The combination of chemotherapy with the vascular endothelial growth factor (VEGF) antibody bevacizumab is a standard of care in advanced colorectal cancer (CRC). However, biomarkers predicting ...outcome of bevacizumab-containing treatment are lacking. As angiopoietin-2 (Ang-2) is a key regulator of vascular remodelling in concert with VEGF, we investigated its role as a biomarker in metastatic CRC.
Serum Ang-2 levels were measured in 33 healthy volunteers and 90 patients with CRC. Of these, 34 had metastatic disease and received bevacizumab-containing therapy. To determine the tissue of origin of Ang-2, quantitative real-time PCR was performed on microdissected cryosections of human CRC and in a murine xenograft model of CRC using species-specific amplification.
Ang-2 originated from the stromal compartment of CRC tissues. Serum Ang-2 levels were significantly elevated in patients with metastatic CRC compared with healthy controls. Amongst patients receiving bevacizumab-containing treatment, low pre-therapeutic serum Ang-2 levels were associated with a significant better response rate (82 vs 31%; P<0.01), a prolonged median progression-free survival (14.1 vs 8.5 months; P<0.01) and a reduction of 91% in the hazard of death (P<0.05).
Serum Ang-2 is a candidate biomarker for outcome of patients with metastatic CRC treated with bevacizumab-containing therapy, and it should be further validated to customise combined chemotherapeutic and anti-angiogenic treatment.
Most reinforcement learning algorithms optimize the expected return of a Markov Decision Problem. Practice has taught us the lesson that this criterion is not always the most suitable because many ...applications require robust control strategies which also take into account the variance of the return. Classical control literature provides several techniques to deal with risk-sensitive optimization goals like the so-called worst-case optimality criterion exclusively focusing on risk-avoiding policies or classical risk-sensitive control, which transforms the returns by exponential utility functions. While the first approach is typically too restrictive, the latter suffers from the absence of an obvious way to design a corresponding model-free reinforcement learning algorithm. Our risk-sensitive reinforcement learning algorithm is based on a very different philosophy. Instead of transforming the return of the process, we transform the temporal differences during learning. While our approach reflects important properties of the classical exponential utility framework, we avoid its serious drawbacks for learning. Based on an extended set of optimality equations we are able to formulate risk-sensitive versions of various well-known reinforcement learning algorithms which converge with probability one under the usual conditions.PUBLICATION ABSTRACT
Abstract
Introduction
Super-refractory status epilepticus (SRSE) represents the culmination of refractory status epilepticus (RSE) and carries a significant risk of poor neurological outcome and high ...mortality. RSE is not defined primarily by seizure duration, but by failure to respond to appropriate antiseizure treatment. SRSE is present when a RSE persists or recurs after more than 24 h of treatment with anesthetics. No evidence-based treatment algorithms can be provided for SRSE. Therefore, we propose a pragmatic standard operating procedure (SOP) for the management of SRSE that addresses the existing uncertainties in the treatment of SRSE and provides options for resolution and decision-making.
Comments
First, we recommend the assessment of persistent seizure activity and the evaluation of differential diagnoses to confirm correct diagnosis. Relevant differential diagnoses include psychogenic non-epileptic seizures, hypoxic, metabolic, or toxic encephalopathies, and tetanus. During SE or in severe encephalopathies, a so-called electroclinical ictal-interictal continuum may occur, which denotes an intermediate stage that cannot be defined with certainty as ictal or interictal by EEG and should not lead to harmful overtreatment. Because both prognosis and specific treatment options depend crucially on the etiology of SRSE, the etiological evaluation should be performed rapidly. When SRSE is confirmed, various pharmacological and non-pharmacological treatment options are available.
Conclusion
We provide a pragmatical SOP for adult people with SRSE.
Post-COVID-19 encephalomyelitis Kim, Ji-Won; Abdullayev, Nuran; Neuneier, Janina ...
Neurological research and practice,
03/2021, Letnik:
3, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Since the outbreak of coronavirus disease 2019 (COVID-19), a growing number of cases of acute transverse myelitis associated with COVID-19 have been reported. Here, we present the case of a patient ...who developed sensory ataxia after COVID-19 with MR lesions suggestive for longitudinal myelitis and in the splenium of the corpus callosum. The patient was successfully treated with immunoadsorption.
Meningitis and spinal infections with Gram-negative bacteria after local injections for treatment of chronic back pain are rare. This study investigated an outbreak of Pseudomonas aeruginosa ...infections following computed tomography (CT)-guided spinal injections (SI).
A case was defined as a spinal infection or meningitis with P. aeruginosa after SI between 10th January and 1st March 2019 in the same outpatient clinic. Patients without microbiological evidence of P. aeruginosa but with a favourable response to antimicrobial therapy active against P. aeruginosa were defined as probable cases.
Twenty-eight of 297 patients receiving CT-guided SI during the study period developed meningitis or spinal infections. Medical records were available for 19 patients. In 15 patients, there was microbiological evidence of P. aeruginosa, and four patients were defined as probable cases. Two of 19 patients developed meningitis, while the remaining 17 patients developed spinal infections. The median time from SI to hospital admission was 8 days (interquartile range 2–23 days). Patients mainly presented with back pain (N=18; 95%), and rarely developed fever (N=3; 16%). Most patients required surgery (N=16; 84%). Seven patients (37%) relapsed and one patient died. Although the source of infection was not identified microbiologically, documented failures in asepsis when performing SI probably contributed to these infections.
SI is generally considered safe, but non-adherence to asepsis can lead to deleterious effects. Spinal infections caused by P. aeruginosa are difficult to treat and have a high relapse rate.
Narcolepsy is a hypersomnolence disorder of central origin that presents with a disturbance of the wake-sleep regulation. Lead symptoms consist of excessive daytime sleepiness and cataplexy. ...Nowadays, two types of narcolepsy are distinguished. Type 1 narcolepsy, formerly known as narcolepsy with cataplexy, is based on hypocretin deficiency. The cause of type 2 narcolepsy, formerly known as narcolepsy without cataplexy, remains mainly unknown. A multimodal approach is necessary for diagnosis. The mean latency between the onset of disease and diagnosis in Europe ranges 14 years. Narcolepsy has a major impact on workability and quality of life. The management of narcolepsy is usually life-long and includes non-pharmacological approaches and a symptomatic pharmacological treatment.
Differentiating brain tumors from nonneoplastic lesions using conventional MRI may be challenging. Clinical symptoms often remain unspecific, and imaging findings from MRI may be inconclusive. We ...present the case of a 23-year-old woman in whom an MRI suggested a cerebral venous sinus thrombosis. On the other hand, additional atypical MRI findings raised doubts regarding the initial diagnosis. Given the need for a diagnostic procedure with higher sensitivity and specificity for neoplastic tissue, PET with the radiolabeled somatostatin receptor ligand DOTATATE ( 68 Ga-DOTA- d -Phe1-Tyr3-octreotate) was performed. DOTATATE PET facilitated the diagnosis of a falcine meningioma consistent with its value for the differential diagnosis of meningioma.
Tie2-expressing monocytes (TEM) promote tumor angiogenesis and growth in experimental cancer models. The role of TEM in cancer patients is unknown. We studied TEM in healthy volunteers and colorectal ...cancer (CRC) patients. Although TEM were detectable in the blood and tumor lesions of CRC patients, their frequency and functional phenotype showed no correlation with levels of angiopoietin-2 or vascular endothelial growth factor, microvessel density, tumor markers, tumor stage, or outcome of antiangiogenic therapy. These unexpected findings are at odds with murine tumor models and question the diagnostic or therapeutic value of TEM in human cancer.
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