[Interdisciplinary neurovascular networks: state of the art]. / Interdisziplinäre neurovaskuläre Netzwerke: eine Standortbestimmung.

BACKGROUND: In order to treat the complete spectrum of neurovascular diseases at a high level of quality, which goes beyond the purely acute treatment of stroke, the German Stroke Society (DSG) together with the German Societies for Neurosurgery and Neuroradiology developed a certification procedure for neurovascular networks (NVN). Structurally, a NVN consists of a coordinating center with at least three neurovascular network partners with a certified stroke unit. From 2018 to 2020 a total of 15 NVN have so far been audited and certified according to this new standard. OBJECTIVE: How efficient are the NVN? Are high standards maintained? MATERIAL AND METHODS: The reports of the audits were analyzed. The data were taken from the period 2017-2019. RESULTS: The 15 NVN treated a total of 86,510 stroke patients in the years examined and were networked with a total of 107 partner clinics, which were situated an average of 25 km from the coordinating center and transferred a total of 2726 patients. The coordinating centers performed 2463 thrombectomies and treated 2383 patients with nontraumatic intracerebral bleeding. In 712 patients with acute aneurysmatic subarachnoid hemorrhages endovascular treatment was carried out and clipping in 401. The audit was successful in the majority of the NVN. CONCLUSION: The certification process of NVN has been successfully established and the audits proved to be a useful instrument for quality control and improvement. The 15 NVN are highly efficient and treat more than one quarter of stroke patients in German stroke units.

[Crew resource management and simulator training in acute stroke therapy]. / Crew-Ressource-Management und Simulatortraining in der akuten Schlaganfalltherapie.

BACKGROUND: Time is of critical importance in acute stroke management. The establishment of thrombectomy now adds to the complexity and interdisciplinarity of the initial phase. In non-medical high-fidelity situations, such as aviation, crew resource management (CRM) has proven to be highly efficient. It has therefore also been implemented in professional cardiovascular life support training. In a setting where every minute counts, CRM and regular training of the high-fidelity stroke team could offer ways to improve treatment of acute stroke patients. OBJECTIVES: We evaluated the effects of a CRM-based stroke team with regular simulation training on the quality of care (e.g. door to needle time and thrombolysis rate) as well as on staff satisfaction and perceived patient safety in the emergency department of a tertiary care neurocenter. MATERIAL AND METHODS: We implemented a dedicated stroke team consisting of 7 persons who are notified by a collective call via speed dial and conceived a simulator-based team training for all new stroke team members which we conduct at monthly intervals. We recorded door to needle times of all consecutive patients, staff satisfaction in the emergency room and the acceptance of this new learning format. RESULTS: This approach led to a relevant and sustained reduction of the mean door to needle time to less than 30 min. It improved perceived patient safety in residents with professional experience of less than 2 years. There was a very high acceptance within the stroke team training and staff and its usefulness was judged to be very high. CONCLUSION: Even though our data do not allow positive effects on patient outcomes to be inferred, the implementation of a CRM-based stroke team and simulator training has had multiple positive effects on the workflow and work satisfaction in the treatment of acute stroke patients.

Patient Confidence and Information Preferences During the Treatment Decision-making Process: Results From a Large Multiple Myeloma Patient Survey Across 12 Countries in Europe and Israel.

BACKGROUND: The relapsing nature of multiple myeloma (MM) means that patients typically receive different and multiple lines of therapy, requiring many treatment decisions over the disease course. The aim of this study was to explore patient confidence and information preferences during the treatment decision-making process. PATIENTS AND METHODS: A multinational, cross-sectional survey enrolled patients with MM. It was co-developed and distributed by Myeloma Patients Europe across 12 countries in Europe and Israel from May 2019 to March 2020. Eligibility criteria included a self-reported diagnosis of MM and being able to recall the decision-making process at the start of their latest treatment line. RESULTS: A total of 1559 patients were included, with complete responses received from 1081 (69%) patients. The median age range was 54 to 64 years; there was an equal gender split and 57% had their latest treatment decision made within the past year. Overall, 54% of patients felt "very confident" in the latest treatment decision. Patients deemed the most important information to be safety/tolerability and treatment effectiveness, but the latter was among the least frequently received. Most patients reported that their primary physician treating MM was their main source for all types of information (range, 62%-94%), with 87% of patients reporting a "very good" or "good" relationship with them. CONCLUSION: Over half of patients felt very confident in their latest treatment decision; however, patients reported not routinely receiving important treatment effectiveness information. Addressing the discrepancies between information that patients receive and consider important may enhance confidence in decision-making.

Time trends in systemic thrombolysis in a large hospital-based stroke registry.

BACKGROUND: Systemic thrombolysis for acute stroke was approved by German authorities in 2002. While recombinant tissue plasminogen activator (rtPA) use first remained low, systemic thrombolysis is nowadays an established part of common stroke care. The purpose of this study was to determine changes in systemic thrombolysis rates within an observation period of 7 years following the approval of rtPA therapy in Germany in a large state-wide stroke data set. METHODS: We analyzed a prospective hospital-based stroke registry covering the entire federal state of Hesse, Germany. All hospitals providing stroke care in Hesse (neurology hospitals and hospitals for internal medicine) are obligated to register all inpatients. All cases admitted between 2003 and 2009 with a final diagnosis of ischemic stroke (ICD-10: I63) were selected. We analyzed the relationship between thrombolysis rates, onset-to-admission time (hospital arrival ≤3 and >3 h after symptom onset), patient age (quartiles and dichotomized in ≤80 and >80 years) and disability at admission (assessed by the Rankin Scale). A one-way ANOVA with Bonferroni correction for multiple comparisons was performed to test for significant changes during the observation period. RESULTS: 88,340 patients with ischemic stroke were identified. Thrombolysis rates increased continuously from 2.5% in 2003 to 8.4% in 2009. In patients admitted within 3 h after symptom onset, the thrombolysis rate was 2.5-fold higher in 2009 (25.4%) as compared to 2003 (10.5%). The mean age (±SD) of thrombolyzed patients increased from 68.7 (±11.5) years in 2003 to 70.7 (±13.4) years in 2009 (p for trend = 0.014), but remained stable in the entire cohort. 20.1% of all systemic thrombolytic treatments were performed in patients >80 years old. Disability at admission decreased more pronouncedly in rtPA-treated patients (Rankin Scale score 0-2: 15.2% in 2003 and 24.5% in 2009; p for trend <0.001) as compared to the entire cohort (34.5% in 2003 and 41.5% in 2009; p for trend <0.001). CONCLUSIONS: Thrombolytic therapy is increasingly used in acute stroke, particularly in patients admitted within the 3-hour time window. Higher treatment rates are at least partially explained by spreading rtPA application, including older and less severely affected patients. Approximately one fifth of all rtPA treatments were given to the very old (>80 years), which is outside the age limit for rtPA approval. In the light of upcoming demographic changes, the proportion of very aged stroke patients will increase substantially, further tightening the current discussion of an upper age limit for thrombolytic therapy.

Operating experiences with a molten carbonate fuel cell at Stuttgart-Möhringen wastewater treatment plant.

Fuel cells on wastewater treatment plants are a relatively new technology to convert biogas from anaerobic digestion into thermal and electrical energy. Since the end of 2007, a type of MCFC fuel cell (>250 kW(el), 180 kW(th)) has been installed at Stuttgart-Möhringen wastewater treatment plant. The goals of this research project are to raise the power self-sufficiency in Stuttgart-Möhringen, to further optimise high temperature fuel cells using biogas and to gain practical experience. After approximately 9,000 h of operation, a mean electrical 'gross'-efficiency of 44% was achieved. To fully exploit this high electrical efficiency, it is essential to keep the energy consumption of peripheral devices (gas pressure unit, gas cleaning unit, etc.) of the fuel cell as low as possible.

Effect of pH control strategies and substrate concentration on the hydrogen yield from fermentative hydrogen production in large laboratory-scale.

A series of batch experiments investigating two different pH control strategies, initial pH adjustment and continuous pH control, have been carried out in large laboratory-scale reactors with working volumes of 30 L. In both cases, pH was varied between 5 and 7.5. Sucrose concentrations were also varied starting from 0 up to 30 g/L. Higher hydrogen production yields can be achieved by batch experiments through continuous pH control than by simple initial pH adjustment. In the case of continuous pH control, maximization of hydrogen yield was acquired for slightly acidic pH of 6.5. Continuous pH control in the neutral pH range of 7.0 and in pH lower than 6.5, induced a reduction in the hydrogen production yield. Sucrose can be completely degraded only for a pH higher than 6. Lower pH values seem to inhibit the hydrogen-producing bacteria. Under the conditions of continuous pH adjustment at pH 6.5 and a sucrose concentration of 25 g/L the maximum hydrogen yield of 1.79 mol H(2)/mol hexose was obtained. These conditions could be applied for the batch start-up of large fermentors.

[Spontaneous subarachnoid hemorrhage]. / Spontane Subarachnoidalblutung.

The diagnosis, management and long-term implications of non-traumatic subarachnoid hemorrhage continue to be a multidisciplinary challenge. Often, the patients present to emergency or primary care physicians not particularly experienced in the differential diagnosis of headache. In most cases of a proven hemorrhage (aneurysm rupture in 85%), further treatment will require the discussion between experienced neurosurgeons and neuroradiologists whether to "clip or coil". Thus, subarachnoid hemorrhage is the first cerebrovascular disorder where a multidisciplinary approach has become the evidence-based standard of care. Patients with this condition are relatively young, and the survivors have a good life expectancy. Their neurologic, cognitive and psychiatric morbidity, risk of recurrent bleeding and elevated risk of other vascular diseases remain underestimated tasks for long-term care.

Management of Patients with Relapsed and/or Refractory Multiple Myeloma Treated with Novel Combination Therapies in Routine Clinical Practice in Germany.

INTRODUCTION: Multiple myeloma remains an incurable plasma cell malignancy which, despite improvements in overall survival over the last decade, is characterized by recurrent relapse and is associated with a poor prognosis. This study investigates the use of novel agents in current real-world clinical practice in the management of relapsed and/or refractory multiple myeloma (RRMM) in Germany over different lines of therapy. METHODS: A retrospective chart review was conducted for patients with RRMM treated at multiple centers across Germany between May 2017 and June 2018. Variables included patient demographics and clinical characteristics, current and prior treatment regimens, treatment response, cytogenetic abnormalities, testing methodology, and resource utilization. RESULTS: Data were analyzed from 484 patients from 47 centers across Germany (60% male; average age over 70 years; majority at International Staging System stage 2 or 3). Bone pain and anemia were the most common symptoms at diagnosis, with 63% of patients receiving osteoprotective drugs. Approximately one-third (32%) of patients had received autologous stem cell transplantation and approximately 70% underwent cytogenetic testing. After failure to respond to first-line treatment, most patients received regimens containing second-generation proteasome inhibitors and monoclonal antibodies, with overall response rates greater than 90% in second line (95% and 90% for daratumumab-based and carfilzomib-based therapies, respectively). The incidence of unplanned hospitalization ranged from 11% to 16% across all treatment lines, with longer hospital stays required for treatment administration than for treatment-related toxicity. CONCLUSION: Although treatment patterns for RRMM in Germany differ by line of therapy and are adapted as disease progresses, patients mostly receive combination regimens with carfilzomib or daratumumab in second and third lines, with high overall response rates achieved in all lines.

Upper respiratory tract disease in captive orangutans (Pongo sp.): prevalence in 20 European zoos and predisposing factors.

BACKGROUND: Upper respiratory tract disease (URTD) is a significant cause of morbidity in captive orangutans (Pongo abelii, Pongo pygmaeus), and the pathogenesis is often unknown. METHODS: The prevalence of respiratory disease in captive European orangutans (201 animals; 20 zoos) and possible predisposing factors were investigated. RESULTS: Bornean orangutans (P. pygmaeus) showed chronic respiratory signs significantly more often (13.8%) than Sumatran (P. abelii; 3.6%), and males (15.8%) were more often afflicted than females (3.9%). Hand-reared animals (21%) developed air sacculitis more often than parent-reared animals (5%). Diseased animals were more often genetically related to animals with respiratory diseases (93%) than to healthy animals (54%). None of the environmental conditions investigated had a significant effect on disease prevalence. CONCLUSION: Results suggest a higher importance of individual factors for the development of URTD than environmental conditions. Bornean, male and hand-reared orangutans and animals related to diseased animals need increased medical surveillance for early detection of respiratory disease.

[Unruptured intracranial aneurysms]. / Unrupturierte intrakranielle Aneurysmen.

The incidental discovery of an asymptomatic intracranial arterial aneurysm is no longer uncommon. It can change a person's life. Decision-making should be guided by a thorough comparison of the risks associated with the natural course and with microsurgical or endovascular intervention. At present this comparison will favor a conservative approach in the majority of patients, especially in those with small aneurysms or who are over 50 years old.

A new concept for the differential diagnosis and therapy of anaemia in cancer patients.

PURPOSE: This study aimed to prove the usefulness of the diagnostic plot, using the haemoglobin content of reticulocytes as a measure of functional iron deficiency (FID) and the ferritin index as a measure of iron availability, to customise anaemia treatment in cancer patients. METHODS: Based on results of this plot, cancer patients fulfilling practice guideline criteria to receive erythropoiesis-stimulating agents (ESAs) were allocated to treatment with ESAs alone, iron alone or the combination of both. Primary endpoint was the percentage of patients identified to require iron in addition or as an alternative to ESA therapy. RESULTS: Out of 303 patients screened, 286 were allocated to treatment: 204 patients were normochromic and iron replete and treated with ESAs alone, 22 had both FID and anaemia of chronic disease and were treated with ESAs and parenteral iron, and 60 were iron-depleted and treated with iron only. After 8 weeks, a haemoglobin increase >1 g/dL from baseline was shown by 56% of patients treated with ESAs alone, by 100% of patients receiving the combination, by 50% of normochromic and by 73% of hypochromic iron-depleted patients receiving iron only. Acute phase reaction did not diminish the response rate to ESAs. CONCLUSIONS: The diagnostic plot was superior to transferrin saturation and ferritin in predicting iron availability in hypochromic patients treated with ESAs and proved useful to select treatment for anaemia in cancer patients.

Patient Characteristics and Outcomes of Relapsed/Refractory Multiple Myeloma in Patients Treated with Proteasome Inhibitors in Germany.

INTRODUCTION: Real-world data reflects treatments and outcomes in clinical practice in contrast with controlled clinical trials. This study evaluates real-life multiple myeloma (MM) patients receiving proteasome inhibitor (PI)-based treatments in the second or third therapy line in 2017 in Germany. METHODS: This is a retrospective chart review on adult relapsed/refractory MM patients treated with ≥1 dose of a PI-based regimen in either the second or the third line of therapy. Participating physicians had ≥3 years of clinical experience in treating symptomatic MM patients and used PI according to the label. RESULTS: Distinct patient profiles for each PI-based regimen emerged. Younger, fitter, transplant-eligible patients received novel PI triplets such as carfilzomib in combination with lenalidomide and dexamethasone (KRd) or IRd. Patients receiving lenalidomide in first-line therapy mostly received lenalidomide-free regimens in second-line therapy. In high-risk patients, no clear treatment patterns could be ascertained. The complete response rates were highest with KRd (13.0%), followed by carfilzomib in combination with dexamethasone (Kd) (5.7%) and bortezomib (4.8%). The very good partial response rates were highest with IRd (76.9%), followed by KRd (53.7%), Kd (25.7%), and bortezomib (20.5%). None of the KRd- or IRd-treated patients responded below a partial response. DISCUSSION/CONCLUSION: Clear patient profiles for each PI type were observed. In second-line therapy, younger, fitter, transplant-eligible patients received novel-PI-based triplets, e.g., KRd or IRd. Patients treated with lenalidomide in first-line therapy mostly received lenalidomide-sparing regimens in second-line therapy. In high-risk patients no clear treatment patterns could be ascertained due to the limited sample size.

In vivo evidence of structural brain asymmetry in musicians.

Certain human talents, such as musical ability, have been associated with left-right differences in brain structure and function. In vivo magnetic resonance morphometry of the brain in musicians was used to measure the anatomical asymmetry of the planum temporale, a brain area containing auditory association cortex and previously shown to be a marker of structural and functional asymmetry. Musicians with perfect pitch revealed stronger leftward planum temporale asymmetry than nonmusicians or musicians without perfect pitch. The results indicate that outstanding musical ability is associated with increased leftward asymmetry of cortex subserving music-related functions.

Collection and analysis of breath and breath condensate exhaled by feral pigeons (Columba livia) and chickens (Gallus domesticus).

Samples of exhaled breath and breath condensate were collected from 20 feral pigeons (Columba livia) while they were anaesthetised and intubated, and when they were kept unanaesthetised in an acrylic box. Samples were also collected from six chickens (Gallus domesticus) while they were kept in an acrylic box. The samples were analysed for pH, nitric oxide (NO), hydrogen peroxide and leukotriene B4. The volume of condensate collected from the pigeons was independent of bodyweight and significantly more (1.66 [0.64] ml/kg) was obtained while they were in the acrylic box than when they were intubated (0.87 [0.32] ml/kg). The mean volume collected from the chickens was 0.15 (0.06) ml/kg. Cooled samples had higher concentrations of NO than uncooled samples. The pH of the samples of condensate collected from birds in the acrylic box were significantly higher (7.9 [0.3]) than those from the intubated birds (5.3 [0.1]), and samples from the chickens had significantly higher pH values than samples from the pigeons (8.2 [0.2] v 7.9 [0.3]).

Development of instrumentation systems as a base for control of digestion process stability in full-scale agricultural and industrial biogas plants.

This article deals with the analysis of instrumentation from three modern German full-scale biogas plants with different inputs and typical process engineering concepts for German conditions. The measured results from each plant and the suitability of the instrumentation used are evaluated and assessed. Conclusions are also made about improving the use and architecture of the instrumentation. The analysis results show which benefits and optimum combination of on-line and off-line instrumentation could result for the control and automation of industrial and agricultural biogas plants.

Optimisation potential for a SBR plant based upon integrated modelling for dry and wet weather conditions.

Integrated dynamic simulation analysis of a full-scale municipal sequential batch reactor (SBR) wastewater treatment plant (WWTP) was performed using the KOSMO pollution load simulation model for the combined sewer system (CSS) and the ASM3 + EAWAG-BioP model for the WWTP. Various optimising strategies for dry and storm weather conditions were developed to raise the purification and hydraulic performance and to reduce operation costs based on simulation studies with the calibrated WWTP model. The implementation of some strategies on the plant led to lower effluent values and an average annual saving of 49,000 euro including sewage tax, which is 22% of the total running costs. Dynamic simulation analysis of CSS for an increased WWTP influent over a period of one year showed high potentials for reducing combined sewer overflow (CSO) volume by 18-27% and CSO loads for COD by 22%, NH(4)-N and P(total) by 33%. In addition, the SBR WWTP could easily handle much higher influents without exceeding the monitoring values. During the integrated simulation of representative storm events, the total emission load for COD dropped to 90%, the sewer system emitted 47% less, whereas the pollution load in the WWTP effluent increased to only 14% with 2% higher running costs.

Historical review: a short history of German neurology - from its origins to the 1940s.

This paper aims at reconstructing the development and role of German neurology between 1840 and 1940. Therefore a couple of original sources as well as selected material form the scattered secondary literature were assessed and reviewed. Since the middle of the nineteenth century, an intricate process of separation from internal medicine and psychiatry gradually led to forming a self-conscious community of German neurologists. While Moritz Heinrich Romberg had constructed a cognitive basis for neurology, scientific founders such as Wilhelm Erb, Carl Wernicke, Alois Alzheimer, Hermann Oppenheim, Max Nonne, and many others established the new discipline within modern medicine. In 1891, the first generation of "pure" neurologists succeeded in founding the German Journal for Neurology (Deutsche Zeitschrift für Nervenheilkunde) followed by an autonomous professional organisation, the Society of German Neurologists (Gesellschaft Deutscher Nervenärzte) in 1907. A variety of external factors, however, hampered the institutional evolution and thus the implementation of chairs and departments remained quite modest. In 1935, only 2 years after the National Socialists had seized power, the regulatory merger with the psychiatrists' society caused the cautious attempts of German neurologists for autonomy to end in complete failure. The imprisonment, murder and expulsion of neuroscientists declared as Jewish or non-Aryan caused profound changes in neurology, medicine, academic life, and health care in general. Further historical research is needed to reconstruct in detail the involvement of German neurologists in racial-hygienic and eugenic research as well as the institutional and scientific development of German neurology after World War II.