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BACKGROUND/OBJECTIVES: Liver disease is associated with altered serum osmolality, increased thrombin generation, and systemic inflammation, all of which may contribute to perihematomal edema (PHE) after intracerebral hemorrhage (ICH). We evaluated the association between a validated liver fibrosis index and PHE growth in a cohort of patients with primary ICH. METHODS: We performed a retrospective cohort study using data from the Virtual International Stroke Trials Archive-ICH. We included adult patients with primary ICH presenting within 6 hours of symptom onset. The exposure of interest was the Fibrosis-4 (FIB-4) score, a validated liver fibrosis index; this was modeled as a continuous variable. The primary outcome was absolute PHE growth over 96 hours. Secondary outcomes were absolute admission and 96-hour PHE volumes. We used multiple linear regression models adjusted for established determinants of PHE. In a secondary analysis, the FIB-4 score was modeled as a categorical variable to compare patients with versus without liver fibrosis. RESULTS: Among 354 patients with ICH, 8% had evidence of liver fibrosis based on a validated cut-off. The FIB-4 score was not associated with PHE growth in unadjusted (β, 0.03; 95% CI, −0.01–0.12) or adjusted models (β, 0.04; 95% CI, −0.03–0.13). In a secondary analysis treating FIB-4 as a categorical variable, patients with liver fibrosis did not have greater PHE growth than those without liver fibrosis. FIB-4 score was also not associated with absolute admission or 96-hour absolute PHE volumes. CONCLUSIONS: In a multicenter cohort of patients with primary intracerebral hemorrhage, a liver fibrosis score was not associated with PHE volume or growth.

Melanoma, an aggressive skin cancer originating from melanocytes, can metastasize to the lungs, liver, cortex, femur, and spinal cord, ultimately resulting in DNA mutagenic effects. Melatonin is an endogenous hormone and free radical scavenger that possesses the ability to protect the DNA and to exert anti-proliferative effects in melanoma cells. The aim of this study was to evaluate the effects of B16F10 melanoma cells and the effects of melatonin supplementation on genotoxic parameters in murine melanoma models. Thirty-two male C57Bl/6 mice were divided in the following four groups: PBS + vehicle (

Das Nierenzellkarzinom ist der dritthaufigste Tumor auf dem urologischen Fachgebiet. Die Therapie kleinerer Tumoren besteht zunehmend in organerhaltenden Ansatzen wie der partiellen Nephrektomie, fokalen Ablation mittels Kryoablation oder Radiofrequenzablation oder auch der aktiven Uberwachung. Diese Therapieformen erhohen die Anforderungen an eine Tumornachsorge. Wie sind die aktuellen Empfehlungen zur Nachsorge des Nierenzellkarzinoms aufgrund der neuen Therapiemoglichkeiten? In der vorliegenden Arbeit werden die verschiedenen tumorbiologischen Aspekte, die diagnostischen Moglichkeiten der Tumornachsorge sowie die Empfehlungen der verfugbaren Leitlinien (S3-Leitlinie, EAU-Leitlinie [European Association of Urology] und AUA-Leitlinie [American Urological Association]) dargestellt. Die Nachsorge des Nierenzellkarzinoms ist nicht sehr standardisiert, insbesondere weil die Datenlage begrenzt ist. Prinzipiell sollte die Nachsorge in den ersten 3 Jahren nach der erfolgten Therapie und bei Patienten mit einem erhohten Rezidivrisiko intensiver vorgenommen werden. Fur die Risikoeinteilung stehen mehrere Prognosemodell zur Verfugung, die ausschlieslich auf klinischen Parametern basieren. Bisherige Empfehlungen zur Nachsorge des Nierenzellkarzinoms basieren auf retrospektiven Analysen. Zukunftige Nachsorgestrategien sollten (noch zu bestimmende) Marker einschliesen und prospektiv gepruft werden.

Contains fulltext : 249977.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as β blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; p(interaction)=0·18). A similar result was seen for β blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; p(interaction)=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus β blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; p(interaction)=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.

Due to their high prevalence, Parkinson's syndromes are exemplary geriatric syndromes. In addition to idiopathic Parkinson's disease, drug-induced and vascular Parkinson's syndromes are especially relevant in older age. A comprehensive anamnesis, thorough clinical neurological examination and rational additional diagnostics ensure the correct differential diagnostic classification. The multidimensional geriatric assessment is used to quantify the syndrome-specific ability impairments. The primary therapeutic objective in old age is the preservation of everyday competences. Drug treatment is centered around L‑dopa because of its favorable effect-side effect ratio. In cases of motor fluctuations, entacapone, opicapone or safinamide can be added, whereas dopamine agonists are generally unsuitable. Rivastigmine is indicated in mild to moderate Parkinson's dementia and furthermore can possibly improve gait stability. Speech therapy, as well as physical and occupational therapy, including the Parkinson's disease-specific Lee Silverman voice treatment are indispensable components of the multiprofessional treatment concept.

The diagnosis of visceral leishmaniasis (VL) presents problems due to the toxicity and/or high cost of drugs. In addition, no vaccine exists to protect against human disease. In this study, the antigenicity and immunogenicity of amastin protein were evaluated in L. infantum–infected dogs and humans. For the diagnosis, besides the recombinant protein, 1 linear B-cell epitope was synthetized and evaluated in serological assays. Results showed high sensitivity and specificity values to detect the disease when both antigens were employed against a canine and human serological panel. By contrast, when using rA2 and a soluble Leishmania antigenic preparation, sensitivity and specificity values proved to be lower. A preliminary immunogenicity study showed that the amastin protein induced high IFN-γ and low IL-10 production in stimulated PBMC derived from treated VL patients and healthy subjects, thus suggesting a potential use of this protein as an immunogen to protect against human disease.

Purpose/Objective(s): The COVID-19 pandemic has direct and indirect impact on patients with cancer. Low- and middle-income regions, especially sub-Saharan Africa, are especially vulnerable to a negative impact on cancer resources and outcomes. We report the initial indirect impact of COVID-19 on cancer care in the sub-Saharan Africa region approximately 14 months into the pandemic. Materials/Methods: At the start of the pandemic, we created a consortium of African and North American cancer centers and NGOs for the distribution of factual and timely information and data on COVID-19 and cancer care. A survey was distributed to consortium members and other colleagues from the sub-Saharan Africa region to understand the impact of COVID-19 in cancer care resources. Survey respondents represent cancer experts from 8 centers in Ghana, Nigeria, Kenya, Ethiopia, South Africa, Rwanda, and Zimbabwe. Results: All sites report SARS-COv-2 transmission amongst cancer patients and staff. A total of 48 staff developed COVID-19 infection with one site reporting a single death. Additionally, 62.5% of sites report loss of oncology physician or nursing staff due to redeployment for COVID-19 care resulting in minimal (20%), moderate (60%), or other (20%) impact on cancer care. All 8 sites report a government mandated lockdown with a median duration of 2.3 months (IQR.9-4.2 months). Impact of the lockdown on cancer care was reported as none (12.5%), minimal (12.5%), moderate (50%) and severe (25%). Additionally, we surveyed the impact of COVID-19 on resources in radiation, medical and surgical oncology services. A total of 25% of responders reported decreases in radiation resources while 37.5% reported changes in medical and surgical oncology resources. For radiation oncology, the most common impact was access to CT imaging for 3D-conformal planning (25%), access to brachytherapy (12.5%), and medical physics support (12.5%). For medical oncology, the most frequent impact was access to chemotherapy (37.5%) and blood products (12.5%), and loss of oncology ward space (12.5%). The most frequent impact for surgical oncology was access to operating rooms (37.5%), ventilators (12.5%), anesthesia (25%), blood products (25%), and other supply chain issues (25%). Of centers who reported impact on cancer care, severity of impact was none (50%) and moderate (50%) for radiation oncology;mild (25%) and moderate (75%) for medical oncology;and moderate (75%) and severe (25%) for surgical oncology. Conclusion: Our survey identified diffuse impact of COVID-19 on all facets of cancer care across sub-Saharan Africa. Based on physician assessment of impact, the discipline of surgical oncology may be impacted the greatest. Additional studies measuring the impact of COVID-19 on cancer outcomes are ongoing.

Searching for quantum functionalities requires access to the electronic structure, constituting the foundation of exquisite spin-valley–electronic, topological, and many-body effects. All-optical band-structure reconstruction could directly connect electronic structure with the coveted quantum phenomena if strong lightwaves transported localized electrons within preselected bands. Here, we demonstrate that harmonic sideband (HSB) generation in monolayer tungsten diselenide creates distinct electronic interference combs in momentum space. Locating these momentum combs in spectroscopy enables super-resolution tomography of key band-structure details in situ. We experimentally tuned the optical-driver frequency by a full octave and show that the predicted super-resolution manifests in a critical intensity and frequency dependence of HSBs. Our concept offers a practical, all-optical, fully three-dimensional tomography of electronic structure even in microscopically small quantum materials, band by band.

Die Etablierung qualitatssichernder Masnahmen im Krankenhaus hat in den vergangenen Jahren zunehmende Bedeutung erlangt. Zielstellung ist es, die Behandlungsqualitat durch Erkennung und konsekutive Vermeidung von Behandlungsfehlern zu verbessern. Ziel der Arbeit ist die Erlauterung des Peer-Review-Verfahrens als geeignetes Verfahren der Qualitatsverbesserung sowie Darstellung eines objektiv messbaren Effekts dieser Intervention auf die Behandlungsqualitat. Nach Definition von Qualitatsparametern zur Identifizierung von Patientenverlaufen mit Verbesserungspotenzial wurde primar durch die Helios-Klinikgruppe und seit 2008 ubergreifend durch die Initiative Qualitatsmedizin (IQM) das Peer-Review-Verfahren entwickelt, in dem externe Peers in einer retrospektiven Patientenaktenanalyse aus der Ex-ante-Sicht nach Verbesserungspotenzial im Behandlungsprozess suchen, dieses in einem kollegialen Fachdialog diskutieren, Losungsansatze besprechen und daraus konkrete Masnahmen abgeleitet werden. Uber das dargestellte Verfahren konnen Patientenrisiken und Fehler im Behandlungsverlauf erkannt und konsekutiv vermieden werden. Als objektiv messbarer Ausdruck der verbesserten Behandlungsqualitat konnte eine Senkung der indikationsbezogenen In-house-Mortalitat fur verschiedene Erkrankungen belegt werden. Das Peer-Review-Verfahren reprasentiert als systematischer kollegialer Austausch auf Augenhohe die beste Form arztlicher Qualitatssicherungsmasnahmen.

Background and Purpose— Observational data suggest that antiplatelet therapy after intracerebral hemorrhage (ICH) alleviates thromboembolic risk without increasing the risk of recurrent ICH. Given the paucity of data on the relationship between antiplatelet therapy after ICH and functional outcomes, we aimed to study this association in a multicenter cohort. Methods— We meta-analyzed data from (1) the Massachusetts General Hospital ICH registry (n=1854), (2) the Virtual International Stroke Trials Archive database (n=762), and (3) the Yale stroke registry (n=185). Our exposure was antiplatelet therapy after ICH, which was modeled as a time-varying covariate. Our primary outcomes were all-cause mortality and a composite of major disability or death (modified Rankin Scale score 4–6). We used Cox proportional regression analyses to estimate the hazard ratio of death or poor functional outcome as a function of antiplatelet therapy and random-effects meta-analysis to pool the estimated HRs across studies. Additional analyses stratified by hematoma location (lobar and deep ICH) were performed. Results— We included a total of 2801 ICH patients, of whom 288 (10.3%) were started on antiplatelet medications after ICH. Median times to antiplatelet therapy ranged from 7 to 39 days. Antiplatelet therapy after ICH was not associated with mortality (hazard ratio, 0.85; 95% CI, 0.66–1.09), or death or major disability (hazard ratio, 0.83; 95% CI, 0.59–1.16) compared with patients not started on antiplatelet therapy. Similar results were obtained in additional analyses stratified by hematoma location. Conclusions— Antiplatelet therapy after ICH appeared safe and was not associated with all-cause mortality or functional outcome, regardless of hematoma location. Randomized clinical trials are needed to determine the effects and harms of antiplatelet therapy after ICH.

The ever-increasing global demand for energy is leading to a progressive expansion of HVDC transmission lines. The cables and cable accessories required for this pose major challenges for the respective manufacturers concerning the production and testing of these types of equipment. In addition to DC voltage tests, the electrical design must also be able to withstand AC tests. Beside factory testing, special precautions have to be taken for on-site testing, to provide an equivalent test power of >500 Mvar at 50 Hz through modular test equipment configured for optimal test performance. On-site tests have to be carried out after the entire cable system has been installed, as well as after repair work. Both cases pose significant technical and logistical challenges.

As conventional electronic is approaching its fundamental limits, huge efforts have been taken to explore new concepts of ultrafast control at the quantum level. Lightwave electronics — the foundation of attosecond science [1] — has opened a spectacular perspective by utilizing the carrier wave of an intense light pulse to steer the translational motion of charges faster than a single cycle of light [1–4]. Despite their promising potential as future information carrier, the electron's internal quantum attributes such as the spin and the valley pseudospin [5] have not been switchable at optical clock rates.

The demand to transport electric energy over large distances increases further. To fulfill this task, the rated DC voltages increased within the last decade. HVDC systems up to 800 kV are in operation and higher transmission voltages are under development. All HVDC equipment, e.g. HVDC valves, transmission lines (air or cables), HVDC transformers, bushings, insulators etc. have to be tested. To perform these development tests, type tests, routine tests and on-site tests, special HVDC and UHDC test systems are needed. This is only realizable with adequate test systems which have to operate at higher voltage levels than the rated voltages of the components to be tested. In doing this, DC test equipment are operating near at the physical and technical limits. This is because DC test equipment does not have to withstand pure DC voltages and currents. In case of a breakdown or flashover of the device under test, the DC test system has to withstand these high transient voltages, often followed by fast polarity changes. Therefore, the electrical field distribution, which mainly is controlled by a resistive field distribution (DC current plus space charges and surface charges), will be overlaid by a (fast) capacitive field distribution, which is in some cases opposite to the resistive field distribution.Area and space restrictions within test fields, the occurrence of fast transients (like in bushings filled with SF6), in combination with surface and space charges lead to very high and complex field stress of the DC test equipment. This implies strong electrical stress on the DC test system and the used materials.This paper will present some examples of special designed DC test equipment. Demanded DC test voltages reach 2000 kV or even more. Thus a realized DC test system with rated voltage of 2000 kV and with a DC current of 100 mA will be described. A concept how to protect the test object and the HV source, like DC-Generator and Impulse Generator used for combined voltage tests, will also be presented.In addition, the need of mobile test systems to perform on-site tests on cables and other HVDC components increases also. Main task here is to handle the field distribution under different environmental conditions and to realize a very compact and robust design. Finally, when testing long DC cables, the safe and reproducible discharging of these long cables is another issue. How to solve this task safe with adequate mobile DC test systems and discharging devices will be presented in this contribution also.

Background: Leishmaniases are neglected diseases caused by infection with Leishmania parasites and there are no human vaccines in use routinely. The purpose of this study was to examine the immunogenicity of ChimeraT, a novel synthetic recombinant vaccine against visceral leishmaniasis (VL), incorporated into a human-compatible liposome formulation. Methods: BALB/c mice were immunized subcutaneously with ChimeraT/liposome vaccine, ChimeraT/saponin adjuvant, or ChimeraT/saline and immune responses examined in vitro and in vivo. Results: Immunization with the ChimeraT/liposome formulation induced a polarized Th1-type response and significant protection against L. infantum infection. ChimeraT/liposome vaccine stimulated significantly high levels of interferon (IFN)-&gamma, interleukin (IL)-12, and granulocyte macrophage-colony stimulating factor (GM-CSF) cytokines by both CD4 and CD8 T-cells, with correspondingly lower levels of IL-4 and IL-10 cytokines. Induced antibodies were predominantly IgG2a isotype, and homologous antigen-stimulated spleen cells produced significant nitrite as a proxy for nitric oxide (NO). Furthermore, we examined a small number of treated VL patients and found higher levels of circulating anti-ChimeraT protein IgG2 antibodies, compared to IgG1 levels. Conclusions: Overall, the liposomal formulation of ChimeraT induced a protective Th1-type immune response and thus could be considered in future studies as a vaccine candidate against human VL.

The control measures against visceral leishmaniasis (VL) include a precise diagnosis of disease, the treatment of human cases, and reservoir and vector controls. However, these are insufficient to avoid the spread of the disease in specific countries worldwide. As a consequence, prophylactic vaccination could be interesting, although no effective candidate against human disease is available. In the present study, the Leishmania infantum amastin protein was evaluated regarding its immunogenicity and protective efficacy against experimental VL. BALB/c mice immunized with subcutaneous injections of the recombinant protein with or without liposome/saponin (Lip/Sap) as an adjuvant. After immunization, half of the animals per group were euthanized and immunological evaluations were performed, while the others were challenged with L. infantum promastigotes. Forty-five days after infection, the animals were euthanized and parasitological and immunological evaluations were performed. Results showed the development of a Th1-type immune response in rAmastin-Lip and rAmastin-Sap/vaccinated mice, before and after infection, which was based on the production of protein and parasite-specific IFN-γ, IL-12, GM-CSF, and nitrite, as well as the IgG2a isotype antibody. CD4+ T cells were mainly responsible for IFN-γ production in vaccinated mice, which also presented significant reductions in parasitism in their liver, spleen, draining lymph nodes, and bone marrow. In addition, PBMC cultures of treated VL patients and healthy subjects stimulated with rAmastin showed lymphoproliferation and higher IFN-γ production. In conclusion, the present study shows the first case of an L. infantum amastin protein associated with distinct delivery systems inducing protection against L. infantum infection and demonstrates an immunogenic effect of this protein in human cells.

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.

In the present study, a conserved Leishmania hypothetical protein, LiHyE, was evaluated for the serodiagnosis of leishmaniasis. Results showed that it presented high sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to serologically identify visceral leishmaniasis (VL) dogs when 40 positive sera and 95 cross-reactive samples were used. rLiHyE also showed the best results of sensitivity, specificity, PPV, and NPV to identify tegumentary leishmaniasis (TL) and VL patients when 45 leishmaniasis patients' sera and 90 cross-reactive samples were used. Results were better in comparison to those obtained when rA2 or Leishmania antigenic extract was employed as controls. The posttreatment follow-up showed that rLiHyE-specific antibodies declined significantly after the end of treatments, and a predominance of the IgG2 subclass was found in comparison to IgG1 levels in both TL and VL patients. In conclusion, rLiHyE can be considered a candidate for the serodiagnosis of canine and human leishmaniasis.

Background and Purpose— Perihematomal edema (PHE) is associated with poor outcomes after intracerebral hemorrhage (ICH). PHE evolves in the early period after ICH, providing a therapeutic target and window for intervention. We studied the effect of PHE volume expansion in the first 72 hours (iPHE) and its relationship with functional outcomes. Methods— We used data contained in the Virtual International Stroke Trials Archive. We included patients who presented within 6 hours of symptom onset, had baseline clinical, radiological, and laboratory data, and further computed tomographic scan data at 72 hours and 90-day functional outcomes. We calculated iPHE and used logistic regression analysis to assess relationships with outcome. We adjusted for confounding variables and the primary outcome measure poor day-90 outcome (defined as modified Rankin Scale score of ≥3. We performed subgroup analyses by location and by volume of ICH. Results— We included 596 patients with ICH. Median baseline hematoma volume was 15.0 mL (IQR, 7.9–29.2) and median baseline PHE volume was 8.7 mL (IQR, 4.5–15.5). Hematoma expansion occurred in 122 (34.9%) patients. Median iPHE was 14.7 mL (IQR, 6.6–30.3). The odds of a poor outcome were greater with increasing iPHE (OR, 1.78; CI, 1.12–2.64 per mL increase). Subgroup analyses showed that iPHE was only related to poor functional outcomes in basal ganglia and small ( Conclusions— Absolute increase in PHE during 72 hours was associated with worse functional outcomes after ICH, particularly with basal ganglia ICH and hematomas

Background. Histoplasmosis may complicate tumor necrosis factor (TNF)–α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. Methods. We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. Results. The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06–14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03–1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1–69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. Conclusions. In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.

Atomically strong multi-terahertz waves drive novel subcycle quantum motions of electrons, generating high-harmonics, dynamical Bloch oscillations, quasiparticle collisions etc. Lightwave-driven scanning tunneling microscopy allows us to take the first femtosecond movie of a single-molecule orbital.

Prevention and therapy of deep vein thrombosis and pulmonary embolisms in patients with acute stroke (ischemia and hemorrhage) represent a special challenge in the clinical routine. This article gives an overview on the epidemiology, risk factors and causes of deep vein thrombosis and pulmonary embolism in patients with acute stroke. The focus lies on the efficacy and safety of prophylactic treatment with compression stockings, compression devices and anticoagulants. Special therapeutic options in the event of symptomatic deep vein thrombosis and pulmonary embolisms in patients with intracerebral hemorrhage and increased risk of recurrent bleeding are presented.

Background Perihaematomal edema (PHE) expansion rate may be a predictor of outcome after intracerebral haemorrhage (ICH). We determined whether PHE expansion rate in the first 72 hours after ICH predicts outcome, and how it compares against other PHE measures. Methods We included patients from the Virtual International Stroke Trials Archive. We calculated PHE expansion rate using the equation: (PHE at 72 hours PHE at baseline)/(time to 72-hour CT scan time to baseline CT scan). Outcomes of interest were mortality and poor 90-day outcome (modified Rankin Scale score of ≥3). Logistic regression was used to assess relationships with outcome. Results A total of 596 patients with ICH were included. At baseline, median haematoma volume was 15.0 mL (IQR 7.9–29.2) with median PHE volume of 8.7 mL (IQR 4.5–15.5). Median PHE expansion rate was 0.31 mL/hour (IQR 0.12–0.55). The odds of mortality were greater with increasing PHE expansion rate (OR 2.63, CI 1.10 to 6.25), while the odds of poor outcome also increased with greater PHE growth (OR 1.67, CI 1.28 to 2.39). Female sex had an inverse relationship with PHE growth, but baseline haematoma volume had a direct correlation. Among other PHE measures, only interval increase in PHE correlated with poor outcome. There was no significant difference between the 2 measures of PHE volume expansion. Conclusions Rate of PHE growth over 72 hours was an independent predictor of mortality and poor functional outcomes following ICH. Baseline haematoma volume and gender appear to influence PHE growth.

Background and purpose: The etiology of hyperglycemia in acute stroke remains controversial. It is unclear whether hyperglycemia arises as an epiphenomenon of stroke or as a reflection of underlying diabetes. Autonomic shift to sympathetic overactivity has been repeatedly observed in acute stroke. We hypothesize that hyperglycemia in acute stroke relates to autonomic imbalance and that the respective deleterious effects on stroke outcome may be cross-linked. Methods: A total of 75 non-diabetic patients with ischaemic stroke were included in a prospective study. Glucose levels at admission, fasting glucose, and glucose profiles were recorded. Autonomic function was quantified by the assessment of spontaneous baroreflex sensitivity (BRS) using a cross-correlation method. Demographic and clinical data including stroke volumes and admission National Institute of Heath Stroke Scale scores were included into the analysis. Functional outcome at 90 days was assessed using the modified Rankin Scale. Results: Hyperglycemia was correlated with decreased BRS independent of stroke severity or volume (r = −0.46, P

Etwa 10–15% aller Schlaganfalle werden durch eine nichtaneurysmatische intrazerebrale Blutung (ICB) verursacht. Aufgrund der Altersstruktur der Bevolkerung ist von einer steigenden Inzidenz auszugehen. Die Mortalitat wird in Arbeiten aus den 1990er Jahren auf bis zu 50% geschatzt. Es ist jedoch zu vermuten, dass die schlechte Prognose durch eine „sich selbst erfullende Prophezeiung“ mitbedingt ist, im Rahmen derer Patienten mit ICB haufig nur eine palliative Therapie erhalten. Eine neuere Studie zeigte, dass alleine die Behandlung auf einer spezialisierten neurologischen Intensivstation mit einer Reduktion der Mortalitat assoziiert war. In den letzten Jahren wurden erhebliche Anstrengungen unternommen, Therapiekonzepte fur die intrazerebrale Blutung zu entwickeln und in randomisierten Studien zu prufen. Neben dem neurologischen Status bei Aufnahme ist das Blutungsvolumen ein entscheidender prognostischer Faktor, und die rasche Eingrenzung der Blutung wurde als wichtiger therapeutischer Ansatz identifiziert. Im Anschluss an eine vielversprechende Dosisfindungsstudie zeigte eine Phase-III-Studie zwar eine Verringerung der Hamatomzunahme nach Gabe von aktiviertem Faktor VIIa innerhalb der ersten 4 h, ein signifikanter Effekt auf das klinische Outcome konnte jedoch nicht nachgewiesen werden. Ahnliche Ergebnisse fanden sich in einer randomisierten Studie zur Blutdrucksenkung in der Akutphase. Der Beleg aus randomisierten Studien, dass eine Verminderung des Hamatomwachstums sich in einer relevanten Verbesserung des Outcomes niederschlagt, steht somit weiterhin aus. Auch der Wert der chirurgischen Therapie ist nicht abschliesend geklart. In der bisher grosten randomisierten Studie schien nur eine kleine Subgruppe der Patienten mit oberflachlich gelegener Blutung von der Ausraumung des Hamatoms zu profitieren. Diese Subgruppe wird derzeit in einer Nachfolgestudie untersucht. Ob die verbesserte intensivmedizinische Versorgung auch das funktionelle Outcome nachhaltig positiv beeinflusst, werden Daten der kommenden Jahre zeigen.

As conventional electronic is approaching its ultimate limits, tremendous efforts have been taken to explore novel concepts of ultrafast quantum control. Lightwave electronics - the foundation of attosecond science - has opened a spectacular perspective by utilizing the oscillating carrier wave of an intense light pulse to control the translational motion of the electron’s charge faster than a single cycle of light [1-7]. Despite their promising potential as future information carriers [8,10], the internal quantum attributes such as spins and valley pseudospins have not been switchable at optical clock rates. Here we demonstrate a novel subcycle control scheme of the electron’s pseudospin in a monolayer of tungsten diselenide using strong mid-infrared lightwaves [9]. Our work opens the door towards systematic valleytronic protocols at optical clock rates.

Background Cardiovascular risk in hemodialysis patients is enhanced, resulting in a higher mortality rate compared with the general population, yet the average wait time for renal transplantation in Germany is 5–7 years. The age of wait-listed patients has risen progressively. The aim of this study was to evaluate the prevalence of cardiovascular disease in patients on the waiting list in our center before and after renal transplantation as well as the extent to which invasive treatment was required in these patients. Methods The study investigated 2 groups: 350 patients on the renal transplantation waiting list at our center in 2008 and 324 patients who underwent renal transplantation at the same center in the years 2003–2007. Results In 2008, 141 women and 209 men with a mean age of 48.6 years (range 13–71 years) were on the waiting list. In the years 2003–2007, 98 women and 226 men with a mean age of 54.3 years (range 16–78 years) received renal transplants. One hundred six patients on the waiting list for renal transplantation had to undergo coronary angiography. There is no upper age limit for donors or recipients in our program. Mean age at admission on the waiting list was 48.6 years (range 13–71 years). Mean age at transplantation was 54.3 years (range 16–78 years) in our center. Most of these patients were asymptomatic but presented a risk profile that included diabetes mellitus, severe general atherosclerosis, a pathologic ergometric test, or abnormal myocardial scintigraphy. Only in 1 case could coronary heart disease be excluded. Seventy patients (20%) suffered from mild to moderate coronary heart disease without the need for intervention. In 5 patients (1.4%) coronary bypass surgery was necessary due to severe 3-vessel coronary heart disease. In 2 cases (0.6%) replacement of the aortic valve was performed because of aortic valvular stenosis. Coronary angioplasty without implantation of stents was done in 2 patients (0.6%). Twenty-two patients (6.8%) were treated with implantation of bare metal stents and 6 patients (1.7%) with drug-eluting stents. After renal transplantation, 22 patients (6.8%) suffered from peripheral arterial occlusive disease. In 58 patients, coronary heart disease was documented by angiography. 16 patients (4.9%) had 1-vessel disease, 23 patients (7%) 2-vessel disease, and 19 patients (5.8%) 3-vessel disease. Myocardial infarction was documented in 18 patients (5.5%) before and in 5 patients (1.5%) after renal transplantation. Bare metal stent implantation was performed in 6 patients (1.8%) after transplantation. One patient received a drug-eluting stent after renal transplantation. In the years 2003–2007, 22 patients underwent coronary bypass surgery before kidney transplantation. Conclusion The prevalence of coronary heart disease is high in patients on the waiting list and after renal transplantation. The majority of these patients are clinically asymptomatic. One-third of the patients with coronary heart disease had to be treated invasively. Nevertheless, many diabetic patients are very sick from multiple complications after the waiting time, making theme unsuitable for transplantation.

The exciton binding energy in GaAs-based quantum-well (QW) structures is in the range of ~10 meV, which falls in the terahertz (THz) regime. THz-induced nonlinear optical effects of excitons in QWs are of great interest because they provide new insights into the quantum coherence and wavepacket dynamics in semiconductors. For example, an experiment/theory study demonstrated that strong single-cycle THz pulses induce coherent extreme-nonlinear optical transients in semiconductor QWs, where the rotating wave approximation breaks down and the ponderomotive effects become prominent [1]. We have conducted a time-resolved study to observe the resonant interactions of strong narrowband THz pulses with coherent excitons in QWs, where the THz radiation is tuned near the 1s-2p excitonic transition and the THz pulse duration (~3 ps) is comparable with the exciton dephasing time.

Trotz einer Inzidenz von jahrlich 90.000 Fallen in der Europaischen Union und hoher Mortalitats- und Invaliditatsraten sind Pathogenese und Pathophysiologie der intrazerebralen Blutung noch immer nicht hinreichend geklart. Zahlreiche Therapieempfehlungen basieren aufgrund der geringen Anzahl kontrollierter Studien auf theoretischen Uberlegungen, Beobachtungen kleiner Patientenkollektive und personlichen Erfahrungen des behandelnden Arztes. Der vorliegende Beitrag soll unter Berucksichtigung jungster Studienergebnisse eine Ubersicht uber die derzeit vorliegenden Therapieempfehlungen bieten. Diese umfasst Blutdruck- und Hirndrucktherapie, hamostaseologische Masnahmen und neurochirurgische Therapieoptionen sowie sekundarprophylaktische Empfehlungen.

Stroke is potentially preventable through risk factor modification. Over the past decade, there has been considerable interest on microalbuminuria as a risk factor for chronic diseases. The concept of microalbuminuria was originally introduced, about 25 years ago, to clinical practice as a useful marker of nephropathy. Since then various studies reported an association of microalbuminuria with the increased risk of cardiovascular events and all cause of mortality in subjects with or without diabetes. The presence of microalbuminuria was related to left ventricular dysfunction, stroke, and myocardial infarction. Microalbuminuria may be a predictor of stroke but further studies are required. However data on prognostic significance and therapeutic consequence, particularly in haemorrhagic stroke are lacking. This review focuses on the importance of microalbuminuria for cerebrovascular disease, stressing the clinical and therapeutic implications using antihypertensive therapy to control the urinary albumin excretion.

Background: We report a treatment option in surgical therapy of locally advanced renal cell carcinoma (RCC). Method: A 63-year-old patient with locally advanced RCC including an atrial thrombus underwent 2 cycles of neoadjuvant therapy (Sutent® 50 mg daily for 4 weeks followed by 2 weeks off) and then tumor surgery. Primary surgical therapy had to be delayed because of suspected bronchial carcinoma and additional diagnostics. After neoadjuvant therapy to downsize the tumor thrombus and exclusion of any additional malignant tumors, operation was done via abdominal access; no sternotomy was necessary. Results: Histopathological examinations of the primary tumor after tyrosine kinase inhibitor therapy were evaluated and compared to tumor biopsy material taken before therapy. Conclusion: Neoadjuvant therapy with Sutent® may represent a favorable treatment option in cases of locally advanced clear-cell RCC with extended tumor thrombus.

Headache classification is a dynamic process through clinical testing and re-testing of current and proposed criteria. After publication of the second edition of the International Classification of Headache Disorders (ICHD-II), need arose for revisions in the classification of medication overuse headache and chronic migraine. These changes made apparent a further need for broader revisions to the standard formulation of diagnostic criteria for the secondary headaches. Currently, the fourth criterion makes impossible the definitive diagnosis of a secondary headache until the underlying cause has resolved or been cured or greatly ameliorated by therapy, at which time the headache may no longer be present. Given that the main purpose of diagnostic criteria is to enable a diagnosis at the onset of a disease in order to guide treatment, this is unhelpful in clinical practice. In the present paper we propose maintaining a standard approach to the secondary headaches using a set of four criteria A, B, C and D, but we construct these so that the requirement for resolution or successful treatment is removed. The proposal for general diagnostic criteria for the secondary headaches will be entered into the internet-based version of the appendix of ICHD-II. During 2009 the Classification Committee will apply the general criteria to all the specific types of secondary headaches. These, and other changes, will be included in a revision of the entire classification entitled ICHD-IIR, expected to be published in 2010. ICHD-IIR will be printed and posted on the website and will be the official classification of the International Headache Society. Unfortunately, it will be necessary to translate ICHD-IIR into the many languages of the world, but the good news is that no major changes to the headache classification are then foreseen for the next 10 years. Until the printing of ICHD-IIR, the printed ICHD-II criteria remain in place for all other purposes. We issue a plea to the headache community to use and study these proposed general criteria for the secondary headaches in order to provide more evidence for their utility—before their incorporation in the main body of the classification.

Die Lebensqualitat nierentransplantierter Patienten ruckt zunehmend in den Mittelpunkt des Interesses. Einen nicht zu unterschatzenden Einfluss haben hierbei auch Fragen der Sexualitat. Ein Grosteil der dialysepflichtigen Patienten leidet unter verschiedenartigsten Storungen der Sexualfunktion, dies betrifft ca. 50% der mannlichen und einen noch groseren Anteil der weiblichen Patienten. Im Vordergrund stehen bei Frauen Libido- und Zyklusstorungen, bei Mannern Erektionsstorungen. Nach erfolgreicher Nierentransplantation erreicht eine Vielzahl der betroffenen Frauen eine Normalisierung der Sexualfunktion wahrend Potenzstorungen bei Mannern haufig persistieren. Hier ist heute aber in vielen Fallen eine effektive medikamentose Therapie moglich. Frauen konnen bei stabiler Transplantatfunktion nach Nierentransplantation unter enger arztlicher Kontrolle eine erfolgreiche Schwangerschaft anstreben.

Aus vielfaltigen physiologischen Veranderungen der Organsysteme resultiert eine Pradisposition zur Entwicklung einzelner Krankheitsbilder in der Schwangerschaft. Dabei spielen Erkrankungen des Harntraktes eine bedeutende Rolle.

A microscopic theory for the nonlinear terahertz response of excited semiconductor systems is presented. It is shown that the measurable quantities in typical terahertz transmission/reflection experiments contain large ponderomotive contributions which mask the signatures from terahertz-induced many-body transitions. A scheme is developed to remove the ponderomotive contributions and applied to isolate the signatures of Rabi oscillations of an exciton population. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

We report the case of a severe acute asthma, which required, after optimal medical therapy, helium and sevoflurane CO-administration after tracheal intubation. The Anesthetic Conserving Device allowed sevoflurane use with intensive care unit's ventilator. The helium-sevoflurane association was maintained during 9 days to decrease the bronchospasm, waiting for the efficiency of an aetiologic treatment. We discuss the suitability of this association to treat severe acute asthma, and its administration modalities.

In end-stage renal disease patients anemia is known to be an independent risk factor for cardiovascular disease and death. In a monocenter retrospective analysis, we investigated 207 stable patients (68 women/139 men) who underwent a first renal transplantation. Immunosuppressive therapy was performed with either cyclosporine plus mycophenolate mofetil, tacrolimus plus mycophenolate mofetil, or rapamycin plus mycophenolate mofetil; 43.5% of the patients were treated with steroids. Seventy-eight patients (37.7%) displayed anemia, including 8.7% with a severe disorder displaying an average hemoglobin (Hb) level of6.8 mmo/L in men and6.2 mmol/L in women. In 8.2% of the cases, we observed moderate anemia (Hb 6.8-7.4 mmol/L in men and 6.2-6.8 mmol/L in women), and in 20.8% (29 men and 14 women), mild anemia (Hb8.06 mmol/L in men and7.45 mmol/L in women). Erythropoietin was administered in 55.5% of patients with severe anemia, 53% with moderate anemia, and 11.6% with mild anemia. Serum creatinine level was a significant predictor of anemia (B -0.004; SE 0.001; P.01). Among patients with creatinine200 micromol/L, 63% were anemic compared with 22% of those with a serum creatinine level200 micromol/L (P.05). No correlation was observed with immunosuppressive medication or treatment with angiotensin-converting enzyme inhibitors/angiotensin-II receptor antagonists. During a 3-year follow-up, both mortality and graft failure rates were significantly greater among anemic patients nonanemic patients (mortality 3.3% vs 0.5%, P.001; graft failure 4.3% vs 0%, P.001). We found an unexpectedly high incidence of anemia in patients with well-functioning grafts. Anemia as a risk factor for mortality and graft failure should be treated more intensively among renal transplant patients.

Molekularbiologische Tumormarker und Prognoseparameter sind Voraussetzung fur eine differenzierte Diagnostik und daraus resultierend fur eine individuelle Prognosebewertung und Therapiewahl auch fur Patienten mit Nierenzelltumoren (NZK). Es ist heute moglich, Tumoren sehr komplex unter Einsatz von Hochdurchsatzverfahren zu charakterisieren. Durch genetische Analysen konnten die einzelnen histopathologisch definierten Subtypen der Nierenzelltumoren als eigenstandige Tumorentitaten definiert werden. Die genetischen Merkmale der einzelnen Subtypen konnen heute zur Diagnosesicherung am Tumormaterial, aber auch an der Biopsie eingesetzt werden. Daruber hinaus ist es moglich, metastasierungsspezifische molekulare Muster zu definieren, die zukunftig die Bewertung des Metastasierungspotenzials bereits am Primartumor erlauben. Durch Proteomanalysen im Serum wurden spezifische Proteinmuster im Serum definiert und daraus ableitend erste Kandidatenproteine, die als Biomarker dienen konnten, identifiziert. Hierzu zahlt das SAA-1, welches bei Patienten mit klarzelligen Nierenzellkarzinomen erhoht vorliegt. Da neue Therapeutika fur Patienten mit metastasierten NZK zur Verfugung stehen, ist es notwendig, Patienten fur die effektivste Therapie zu selektieren und fruhzeitig das Therapieversagen zu erkennen. Es konnten Biomarker im Tumorgewebe und im Serum identifiziert werden, die mit dem Therapieansprechen korrelieren.

BACKGROUND BK virus nephropathy has an increasing role in renal transplant dysfunction, since new, highly potent immunosuppressive drugs have been introduced into therapy following renal transplantation. Diagnosis of acute impairment of renal transplant function is complicated by difficulty in differentiating BK virus nephropathy from acute rejection. PATIENTS AND METHODS We retrospectively described the findings and therapeutic approaches of 6 consecutive patients with BK virus nephropathy in our transplantation center (75 - 80 transplantations/ year). BK virus nephropathy was classified according to Drachenberg et al. [2004]. RESULTS We observed an incidence rate of < 1% for BK nephropathy in our center. Four patients had a pattern B whereas 2 patients revealed a pattern C of BK virus nephropathy. Focal C4d-positive staining of peritubular capillaries were found in 2 of the 6 cases. For earlier detection of BK nephropathy, a diagnostic algorithm for each patient after renal transplantation was established. Urine was continuously monitored by cytology for decoy cells and PCR for BK virus DNA. If PCR was also positive for the BK virus in plasma, biopsy of the renal allograft was performed. Thereby diagnosis could be confirmed sooner. For treatment of BK nephropathy in our center, we reduced immunosuppressive agents and initiated a virustatic treatment with cidofovir in the first 3 cases. However, results were not satisfactory and two allografts were lost. We then reconsidered our therapeutic approach and switched the immunosuppressive treatment to leflunomide with consistent low dose steroids. We use therapeutic drug monitoring for leflunomide and aim at a target level of 40 - 100 microg/ml. We lost no allograft with BK nephropathy since using this therapeutic approach. CONCLUSION In our center, leflunomide therapy, but not cidofovir, was effective in patients with BK virus nephropathy of the renal allograft.