Remote Design of a Smartphone and Wearable Detected Atrial Arrhythmia in Older Adults Case Finding Study: Smart in OAC - AFNET 9.

Introduction: Screening for atrial fibrillation and timely initiation of oral anticoagulation, rhythm management, and treatment of concomitant cardiovascular conditions can improve outcomes in high-risk populations. Whether wearables can facilitate screening in older adults is not known. Methods and Analyses: The multicenter, international, investigator-initiated, single-arm case-finding Smartphone and wearable detected atrial arrhythmia in older adults case finding study (Smart in OAC - AFNET 9) evaluates the diagnostic yield of a validated, cloud-based analysis algorithm detecting atrial arrhythmias via a signal acquired by a smartphone-coupled wristband monitoring system in older adults. Unselected participants aged ≥65 years without known atrial fibrillation and not receiving oral anticoagulation are enrolled in three European countries. Participants undergo continuous pulse monitoring using a wristband with a photo plethysmography (PPG) sensor and a telecare analytic service. Participants with PPG-detected atrial arrhythmias will be offered ECG loop monitoring. The study has a virtual design with digital consent and teleconsultations, whilst including hybrid solutions. Primary outcome is the proportion of older adults with newly detected atrial arrhythmias (NCT04579159). Discussion: Smart in OAC - AFNET 9 will provide information on wearable-based screening for PPG-detected atrial arrhythmias in Europe and provide an estimate of the prevalence of atrial arrhythmias in an unselected population of older adults.

Smartphone and wearable detected atrial arrhythmias in Older Adults: Results of a fully digital European Case finding study.

Aims: Simplified detection of atrial arrhythmias via consumer-electronics would enable earlier therapy in at-risk populations. Whether this is feasible and effective in older populations is not known. Methods and results: The fully remote, investigator-initiated Smartphone and wearable detected atrial arrhythmia in Older Adults Case finding study (Smart in OAC-AFNET 9) digitally enrolled participants ≥65 years without known atrial fibrillation, not receiving oral anticoagulation in Germany, Poland, and Spain for 8 weeks. Participants were invited by media communications and direct contacts. Study procedures adhered to European data protection. Consenting participants received a wristband with a photoplethysmography sensor to be coupled to their smartphone. The primary outcome was the detection of atrial arrhythmias lasting 6 min or longer in the first 4 weeks of monitoring. Eight hundred and eighty-two older persons (age 71 ± 5 years, range 65-90, 500 (57%) women, 414 (47%) hypertension, and 97 (11%) diabetes) recorded signals. Most participants (72%) responded to adverts or word of mouth, leaflets (11%) or general practitioners (9%). Participation was completely remote in 469/882 persons (53%). During the first 4 weeks, participants transmitted PPG signals for 533/696 h (77% of the maximum possible time). Atrial arrhythmias were detected in 44 participants (5%) within 28 days, and in 53 (6%) within 8 weeks. Detection was highest in the first monitoring week [incidence rates: 1st week: 3.4% (95% confidence interval 2.4-4.9); 2nd-4th week: 0.55% (0.33-0.93)]. Conclusion: Remote, digitally supported consumer-electronics-based screening is feasible in older European adults and identifies atrial arrhythmias in 5% of participants within 4 weeks of monitoring (NCT04579159).

Therapy-related myelodysplastic syndromes deserve specific diagnostic sub-classification and risk-stratification-an approach to classification of patients with t-MDS.

In the current World Health Organization (WHO)-classification, therapy-related myelodysplastic syndromes (t-MDS) are categorized together with therapy-related acute myeloid leukemia (AML) and t-myelodysplastic/myeloproliferative neoplasms into one subgroup independent of morphologic or prognostic features. Analyzing data of 2087 t-MDS patients from different international MDS groups to evaluate classification and prognostication tools we found that applying the WHO classification for p-MDS successfully predicts time to transformation and survival (both p < 0.001). The results regarding carefully reviewed cytogenetic data, classifications, and prognostic scores confirmed that t-MDS are similarly heterogeneous as p-MDS and therefore deserve the same careful differentiation regarding risk. As reference, these results were compared with 4593 primary MDS (p-MDS) patients represented in the International Working Group for Prognosis in MDS database (IWG-PM). Although a less favorable clinical outcome occurred in each t-MDS subset compared with p-MDS subgroups, FAB and WHO-classification, IPSS-R, and WPSS-R separated t-MDS patients into differing risk groups effectively, indicating that all established risk factors for p-MDS maintained relevance in t-MDS, with cytogenetic features having enhanced predictive power. These data strongly argue to classify t-MDS as a separate entity distinct from other WHO-classified t-myeloid neoplasms, which would enhance treatment decisions and facilitate the inclusion of t-MDS patients into clinical studies.

Randomized phase-II trial evaluating induction therapy with idarubicin and etoposide plus sequential or concurrent azacitidine and maintenance therapy with azacitidine.

The aim of this randomized phase-II study was to evaluate the effect of substituting cytarabine by azacitidine in intensive induction therapy of patients with acute myeloid leukemia (AML). Patients were randomized to four induction schedules for two cycles: STANDARD (idarubicin, cytarabine, etoposide); and azacitidine given prior (PRIOR), concurrently (CONCURRENT), or after (AFTER) therapy with idarubicin and etoposide. Consolidation therapy consisted of allogeneic hematopoietic-cell transplantation or three courses of high-dose cytarabine followed by 2-year maintenance therapy with azacitidine in the azacitidine-arms. AML with CBFB-MYH11, RUNX1-RUNX1T1, mutated NPM1, and FLT3-ITD were excluded and accrued to genotype-specific trials. The primary end point was response to induction therapy. The statistical design was based on an optimal two-stage design applied for each arm separately. During the first stage, 104 patients (median age 62.6, range 18-82 years) were randomized; the study arms PRIOR and CONCURRENT were terminated early due to inefficacy. After randomization of 268 patients, all azacitidine-containing arms showed inferior response rates compared to STANDARD. Event-free and overall survival were significantly inferior in the azacitidine-containing arms compared to the standard arm (p < 0.001 and p = 0.03, respectively). The data from this trial do not support the substitution of cytarabine by azacitidine in intensive induction therapy.

The IPSS-R has prognostic impact in untreated patients with MDS del(5q).

The IPSS-R proved to be a powerful tool for the assessment of prognosis in MDS patients. We aimed at a validation of the IPSS-R for patients with MDS harboring deletion (5q) isolated or accompanied by additional aberrations. The study was based on 444 MDS patients from MDS centers in Europe. 67% of the patients were female, median age was 69 years. 43.5% had MDS del(5q), 5.9% were diagnosed with RCUD, 2.0% RARS, 18.4% RCMD, 14.6% RAEB-I and 15.5% RAEB-II. According to the IPSS-R, there were 9.9% very low, 39.6% low, 16.6% intermediate, 12.8% high, 20.9% very high risk patients. For very low risk patients survival was 7.5 years, low 9.0 years, intermediate 6.5 years, high 1.5 years and very high 0.7 years (p < 0.001). For low and intermediate risk, the probability of AML evolution was significantly different (p = 0.03) as well as for high versus very high risk groups (p = 0.002). The IPSS-R proved to be an appropriate prognostic tool for MDS with del(5q).

[Robot-assisted surgery - Progress or expensive toy? : Matched-pair comparative analysis of robot-assisted cholecystectomy vs. laparoscopic cholecystectomy]. / Roboterassistierte Chirurgie ­ Fortschritt oder teures Spielzeug? : Matched-Pair-Vergleichsanalyse der roboterassistierten Cholezystektomie vs. der laparoskopischen Cholezystektomie.

AIM AND METHODS: By means of a matched-pair analysis comparing data obtained from laparoscopic cholecystectomy (LC) and robot-assisted laparoscopic cholecystectomy (RAC), the value of both methods as well as the advantages and disadvantages of both approaches were elucidated. The consideration was carried out by evaluation of postoperative surgical results, a cost analysis and a subjective survey of the patients using a questionnaire. Thus, from the 35 consecutive RAC, 35 (parallel) retrospectively matched pairs were established. RESULTS: Postoperative surgical results did not show any significant differences between LC and RAC. In the individual assessment by each patient, there were also no significant differences; however, there was a tendency towards the assessment of the RAC to be slightly worse. A striking difference was found with respect to the cost analysis at the time of surgery. CONCLUSION: The RAC operation alone is significantly more expensive compared to LC with respect to maintenance and acquisition costs. In addition, RAC can at present not be completely reimbursed under the current German diagnosis-related system. The postulated advantages of RAC comprise mainly the precise preparation within narrow confinements and the favorable ergonomic handling for the surgeon. The basic prerequisites are control of the costs and a reasonable reflection in the current reimbursement system.

Effect of side-chain asymmetry on the intermolecular structure and order-disorder transition in alkyl-substituted polyfluorenes.

We study relations among the side-chain asymmetry, structure, and order-disorder transition (ODT) in hairy-rod-type poly(9,9-dihexylfluorene) (PF6) with two identical side chains and atactic poly(9-octyl-9-methyl-fluorene) (PF1-8) with two different side chains per repeat. PF6 and PF1-8 organize into alternating side-chain and backbone layers that transform into an isotropic phase at T^{ODT}(PF6) and T_{bi}^{ODT}(PF1-8). We interpret polymers in terms of monodisperse and bidisperse brushes and predict scenarios T^{ODT}

A new potassium-based intermediate and its role in the desorption properties of the K-Mg-N-H system.

New insights into the reaction pathways of different potassium/magnesium amide-hydride based systems are discussed. In situ SR-PXD experiments were for the first time performed in order to reveal the evolution of the phases connected with the hydrogen releasing processes. Evidence of a new K-N-H intermediate is shown and discussed with particular focus on structural modification. Based on these results, a new reaction mechanism of amide-hydride anionic exchange is proposed.

Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM).

A risk-adapted treatment strategy is mandatory for myelodysplastic syndromes (MDS). We refined the World Health Organization (WHO)-classification-based Prognostic Scoring System (WPSS) by determining the impact of the newer clinical and cytogenetic features, and we compared its prognostic power to that of the revised International Prognostic Scoring System (IPSS-R). A population of 5326 untreated MDS was considered. We analyzed single WPSS parameters and confirmed that the WHO classification and severe anemia provide important prognostic information in MDS. A strong correlation was found between the WPSS including the new cytogenetic risk stratification and WPSS adopting original criteria. We then compared WPSS with the IPSS-R prognostic system. A highly significant correlation was found between the WPSS and IPSS-R risk classifications. Discrepancies did occur among lower-risk patients in whom the number of dysplastic hematopoietic lineages as assessed by morphology did not reflect the severity of peripheral blood cytopenias and/or increased marrow blast count. Moreover, severe anemia has higher prognostic weight in the WPSS versus IPSS-R model. Overall, both systems well represent the prognostic risk of MDS patients defined by WHO morphologic criteria. This study provides relevant in formation for the implementation of risk-adapted strategies in MDS.

Automated approximation of center of mass position in X-ray sequences of animal locomotion.

A crucial aspect of comparative biomechanical research is the center of mass (CoM) estimation in animal locomotion scenarios. Important applications include the parameter estimation of locomotion models, the discrimination of gaits, or the calculation of mechanical work during locomotion. Several methods exist to approximate the CoM position, e.g. force-plate-based approaches, kinematic approaches, or the reaction board method. However, they all share the drawback of not being suitable for large scale studies, as detailed initial conditions from kinematics are required (force-plates), manual interaction is necessary (kinematic approach), or only static settings can be analyzed (reaction board). For the increasingly popular case of X-ray-based animal locomotion analysis, we present an alternative approach for CoM estimation which overcomes these shortcomings. The main idea is to only use the recorded X-ray images, and to map each pixel to the mass of matter it represents. As a consequence, our approach is surgically noninvasive, independent of animal species and locomotion characteristics, and neither requires prior knowledge nor any kind of user interaction. To assess the quality of our approach, we conducted a comparison to highly accurate reaction board experiments for lapwing and rat cadavers, and achieved an average accuracy of 2.6mm (less than 2% of the animal body length). We additionally verified the practical applicability of the algorithm by comparison to a previously published CoM study which is based on the kinematic method, yielding comparable results.

Monosomal karyotype in MDS: explaining the poor prognosis?

Monosomal karyotype (MK) is associated with an adverse prognosis in patients in acute myeloid leukemia (AML). This study analyzes the prognostic impact of MK in a cohort of primary, untreated patients with myelodysplastic syndromes (MDS). A total of 431 patients were extracted from an international database. To analyze whether MK is an independent prognostic marker in MDS, cytogenetic and clinical data were explored in uni- and multivariate models regarding overall survival (OS) as well as AML-free survival. In all, 204/431 (47.3%) patients with MK were identified. Regarding OS, MK was prognostically significant in patients with ≤ 4 abnormalities only. In highly complex karyotypes (≥ 5 abnormalities), MK did not separate prognostic subgroups (median OS 4.9 months in MK+ vs 5.6 months in patients without MK, P=0.832). Based on the number of abnormalities, MK-positive karyotypes (MK+) split into different prognostic subgroups (MK+ and 2 abnormalities: OS 13.4 months, MK+ and 3 abnormalities: 8.0 months, MK+ and 4 abnormalities: 7.9 months and MK+ and ≥ 5 abnormalities: 4.9 months; P<0.01). In multivariate analyses, MK was not an independent prognostic factor. Our data support the hypothesis that a high number of complex abnormalities, associated with an instable clone, define the subgroup with the worst prognosis in MDS, independent of MK.

Structural study of helical polyfluorene under high quasihydrostatic pressure.

We report on an x-ray diffraction (XRD) study of helical poly[9,9-bis(2-ethylhexyl)fluorene] (PF2/6) under high quasihydrostatic pressure and show an effect of pressure on the torsion angle (dihedral angle) between adjunct repeat units and on the hexagonal unit cell. A model for helical backbone conformation is constructed. The theoretical position for the most prominent 00l x-ray reflection is calculated as a function of torsion angle. The XRD of high molecular weight PF2/6 (M(n)=30 kg/mol) is measured through a diamond anvil cell upon pressure increase from 1 to 10 GPa. The theoretically considered 00l reflection is experimentally identified, and its shift with the increasing pressure is found to be consistent with the decreasing torsion angle between 2 and 6 GPa. This indicates partial backbone planarization towards a more open helical structure. The h00 peak is identified, and its shift together with the broadening of 00l implies impairment of the ambient hexagonal order, which begins at or below 2 GPa. Previously collected high-pressure photoluminescence data are reanalyzed and are found to be qualitatively consistent with the XRD data. This paper provides an example of how the helical π-conjugated backbone structure can be controlled by applying high quasihydrostatic pressure without modifications in its chemical structure. Moreover, it paves the way for wider use of high-pressure x-ray scattering in the research of π-conjugated polymers.