, mortality, prevalence, and contributing risk factors of the 6 major GI cancer entities [esophageal cancer (EC), gastric cancer (GC), liver cancer (LC), pancreatic cancer (PC), colon cancer, and rectal cancer]. Methods Using the Global Cancer Observatory and the Global Health Observatory databases, we reviewed the current GI cancer incidence, prevalence, and mortality, analyzed the association of GI cancer prevalence with national human development indices (HDIs), identified the contributing risk factors, and estimated developing age‐ and sex‐specific trends in incidence and mortality. Results In 2020, the trend in age‐standardized rate of incidence of GI cancers closely mirrored that of mortality, with the highest rates of LC, EC, and GC in Asia and of colorectal cancer (CRC) and PC mainly in Europe. Incidence and mortality were positively, but the mortality‐to‐incidence ratio (MIR) was inversely correlated with the national HDI levels. High MIRs in developing countries likely reflected the lack of preventive strategies and effective treatments. GI cancer prevalence was highest in Europe and was also positively correlated with HDIs and lifestyle‐associated risk factors, such as alcohol consumption, smoking, obesity, insufficient physical activity, and high blood cholesterol level, but negatively correlated with hypertension and diabetes. Incidences of EC were consistently and those of GC mostly decreasing, whereas incidences of CRC were increasing in most countries/regions, especially in the younger populations. Incidences of LC and PC were also increasing in all age‐gender populations except for younger males. Mortalities were decreasing for EC, GC, and CRC in most countries/regions, and age‐specific trends were observed in PC and LC with a decrease in the younger but an increase in the older population. Conclusions On the global scale, higher GI cancer burden was accompanied, for the most part, by factors associated with the so‐called Western lifestyle reflected by high and very high national HDI levels. In countries/regions with very high HDI levels, patients survived longer, and increasing GI cancer cases were observed with increasing national HDI levels. Optimizing GI cancer prevention and improving therapies, especially for patients with comorbid metabolic diseases, are thus urgently recommended.

Cardiac arrest still accounts for a substantial proportion of cardiovascular related deaths and is associated with a tremendous risk of neurological injury and, among the few survivors, poor quality of life. Critical determinants of survival and long‐term functional status after cardiac arrest are timely initiation of cardiopulmonary resuscitation and use of an external defibrillator for patients with a shockable rhythm. Outcomes are still far from satisfactory, despite ongoing efforts to improve cardiac arrest response systems, as well as elaborate postresuscitation algorithms. Targeted temperature management at the wide range between 32 °C and 36 °C has been one of the main therapeutic strategies to improve neurological outcome in postresuscitation care. This recommendation has been mainly based on 2 small randomized trials that were published 20 years ago. Most recent data derived from the TTM2 (Targeted Hypothermia Versus Targeted Normothermia After Out‐of‐Hospital Cardiac Arrest) trial, which included 1861 patients, challenge this strategy. It showed no benefit of targeted hypothermia at 33 °C over normothermia at 36 °C to 37.5 °C with fever prevention. Because temperature management at lower temperatures also correlated with an increased risk of side effects without any benefit in the TTM2 trial, a modification of the guidelines with harmonizing temperature management to normothermia might be necessary.

Abstract Objective Reduction in glucocerebrosidase (GCase; encoded by GBA) enzymatic activity has been linked to Parkinson’s disease (PD). Here, we correlated GCase activity and PD phenotype in the Parkinson’s Progression Markers Initiative (PPMI) cohort. Methods We measured GCase activity in dried blood spots from 1559 samples of participants in the inception PPMI cohort, collected in four annual visits (from baseline visit to Year‐3). Participants (PD, n = 392; controls, n = 175) were fully sequenced for GBA variants by means of genome‐wide genotyping arrays, whole‐exome sequencing, whole‐genome sequencing, Sanger sequencing, and RNA‐sequencing. Results Fifty‐two PD participants (13.4%) and 13 (7.4%) controls carried a GBA variant. GBA status was strongly associated with GCase activity. Among noncarriers, GCase activity was similar between PD and controls. Among GBA p.E326K carriers (PD, n = 20; controls, n = 5), activity was significantly lower in PD carriers than control carriers (9.53 µmol/L/h vs. 11.68 µmol/L/h, P = 0.035). Glucocerebrosidase activity was moderately (r = 0.45) associated with white blood cell (WBC) count. Next, we divided the noncarriers with PD to tertiles based on WBC count‐corrected enzymatic activity. Members of the lower tertile had higher MDS‐Unified Parkinson’s Disease Rating Scale motor score in the “off” medication examination at year‐III exam. Longitudinal analyses demonstrated slight reduction of activity in samples collected earlier on in the study, likely because of longer storage time. Interpretation GCase activity is associated with GBA genotype, WBC count, and among p.E326K variant carriers, with PD status. Reduced activity may also be associated with worse phenotype but longer follow up is required to confirm this observation.

Abstract Aims Treating patients with acute decompensated heart failure (ADHF) presenting with volume overload is a common task. However, optimal guidance of decongesting therapy and treatment targets are not well defined. The inferior vena cava (IVC) diameter and its collapsibility can be used to estimate right atrial pressure, which is a measure of right‐sided haemodynamic congestion. The CAVA‐ADHF‐DZHK10 trial is designed to test the hypothesis that ultrasound assessment of the IVC in addition to clinical assessment improves decongestion as compared with clinical assessment alone. Methods and results CAVA‐ADHF‐DZHK10 is a randomized, controlled, patient‐blinded, multicentre, parallel‐group trial randomly assigning 388 patients with ADHF to either decongesting therapy guided by ultrasound assessment of the IVC in addition to clinical assessment or clinical assessment alone. IVC ultrasound will be performed daily between baseline and hospital discharge in all patients. However, ultrasound results will only be reported to treating physicians in the intervention group. Treatment target is relief of congestion‐related signs and symptoms in both groups with the additional goal to reduce the IVC diameter ≤21 mm and increase IVC collapsibility >50% in the intervention group. The primary endpoint is change in N‐terminal pro‐brain natriuretic peptide from baseline to hospital discharge. Secondary endpoints evaluate feasibility, efficacy of decongestion on other scales, and the impact of the intervention on clinical endpoints. Conclusions CAVA‐ADHF‐DZHK10 will investigate whether IVC ultrasound supplementing clinical assessment improves decongestion in patients admitted for ADHF.

Abstract Infection with SARS‐CoV‐2 is associated with thromboinflammation, involving thrombotic and inflammatory responses, in many COVID‐19 patients. In addition, immune dysfunction occurs in patients characterised by T cell exhaustion and severe lymphopenia. We investigated the distribution of phosphatidylserine (PS), a marker of dying cells, activated platelets and platelet‐derived microparticles (PMP), during the clinical course of COVID‐19. We found an unexpectedly high amount of blood cells loaded with PS+ PMPs for weeks after the initial COVID‐19 diagnosis. Elevated frequencies of PS+PMP+ PBMCs correlated strongly with increasing disease severity. As a marker, PS outperformed established laboratory markers for inflammation, leucocyte composition and coagulation, currently used for COVID‐19 clinical scoring. PS+ PMPs preferentially bound to CD8+ T cells with gene expression signatures of proliferating effector rather than memory T cells. As PS+ PMPs carried programmed death‐ligand 1 (PD‐L1), they may affect T cell expansion or function. Our data provide a novel marker for disease severity and show that PS, which can trigger the blood coagulation cascade, the complement system, and inflammation, resides on activated immune cells. Therefore, PS may serve as a beacon to attract thromboinflammatory processes towards lymphocytes and cause immune dysfunction in COVID‐19.

The clinical and immunological impact of B-cell depletion in the context of coronavirus disease 2019 (COVID-19) is unclear. We conducted a prospectively planned analysis of COVID-19 in patients who received B-cell depleting anti-CD20 antibodies and chemotherapy for B-cell lymphomas. The control cohort consisted of age- and sex-matched patients without lymphoma who were hospitalized because of COVID-19. We performed detailed clinical analyses, in-depth cellular and molecular immune profiling, and comprehensive virological studies in 12 patients with available biospecimens. B-cell depleted lymphoma patients had more severe and protracted clinical course (median hospitalization 88 versus 17 d). All patients actively receiving immunochemotherapy (n = 5) required ICU support including long-term mechanical ventilation. Neutrophil recovery following granulocyte colony stimulating factor stimulation coincided with hyperinflammation and clinical deterioration in 4 of the 5 patients. Immune cell profiling and gene expression analysis of peripheral blood mononuclear cells revealed early activation of monocytes/macrophages, neutrophils, and the complement system in B-cell depleted lymphoma patients, with subsequent exacerbation of the inflammatory response and dysfunctional interferon signaling at the time of clinical deterioration of COVID-19. Longitudinal immune cell profiling and functional in vitro assays showed SARS-CoV-2-specific CD8+ and CD4+ T-effector cell responses. Finally, we observed long-term detection of SARS-CoV-2 in respiratory specimens (median 84 versus 12 d) and an inability to mount lasting SARS-CoV-2 antibody responses in B-cell depleted lymphoma patients. In summary, we identified clinically relevant particularities of COVID-19 in lymphoma patients receiving B-cell depleting immunochemotherapies.

Abstract Global warming is leading to increased heat stress in many regions around the world. An extensive number of heat stress indicators (HSIs) has been developed to measure the associated impacts on human health. Here we calculate eight HSIs for global climate models participating in the Coupled Model Intercomparison Project Phase 6 (CMIP6). We compare their future trends as function of global mean temperature, with particular focus on highly populated regions. All analyzed HSIs increase significantly (p

Background: There exists a dearth of evidence on rehabilitation factors that influence prosthetic mobility in people with lower limb amputation (LLA). Examining variables that contribute to prosthetic mobility can inform rehabilitation interventions, providing guidance in developing more comprehensive care for these individuals., Objective: To determine the influence of modifiable and non-modifiable variables related to LLA and their impact on prosthetic mobility, using the International Classification of Functioning, Disability and Health (ICF) model. Secondarily, to determine if personal factors and self-reported balance and mobility are predictive of Component timed-up-and-go (cTUG) performance., Design: Cross-sectional study of a convenience sample., Setting: National conference., Participants: People (N=68) with non-vascular causes of unilateral LLA., Methods: Assessment of anthropometrics, mobility, bilateral hip extensor strength, hip range of motion, single limb balance, and self report measures. Lasso linear regression and extreme gradient boosting analyses were used to determine influence of variables on prosthetic mobility., Main Outcome Measure: Timed performance of the cTUG., Results: The following five variables were found to influence basic prosthetic mobility (P ≤ .05) in people with transtibial amputation: hip extensor strength, hip range of motion, single limb balance, waist circumference, and age. In the transfemoral cohort, number of comorbidities and waist circumference primarily influenced prosthetic mobility. Additionally, 66% of the variance in cTUG total time for the entire sample could be explained by simply regressing on level of amputation, number of comorbidities, age and Activities-specific Balance Confidence scale score, all variables easily collected in a waiting room., Conclusion: Variables that are modifiable with physical therapy intervention including hip extensor strength, hip range of motion, single limb balance, and waist circumference significantly influenced basic prosthetic mobility. These variables can be affected by targeted rehabilitation interventions and lifestyle changes., Level of Evidence: II., (© 2019 American Academy of Physical Medicine and Rehabilitation.)

This paper reports the results of a best-worst scaling (BWS) study to value the Investigating Choice Experiments Capability Measure for Adults (ICECAP-A), a new capability measure among adults, in a UK setting. A main effects plan plus its foldover was used to estimate weights for each of the four levels of all five attributes. The BWS study was administered to 413 randomly sampled individuals, together with sociodemographic and other questions. Scale-adjusted latent class analyses identified two preference and two (variance) scale classes. Ability to characterize preference and scale heterogeneity was limited, but data quality was good, and the final model exhibited a high pseudo-r-squared. After adjusting for heterogeneity, a population tariff was estimated. This showed that 'attachment' and 'stability' each account for around 22% of the space, and 'autonomy', 'achievement' and 'enjoyment' account for around 18% each. Across all attributes, greater value was placed on the difference between the lowest levels of capability than between the highest. This tariff will enable ICECAP-A to be used in economic evaluation both within the field of health and across public policy generally., (© 2013 The Authors. Health Economics published by John Wiley & Sons Ltd.)

Total phenolic choline ester fractions prepared from seeds of Arabidopsis thaliana and Brassica napus were analyzed by capillary LC/ESI-QTOF-MS and direct infusion ESI-FTICR-MS. In addition to the dominating sinapoylcholine, 30 phenolic choline esters could be identified based on accurate mass measurements, interpretation of collision-induced dissociation (CID) mass spectra, and synthesis of selected representatives. The compounds identified so far include substituted hydroxycinnamoyl- and hydroxybenzoylcholines, respective monohexosides as well as oxidative coupling products of phenolic choline esters and monolignols. Phenolic choline esters are well separable by reversed-phase liquid chromatography and sensitively detectable using electrospray ionization mass spectrometry in positive ion mode. CID mass spectra obtained from molecular ions facilitate the characterization of both the type and substitution pattern of such compounds. Therefore, LC/ESI-MS/MS represents a valuable tool for comprehensive qualitative and quantitative analysis of this compound class., (Copyright (c) 2009 John Wiley & Sons, Ltd.)