[Basics for the Use of Andexanet]. / Grundlagen zur Anwendung von Andexanet.

BACKGROUND: For life-threatening or uncontrollable bleeding in association with the thrombin inhibitor dabigatran, the monoclonal antibody fragment idarucizumab is available, and for bleeding in association with the direct factor Xa inhibitors rivaroxaban or apixaban, the modified recombinant FXa protein andexanet is available for reversal. These antidotes represent emergency drugs that are typically used only after performing guideline-compliant multimodal measures. METHODS: An interdisciplinary group of experienced experts in the fields of angiology, hematology, internal medicine, clinical pharmacology, laboratory medicine, transfusion medicine, anesthesiology, intensive care, and hemostaseology developed recommendations relevant to daily clinical practice based on the current scientific evidence. RESULTS: Reversal of oral anticoagulants should be considered for severe bleeding in the following situations: (1) life-threatening bleeding or refractory hemorrhagic shock, (2) intracerebral bleeding, or (3) endoscopically unstoppable gastrointestinal bleeding. After successful hemostasis, anticoagulation (e.g., direct oral anticoagulant, vitamin K antagonist, and heparin) should be resumed promptly, taking into account individual bleeding and thromboembolic risk. DISCUSSION: This article aims to facilitate the management of patients with andexanet by all medical disciplines involved, thereby ensuring optimal care of patients during bleeding episodes.

Esophageal function and non-acid reflux evaluated by impedance-24 h-pH-metry, high-resolution manometry, and gastroscopy after one-anastomosis gastric bypass-outcomes of a prospective mid-term study.

BACKGROUND: One-Anastomosis Gastric Bypass (OAGB) is the third most common bariatric operation for patients with obesity worldwide. One concern about OAGB is the presence of acid and non-acid reflux in a mid- and long-term follow-up. The aim of this study was to objectively evaluate reflux and esophagus motility by comparing preoperative and postoperative mid-term outcomes. SETTING: Cross-sectional study; University-hospital based. METHODS: This study includes primary OAGB patients (preoperative gastroscopy, high-resolution manometry (HRM), and impedance-24 h-pH-metry) operated at Medical University of Vienna before 31st December 2017. After a mean follow-up of 5.1 ± 2.3 years, these examinations were repeated. In addition, history of weight, remission of associated medical problems (AMP), and quality of life (QOL) were evaluated. RESULTS: A total of 21 patients were included in this study and went through all examinations. Preoperative weight was 124.4 ± 17.3 kg with a BMI of 44.7 ± 5.6 kg/m2, total weight loss after 5.1 ± 2.3 years was 34.4 ± 8.3%. In addition, remission of AMP and QOL outcomes were very satisfactory in this study. In gastroscopy, anastomositis, esophagitis, Barrett´s esophagus, and bile in the pouch were found in: 38.1%, 28.3%, 9.5%, and 42.9%. Results of HRM of the lower esophageal sphincter pressure were 28.0 ± 15.6 mmHg, which are unchanged compared to preoperative values. Nevertheless, in the impedance-24 h-pH-metry, acid exposure time and DeMeester score decreased significantly to 1.2 ± 1.2% (p = 0.004) and 7.5 ± 8.9 (p = 0.017). Further, the total number of refluxes were equal to preoperative; however, the decreased acid refluxes were replaced by non-acid refluxes. CONCLUSION: This study has shown decreased rates of acid reflux and increased non-acid reflux after a mid-term outcome of primary OAGB patients. Gastroscopy showed signs of chronic irritation of the gastrojejunostomy, pouch, and distal esophagus, even in asymptomatic patients. Follow-up gastroscopies in OAGB patients after 5 years may be considered.

Outcome of Sleeve Gastrectomy Converted to Roux-en-Y Gastric Bypass and One-Anastomosis Gastric Bypass.

PURPOSE: Sleeve gastrectomy (SG) is the commonest bariatric procedure worldwide but there is also a high conversion rate mainly due to weight regain and gastroesophageal reflux disease (GERD) reported in studies with long-term follow-up. The aim of this study is to highlight benefits and limitations of converting SG patients to Roux-en-Y gastric bypass (RYGB) and one-anastomosis gastric bypass (OAGB). SETTING: Retrospective cross-sectional-study, medical university clinic setting. METHODS: This study includes all patients converted from primary SG to RYGB or OAGB by 12/2018 at the Medical University of Vienna. Patients were examined using gastroscopy, esophageal manometry, 24-h pH-metry, and questionnaires. RESULTS: Fifty-eight patients were converted from SG to RYGB (n = 45) or OAGB (n = 13). Total weight loss of patients converted to RYGB and OAGB was 41.5% and 44.8%, respectively, at nadir. Six patients had Barrett's esophagus (BE) after SG. In four out of these six patients, a complete remission of BE after conversion to RYGB was observed; nevertheless, two patients after RYGB and one after OABG newly developed BE. Clinical GERD improved at a higher rate after RYGB than after OAGB. Both revisional procedures improved associated medical problems. CONCLUSION: Conversion to RYGB is probably the best option for patients with GERD after SG. OAGB has shown a low potential to cure patients from GERD symptoms after SG. In terms of additional weight loss and remission of associated medical problems, both procedures studied were equal. Surveillance gastroscopies every 5 years after SG revisions are recommended.

[Oncologic aspects in treatment of pathologic fractures]. / Onkologische Aspekte der Behandlung pathologischer Frakturen.

BACKGROUND: Pathological fractures are not only incisive events for tumor patients often with the need of surgical treatment but also often represent a relevant challenge in the overall concept of oncological treatment. OBJECTIVE: The aim of this article is to illustrate the necessity of a pre-interventional interdisciplinary consideration of disease-specific and patient-specific characteristics. MATERIAL AND METHODS: A literature search and evaluation of existing guidelines were carried out including the keywords "bone metastases" and "pathological fractures" with respect to the oncological and radiotherapeutic treatment. RESULTS: An essential classification of the surgical and other needs for treatment is carried out by the identification of the underlying disease and dissemination situation. For tumor-related pathological fractures a palliative treatment situation is present in most cases. Nevertheless, a possible oligometastasis and an increasing number of effective systemic treatment methods must be taken into consideration when planning the surgical treatment. In addition to the therapeutic emergency indications in spinal compression or symptomatic hypercalcemia, both additive radiotherapy and supplementary pharmaceutical osteoprotection have to be addressed in this context. Radiotherapy in particular represents an effective alternative option for symptom and tumor control. CONCLUSION: The work-up of the multifaceted oncological treatment concept represents an interdisciplinary challenge, which ideally defines the further treatment procedure, including fracture treatment, in an interdisciplinary tumor board within an overall oncological concept.

[S2k Guideline - Recommendations for Inpatient Therapy of Patients with COVID-19]. / S2k-Leitlinie ­ Empfehlungen zur stationären Therapie von Patienten mit COVID-19.

Since December 2019, the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome - Corona Virus-2) has been spreading rapidly in the sense of a global pandemic. This poses significant challenges for clinicians and hospitals and is placing unprecedented strain on the healthcare systems of many countries. The majority of patients with Coronavirus Disease 2019 (COVID-19) present with only mild symptoms such as cough and fever. However, about 6 % require hospitalization. Early clarification of whether inpatient and, if necessary, intensive care treatment is medically appropriate and desired by the patient is of particular importance in the pandemic. Acute hypoxemic respiratory insufficiency with dyspnea and high respiratory rate (> 30/min) usually leads to admission to the intensive care unit. Often, bilateral pulmonary infiltrates/consolidations or even pulmonary emboli are already found on imaging. As the disease progresses, some of these patients develop acute respiratory distress syndrome (ARDS). Mortality reduction of available drug therapy in severe COVID-19 disease has only been demonstrated for dexamethasone in randomized controlled trials. The main goal of supportive therapy is to ensure adequate oxygenation. In this regard, invasive ventilation and repeated prone positioning are important elements in the treatment of severely hypoxemic COVID-19 patients. Strict adherence to basic hygiene, including hand hygiene, and the correct wearing of adequate personal protective equipment are essential when handling patients. Medically necessary actions on patients that could result in aerosol formation should be performed with extreme care and preparation.

Recommendations for treatment of critically ill patients with COVID-19 : Version 3 S1 guideline.

Since December 2019 a novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has rapidly spread around the world resulting in an acute respiratory illness pandemic. The immense challenges for clinicians and hospitals as well as the strain on many healthcare systems has been unprecedented.The majority of patients present with mild symptoms of coronavirus disease 2019 (COVID-19); however, 5-8% become critically ill and require intensive care treatment. Acute hypoxemic respiratory failure with severe dyspnea and an increased respiratory rate (>30/min) usually leads to intensive care unit (ICU) admission. At this point bilateral pulmonary infiltrates are typically seen. Patients often develop a severe acute respiratory distress syndrome (ARDS).So far, remdesivir and dexamethasone have shown clinical effectiveness in severe COVID-19 in hospitalized patients. The main goal of supportive treatment is to ascertain adequate oxygenation. Invasive mechanical ventilation and repeated prone positioning are key elements in treating severely hypoxemic COVID-19 patients.Strict adherence to basic infection control measures (including hand hygiene) and correct use of personal protection equipment (PPE) are essential in the care of patients. Procedures that lead to formation of aerosols should be carried out with utmost precaution and preparation.

Weight Loss and Resolution of Comorbidities After Sleeve Gastrectomy: A Review of Long-Term Results.

BACKGROUND AND AIMS:: Laparoscopic sleeve gastrectomy (SG) has massively increased in numbers over the last decade and is the most frequently performed bariatric procedure worldwide today. The aim of this review is to evaluate SG in terms of weight loss and resolution of comorbidities, based on data gained from the latest long-term studies available. MATERIAL AND METHODS:: This review includes the results of any long-term studies on SG available at this point as well as a selection of short- and mid-term studies. RESULTS:: There are only a handful of studies on sleeve gastrectomy with long-term follow-up available at this point. Conversion rates in these long-term studies amount to up to one-third of their cohorts; however, excess weight loss in patients maintaining their sleeve is over 50%. Results on the resolution of comorbidities vary among the studies available today. SUMMARY:: Sleeve gastrectomy is a valid bariatric method but one has to be aware of its limitations.

[Injury patterns in interstitial lung diseases]. / Schädigungsmuster interstitieller Lungenerkrankungen.

Interstitial lung diseases (ILD) consist of a complex group of hundreds of non-neoplastic pulmonary diseases with divergent clinical presentation, morphology and progression tendency. This great number of clinical entities contrasts with a limited number of injury patterns. By definition, an adequate classification requires a synopsis of the clinical, radiological and morphological findings. The ATS/ERS (American Thoracic Society/ European Respiratory Society) guidelines recommend an open lung biopsy if high-resolution computed tomography does not provide conclusive results. Due to the focal nature and overlapping features of injury patterns, microscopic categorization is not always possible. In order to broaden the diagnostic criteria by using molecular patterns the Lung Research Working Group of the Institute of Pathology of Hannover Medical School, Europe's leading transplant center, is working up fresh explanted human lungs in a standardized manner. These fresh specimens are used for translational research by means of functional, morphological and molecular techniques in order to identify disease-specific regulatory processes and to make them usable diagnostically and therapeutically.

Subcycle observation of lightwave-driven Dirac currents in a topological surface band.

Harnessing the carrier wave of light as an alternating-current bias may enable electronics at optical clock rates1. Lightwave-driven currents have been assumed to be essential for high-harmonic generation in solids2-6, charge transport in nanostructures7,8, attosecond-streaking experiments9-16 and atomic-resolution ultrafast microscopy17,18. However, in conventional semiconductors and dielectrics, the finite effective mass and ultrafast scattering of electrons limit their ballistic excursion and velocity. The Dirac-like, quasi-relativistic band structure of topological insulators19-29 may allow these constraints to be lifted and may thus open a new era of lightwave electronics. To understand the associated, complex motion of electrons, comprehensive experimental access to carrier-wave-driven currents is crucial. Here we report angle-resolved photoemission spectroscopy with subcycle time resolution that enables us to observe directly how the carrier wave of a terahertz light pulse accelerates Dirac fermions in the band structure of the topological surface state of Bi2Te3. While terahertz streaking of photoemitted electrons traces the electromagnetic field at the surface, the acceleration of Dirac states leads to a strong redistribution of electrons in momentum space. The inertia-free surface currents are protected by spin-momentum locking and reach peak densities as large as two amps per centimetre, with ballistic mean free paths of several hundreds of nanometres, opening up a realistic parameter space for all-coherent lightwave-driven electronic devices. Furthermore, our subcycle-resolution analysis of the band structure may greatly improve our understanding of electron dynamics and strong-field interaction in solids.

[Bridging anticoagulation in patients receiving vitamin K antagonists : Current status]. / Überbrückende Antikoagulation bei Patienten unter Vitamin-K-Antagonisten : Eine Bestandsaufnahme.

Approximately 30% of patients receiving oral anticoagulation using vitamin K antagonists (VKA) require surgery within 2 years. In this context, a clinical decision on the need and the mode of a peri-interventional bridging with heparin is needed. While a few years ago, bridging was almost considered a standard of care, recent study results triggered a discussion on which patients will need bridging at all. Revisiting the currently available recommendations and study results the conclusion can be drawn that the indications for bridging with heparin must nowadays be taken more narrowly and considering the individual patient risk of bleeding and thromboembolism. Bridging with heparin is only needed in patients with a very high risk of thromboembolism. This overview aims to give guidance for a risk-adapted peri-interventional approach to management of patients with a need for long-term anticoagulation using VKA.

[Bridging anticoagulation in patients receiving vitamin K antagonists : Current status]. / Überbrückende Antikoagulation bei Patienten unter Vitamin-K-Antagonisten : Eine Bestandsaufnahme.

Approximately 30% of patients receiving oral anticoagulation using vitamin K antagonists (VKA) require surgery within 2 years. In this context, a clinical decision on the need and the mode of a peri-interventional bridging with heparin is needed. While a few years ago, bridging was almost considered a standard of care, recent study results triggered a discussion on which patients will need bridging at all. Revisiting the currently available recommendations and study results the conclusion can be drawn that the indications for bridging with heparin must nowadays be taken more narrowly and considering the individual patient risk of bleeding and thromboembolism. Bridging with heparin is only needed in patients with a very high risk of thromboembolism. This overview aims to give guidance for a risk-adapted peri-interventional approach to management of patients with a need for long-term anticoagulation using VKA.

[Possibilities and limitations of molecular pathology in dermatohistology]. / Möglichkeiten und Grenzen der Molekularpathologie in der Dermatohistologie.

Malignant tumours, infections caused by microorganisms or genodermatoses are diagnosed with additional help of molecular pathology methods. Polymerase chain reaction (PCR), sequencing and in situ hybridisations play an important role. It remains to be seen if methods such as "liquid biopsies" or "single cell genomics" can be developed as routine diagnostics. High technical efforts, high costs and no possibility for resistency testing is accompanied by fast verification, high sensitivity and high specificity. Overall, molecular pathology results have to be combined with the clinical picture, histology or immunohistochemistry and culturing results to achieve a correct diagnosis for the patient.

Lightwave valleytronics in a monolayer of tungsten diselenide.

As conventional electronics approaches its limits 1 , nanoscience has urgently sought methods of fast control of electrons at the fundamental quantum level 2 . Lightwave electronics 3 -the foundation of attosecond science 4 -uses the oscillating carrier wave of intense light pulses to control the translational motion of the electron's charge faster than a single cycle of light5-15. Despite being particularly promising information carriers, the internal quantum attributes of spin 16 and valley pseudospin17-21 have not been switchable on the subcycle scale. Here we demonstrate lightwave-driven changes of the valley pseudospin and introduce distinct signatures in the optical readout. Photogenerated electron-hole pairs in a monolayer of tungsten diselenide are accelerated and collided by a strong lightwave. The emergence of high-odd-order sidebands and anomalous changes in their polarization direction directly attest to the ultrafast pseudospin dynamics. Quantitative computations combining density functional theory with a non-perturbative quantum many-body approach assign the polarization of the sidebands to a lightwave-induced change of the valley pseudospin and confirm that the process is coherent and adiabatic. Our work opens the door to systematic valleytronic logic at optical clock rates.

Higher prevalence of clinical cardiovascular comorbidities in postmenopausal women with self-reported premenopausal hirsutism and/or oligo-amenorrhea.

Hirsutism is a common condition, being present in about 5-15% of women. It is characterized by the growth of terminal hair in a pattern typical for men, like as hair growth in upper lip, chin, cheek and lower and upper abdomen. Not infrequently, hirsutism is followed by other signs of hyerandrogenism such as alopecia, acne, and seborrhea. The current study evaluated the association between a self-reported history of hirsutism and oligo-amenorrhea during reproductive age and the presence of several comorbidities in women after menopause. A total of 1057 women were investigated in a cross-sectional study, and information on the age at menarche, menstrual history, complaints about excessive hair growth, and disease development was obtained. Participants from the study were postmenopausal women aged >55 y who attended ac primary care service at least once during the 24-month period. Exclusion criteria included the presence of cognitive impairment and/or communication difficulties. Main outcomes were the presence of comorbidities after menopause. The prevalence of comorbidities was significantly higher in women with a history of hirsutism and/or oligo-amenorrhea [OR = 1.6 (95% CI 1.1-2.4), p = 0.002] or isolated hirsutism [OR 2.0 (95% CI 1.3-3.2), p = 0.004]. The prevalence of stroke, angina or myocardial infarction, cardiac failure, chronic obstructive pulmonary disease, and osteoarthritis were significantly higher in postmenopausal women who had experienced hirsutism and/or oligomenorrhea (p < 0.03). Limitations of the study came from the absence of a clear differentiation between hirsutism and hypertrichosis. According our results, the presence of hirsutism and oligo-amenorrhea during the female reproductive period may indicate susceptibility to important diseases at old age.

Symmetry-controlled time structure of high-harmonic carrier fields from a solid.

High-harmonic (HH) generation in crystalline solids1-6 marks an exciting development, with potential applications in high-efficiency attosecond sources7, all-optical bandstructure reconstruction8,9, and quasiparticle collisions10,11. Although the spectral1-4 and temporal shape5 of the HH intensity has been described microscopically1-6,12, the properties of the underlying HH carrier wave have remained elusive. Here we analyse the train of HH waveforms generated in a crystalline solid by consecutive half cycles of the same driving pulse. Extending the concept of frequency combs13-15 to optical clock rates, we show how the polarization and carrier-envelope phase (CEP) of HH pulses can be controlled by crystal symmetry. For some crystal directions, we can separate two orthogonally polarized HH combs mutually offset by the driving frequency to form a comb of even and odd harmonic orders. The corresponding CEP of successive pulses is constant or offset by π, depending on the polarization. In the context of a quantum description of solids, we identify novel capabilities for polarization- and phase-shaping of HH waveforms that cannot be accessed with gaseous sources.

Co-morbidities and bleeding in elderly patients with haemophilia-A survey of the German, Austrian and Swiss Society of Thrombosis and Haemostasis Research (GTH).

BACKGROUND: Nowadays patients with haemophilia survive longer due to improvements in haemophilia care. It has been hypothesized that the bleeding type and frequency may vary with age and are influenced by co-morbidities and co-medication in elderly patients. OBJECTIVES: To investigate a large group of patients older than 60 years of age with haemophilia concerning haemophilia treatment, bleeding pattern changes, co-morbidities, co-medication, bleeding sites and patient mortality. METHODS: A retrospective multi-centre data collection study was initiated on behalf of the German, Austrian and Swiss Society of Thrombosis and Haemostasis Research (GTH). Parameters of interest were investigated over the 5 years prior to study entry. RESULTS: A total of 185 haemophilia patients (mean age, 69.0±7.0 years, 29% with severe haemophilia) were included in the study. Regular prophylaxis was performed in 30% of the patients with severe haemophilia. In total, the annual bleeding rate was 2.49 and in patients with severe haemophilia 5.61, mostly caused by joint bleeds. Hypertension was the most common co-morbidity, but it occurred significantly less frequently than in an age-matched general population older than 70 years; 12% of the patients suffered from ischaemic heart disease, and 13% of the patients received anticoagulant or antiplatelet therapy. Within the observation period, 17% of the patients with severe haemophilia developed a higher frequency of bleeding symptoms, which was significantly associated with the use of antiplatelet or anticoagulant drugs. CONCLUSIONS: The most common co-morbidity of the patient population was hypertension, a considerable part had ischemic heart disease and antiplatelet or anticoagulant drugs.