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  • 1
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    Treatment of established status epilepticus in the elderly - a study protocol for a prospective multicenter double-blind comparative effectiveness trial (ToSEE)
    Springer Science and Business Media LLC ; 2020
    In:  BMC Neurology Vol. 20, No. 1 ( 2020-12)
    Details
    In: BMC Neurology, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2020-12)
    Abstract: Status epilepticus (SE) is a common neurological emergency condition that especially affects the elderly and old population. Older people with SE frequently have non-convulsive SE (NCSE) and are also at special risk of suffering a poor outcome. The application of benzodiazepines fails to control SE in about one third of the cases. For benzodiazepine refractory SE (BRSE) in elderly, there is little evidence that would justify the choice of one of the commonly used antiepileptic drugs. The present study aims to generate evidence for the treatment of BRSE in this age group. Methods We will conduct a prospective, randomized, double-blind comparative effectiveness study in more than twenty hospitals in Germany over a four-year period. Four hundred and seventy-seven elderly patients (≥ 65 years old) diagnosed with BRSE will be allocated by 1:1 randomization to receive either levetiracetam or valproate. All types of SE will be considered. For the diagnosis NCSE a verification by EEG is required. Levetiracetam or valproate will be administered in one single infusion. The primary endpoint is the stable cessation of ictal activity 15 min after the start of infusion persisting for the following 45 min of observation. EEG recording is maintained over the whole observation period, clinical examinations are conducted in predefined intervals. In case of treatment success patients and study staff remain blinded until 60 min after the start of the infusion. Adverse events will be recorded until the end of the study. EEG data will be reviewed by two external independent experts. To obtain data about the further treatment of SE, intrahospital complications and the functional outcome in the short term the study participants will be observed until the day of discharge or day 30 whichever is earliest. Discussion ToSEE is the first study which shall deliver evidence for the SE-therapy in the elderly and old population in a controlled prospective comparator study. By design it also shall collect information about therapy regimes and outcome aspects of this disease. Trial registration The trial has been registered at the German Clinical Trials Register on 3 July, 2020 ( DRKS00022308 ,  https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML & TRIAL_ID=DRKS00022308 ).
    Type of Medium: Online Resource
    ISSN: 1471-2377
    URL: Article
    DOI: 10.1186/s12883-020-02001-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2041347-6
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  • 2
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    STAT3 controls matrix metalloproteinase-1 expression in colon carcinoma cells by both direct and AP-1-mediated interaction with the MMP-1 promoter
    Walter de Gruyter GmbH ; 2011
    In:  Biological Chemistry Vol. 392, No. 5 ( 2011-05-01)
    Details
    In: Biological Chemistry, Walter de Gruyter GmbH, Vol. 392, No. 5 ( 2011-05-01)
    Abstract: Aberrant activation of STAT3 in colorectal carcinoma (CRC) tissue is correlated with elevated expression of matrix metalloproteinase-1 (MMP-1). We analyzed transcriptional regulation of the human MMP-1 promoter in CRC cells by tyrosine phosphorylated (pY-) STAT3. One of six putative STAT binding elements within a 4.3 kb MMP-1 trancriptional promoter fragment showed a particular high affinity for STAT3 in vitro . However, the most profound regulatory influence on MMP-1 promoter activity resides in a proximal region relative to the transcriptional start, bearing a pair of putative binding sites for STAT3 and AP-1. Mutational analysis of the combined STAT3/AP-1 recognition element revealed that the integrity of the STAT3 binding site is necessary, but not sufficient for both DNA interaction and transcriptional regulation by activated STAT3. Instead, the adjacent AP-1 site was essential for pY-STAT3-mediated transcription on the MMP-1 promoter. DNA-protein binding assays provided strong evidence for complex formation of STAT3 and c-Jun governed by protein-protein contacts. We observed striking coincidence for concerted aberrant activation of both STAT3 and AP-1 in human colon cancer specimens. This finding supports the notion that the combination of inappropriate STAT3 and AP-1 activities drives elevated MMP-1 expression and tissue invasion in colorectal cancer and is of clinical relevance.
    Type of Medium: Online Resource
    ISSN: 1437-4315 , 1431-6730
    URL: Article
    DOI: 10.1515/bc.2011.038
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2011
    detail.hit.zdb_id: 1466062-3
    SSG: 12
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  • 3
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    Pharmacotherapy and intensive care aspects of status epilepticus: update 2020/2021
    Springer Science and Business Media LLC ; 2021
    In:  Der Anaesthesist Vol. 70, No. 10 ( 2021-10), p. 874-887
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    In: Der Anaesthesist, Springer Science and Business Media LLC, Vol. 70, No. 10 ( 2021-10), p. 874-887
    Abstract: Focused treatment of epileptic emergencies, and in particular status epilepticus (SE), require a reliable differentiation of epileptic syndromes. In these cases, and especially in cases with predominant non-motor symptoms, clinical and electroencephalographic expertise is necessary. In 2020 the German guidelines for the management of SE were updated, which adhere to a strict stage-based treatment algorithm. The staged approach includes the administration of benzodiazepines, antiepileptic drugs and anesthetic agents. So far, efforts failed to determine the most effective and safest antiepileptic drug without interaction potential. Therefore, for the differentiated treatment of SE, individual pre-existing medical conditions and concomitant circumstances must be considered, added by the experience of the medical team. Therapeutic interventions especially for refractory forms of SE have been shown to be complex with relevant implications concerning intensive care aspects. Consequently, the modern treatment strategy of SE is characterized by an interdisciplinary approach. Future research is needed to define the optimal treatment of non-convulsive SE, in particular regarding the time point and degree of treatment escalation with associated ethical considerations.
    Type of Medium: Online Resource
    ISSN: 0003-2417 , 1432-055X
    URL: Article
    DOI: 10.1007/s00101-021-01000-y
    RVK:
    XA 22100
    Language: German
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 3122926-8
    detail.hit.zdb_id: 1458421-9
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  • 4
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    Metabolic Long-Term Monitoring of Transcorneal Electrical Stimulation in Retinitis Pigmentosa
    S. Karger AG ; 2022
    In:  Ophthalmic Research Vol. 65, No. 1 ( 2022), p. 52-59
    Details
    In: Ophthalmic Research, S. Karger AG, Vol. 65, No. 1 ( 2022), p. 52-59
    Abstract: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 Transcorneal electrical stimulation (TES) is a new therapeutical approach for retinitis pigmentosa (RP). With progression of RP, degeneration of photoreceptors results in lower oxygen consumption of the retina. Retinal oximetry (RO) is a noninvasive method to analyze oxygen saturation in retinal vessels and has shown promising short-term results as a therapy monitoring tool for TES. The aim of our study was to measure the long-term effects of TES on RO parameters over a period of 3 years (3Y). 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 A total of 18 eyes of 9 subjects (5♀ 4♂) suffering from RP were examined at baseline (BL), 6 months, and 3Y of TES (OkuStim®) treatment. TES was performed for 30 min once a week at 200% of the individual phosphene threshold simultaneously on both eyes. The oxygen saturation was examined at BL and following TES therapy with the oxygen saturation tool of the Retinal Vessel Analyser (IMEDOS Systems UG, Jena, Germany). The global oxygen saturation parameters (in %), within 1.0–1.5 optic-disc diameters from the disc margin, in retinal arterioles (A-SO 〈 sub 〉 2 〈 /sub 〉 ) and venules (V SO 〈 sub 〉 2 〈 /sub 〉 ) were measured and their difference (A-V SO 〈 sub 〉 2 〈 /sub 〉 ) was calculated. In addition, we recorded the diameters in the main arterioles (D-A) and venules (D-V). ANOVA-based linear mixed-effects models were employed for statistical analysis using SPSS®. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 After 3Y of TES treatment both the mean A-SO 〈 sub 〉 2 〈 /sub 〉 (from 96.35 ± 12.76% to 100.89 ± 5.87%, 〈 i 〉 p 〈 /i 〉 = 0.22) and V SO 〈 sub 〉 2 〈 /sub 〉 (from 62.20 ± 11.55% to 64.55 ± 8.24%, 〈 i 〉 p 〈 /i 〉 = 0.77) increased slightly. The A-V SO 〈 sub 〉 2 〈 /sub 〉 , which corresponds to the oxygen consumption of the retina, presented also with a slight increment from 34.15 ± 9.68% at BL to 36.23 ± 7.71% without reaching statistical significance ( 〈 i 〉 p 〈 /i 〉 = 0.27). TES also did not appear to alter the vascular diameter parameters, D-A and D-V ( 〈 i 〉 p 〈 /i 〉 & #x3e; 0.05). 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Our long-term observations indicate that TES therapy in RP might lead to a slight increment in oxygen consumption of the retina. However, a larger cohort and longer duration may be needed to adequately power a follow-up study and to confirm this trend reflecting a possible benefit of TES for RP.
    Type of Medium: Online Resource
    ISSN: 0030-3747 , 1423-0259
    URL: Article
    DOI: 10.1159/000519998
    RVK:
    XA 10000
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2022
    detail.hit.zdb_id: 1483177-6
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  • 5
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    Prognosis and management of acute symptomatic seizures: a prospective, multicenter, observational study
    Springer Science and Business Media LLC ; 2023
    In:  Annals of Intensive Care Vol. 13, No. 1 ( 2023-09-15)
    Details
    In: Annals of Intensive Care, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2023-09-15)
    Abstract: Acute symptomatic epileptic seizures are frequently seen in neurocritical care. To prevent subsequent unprovoked seizures, long-term treatments with antiseizure medications are often initiated although supporting evidence is lacking. This study aimed at prospectively assessing the risk of unprovoked seizure relapse with respect to the use of antiseizure medications. It was hypothesized that after a first acute symptomatic seizure of structural etiology, the cumulative 12-month risk of unprovoked seizure relapse is ≤ 25%. Methods Inclusion criteria were age ≥ 18 and acute symptomatic first-ever epileptic seizure; patients with status epilepticus were excluded. Using telephone and mail interviews, participants were followed for 12 months after the acute symptomatic first seizure. Primary endpoint was the occurrence and timing of a first unprovoked seizure relapse. In addition, neuro-intensivists in Germany were interviewed about their antiseizure treatment strategies through an anonymous online survey. Results Eleven of 122 participants with structural etiology had an unprovoked seizure relapse, resulting in a cumulative 12-month risk of 10.7% (95%CI, 4.7%–16.7%). None of 19 participants with a non-structural etiology had a subsequent unprovoked seizure. Compared to structural etiology alone, combined infectious and structural etiology was independently associated with unprovoked seizure relapse (OR 11.1; 95%CI, 1.8–69.7). Median duration of antiseizure treatment was 3.4 months (IQR 0–9.3). Seven out of 11 participants had their unprovoked seizure relapse while taking antiseizure medication; longer treatment durations were not associated with decreased risk of unprovoked seizure relapse. Following the non-representative online survey, most neuro-intensivists consider 3 months or less of antiseizure medication to be adequate. Conclusions Even in case of structural etiology, acute symptomatic seizures bear a low risk of subsequent unprovoked seizures. There is still no evidence favoring long-term treatments with antiseizure medications. Hence, individual constellations with an increased risk of unprovoked seizure relapse should be identified, such as central nervous system infections causing structural brain damage. However, in the absence of high-risk features, antiseizure medications should be discontinued early to avoid overtreatment.
    Type of Medium: Online Resource
    ISSN: 2110-5820
    URL: Article
    DOI: 10.1186/s13613-023-01183-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2617094-2
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  • 6
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    IGF2BP1 is a targetable SRC/MAPK-dependent driver of invasive growth in ovarian cancer
    Informa UK Limited ; 2021
    In:  RNA Biology Vol. 18, No. 3 ( 2021-03-04), p. 391-403
    Details
    In: RNA Biology, Informa UK Limited, Vol. 18, No. 3 ( 2021-03-04), p. 391-403
    Type of Medium: Online Resource
    ISSN: 1547-6286 , 1555-8584
    URL: Article
    DOI: 10.1080/15476286.2020.1812894
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2159587-2
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  • 7
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    Optical coherence tomography angiography findings in transcorneal electrical stimulation in retinitis pigmentosa
    Wiley ; 2021
    In:  Acta Ophthalmologica Vol. 99, No. S265 ( 2021-01)
    Details
    In: Acta Ophthalmologica, Wiley, Vol. 99, No. S265 ( 2021-01)
    Abstract: Transcorneal electrical stimulation (TES) is a novel treatment approach for patients with retinitis pigmentosa (RP). The aim of our study was to observe changes in optical coherence tomography angiography (OCTA) that would be attributed to TES treatment. Methods A total of 43 eyes of 22 subjects (11♀ 11♂) suffering from RP were examined at baseline (BL), after first stimulation (TS), 1 week after first stimulation (1W) and six months (6M) after treatment initiation. TES was performed simultaneously on both eyes for 30 minutes weekly. 9 × 15 mm OCTA scans were recorded with a PLEX Elite 9000 swept‐source OCTA device (Carl Zeiss Meditec AG, Jena). Vascular density metrics as perfusion density (PD) and vessel density (VD) were calculated automatically for the macular area by using standardized ETDRS grids. In addition, the capillary perfusion density (CPD) and the capillary flux index (CFI) of the peripapillary nerve fibre layer microvasculature in all four quadrants of an annulus centred at the optic disc were measured. All parameters were determined over all retinal layers and separately for the superficial (SCP) and deep capillary plexus (DCP). ANOVA‐based linear mixed‐effects models were calculated with SPSS®. Results Throughout the course of TES treatment, the macular VD and PD of all retinal layers in all subsections showed a slight decrement without reaching statistical significance (p  〉  0.05), also when analysed separately in the SCP (p  〉  0.06) and DCP (p  〉  0.11). In analogy, the average CPD and CFI also presented with a slight decrement (p  〉  0.19). When analysed in subsections, the temporal macular subsections showed significantly lower VD and PD values when compared to the other subsections of the ETDRS grid. Conclusions Our preliminary data with SS‐OCTA indicate that vascular density metrics in the macular region and the peripapillary microvasculature remain unaffected despite ongoing TES treatment.
    Type of Medium: Online Resource
    ISSN: 1755-375X , 1755-3768
    URL: Issue
    URL: Article
    DOI: 10.1111/aos.v99.s265
    DOI: 10.1111/j.1755-3768.2020.0163
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2466981-7
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  • 8
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    Optical coherence tomography angiography findings in patients undergoing transcorneal electrical stimulation for treating retinitis pigmentosa
    Springer Science and Business Media LLC ; 2021
    In:  Graefe's Archive for Clinical and Experimental Ophthalmology Vol. 259, No. 5 ( 2021-05), p. 1167-1177
    Details
    In: Graefe's Archive for Clinical and Experimental Ophthalmology, Springer Science and Business Media LLC, Vol. 259, No. 5 ( 2021-05), p. 1167-1177
    Abstract: Transcorneal electrical stimulation (TES) is a novel treatment approach for patients with retinitis pigmentosa (RP). The aim of our study was to observe changes in optical coherence tomography angiography (OCTA) that would be attributed to TES treatment. Methods A total of 73 eyes were included: 43 eyes of 22 subjects (11 ♀, 11 ♂) suffering from RP were examined at baseline (BL), after first stimulation (TS), 1 week (1W), and 6 months (6M) after treatment initiation and were compared with 30 control eyes of 15 subjects (8 ♀, 7 ♂). TES was performed simultaneously on both eyes for 30 min weekly. OCTA scans of 9 × 15 mm were recorded with a PLEX Elite 9000 swept-source OCTA device (Carl Zeiss Meditec AG, Jena). Vascular density metrics such as perfusion density (PD) and vessel density (VD) were calculated automatically for the macular area by using standardised extended early treatment diabetic retinopathy study (ETDRS) grids centred around the fovea. In addition, the capillary perfusion density (CPD) and the capillary flux index (CFI) of the peripapillary nerve fibre layer microvasculature in all four quadrants of an annulus centred at the optic disc were measured. All parameters were determined over all retinal layers and separately for the superficial (SCP) and deep capillary plexus (DCP). ANOVA-based linear mixed-effects models were calculated with SPSS®. Results Throughout the course of TES treatment, the macular VD and PD of all retinal layers in all subsections showed a slight decrement without reaching statistical significance, also when analysed separately in the SCP and DCP ( p   〉  0.08). In analogy, the average CPD and CFI also presented with a slight decrement ( p   〉  0.20). However, when compared with controls, most OCTA parameters showed a significant decrement ( p   〈  0.05). When analysed systematically in all subsections of the extended ETDRS grid, the temporal macular subsections within the outer ring (radius 1.5–3 mm) and also of the peripheral C1, C2, and C3 rings (radius 3–7.5 mm) showed lower VD and PD values when compared with the other subsections ( p   〈  0.05). Conclusion Vascular density metrics in the macular region and the peripapillary microvasculature appear to remain unaffected by continuous TES treatment within a period of 6 months.
    Type of Medium: Online Resource
    ISSN: 0721-832X , 1435-702X
    URL: Article
    DOI: 10.1007/s00417-020-04963-7
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1459159-5
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  • 9
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    Study protocol: register on the prognosis of acute symptomatic seizures (PROSA register)—A prospective multicenter observational study
    Springer Science and Business Media LLC ; 2021
    In:  Zeitschrift für Epileptologie Vol. 34, No. 4 ( 2021-11), p. 349-354
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    In: Zeitschrift für Epileptologie, Springer Science and Business Media LLC, Vol. 34, No. 4 ( 2021-11), p. 349-354
    Abstract: Acute symptomatic epileptic seizures occur in close temporal relation to an acute disturbance of brain function. They are associated with a low risk of subsequent unprovoked seizures; thus, current guidelines recommend not to administer a long-term antiseizure medication; however, in clinical practice long-term secondary seizure prophylaxis is frequently initiated. The seizure prognosis after guideline-conform untreated or only briefly treated acute symptomatic seizures, is so far unknown. Hypothesis Following an acute symptomatic first epileptic seizure of structural etiology, the 1‑year risk of subsequent unprovoked seizures is not higher than 25%, even if antiseizure medication was not applied or for a short period only. Methods The PROSE register is a single-arm, open, prospective, multicenter observational study. A total of 115 subjects aged 18 years or older with an acute symptomatic first epileptic seizure of structural etiology will be included if the seizure was not a status epilepticus. Intrahospital follow-up will be based on the hospital records. Telephone follow-up interviews will be conducted 3, 6, and 12 months after the acute symptomatic seizure. Discussion The PROSE register will shed light on current treatment practice of acute symptomatic seizures and the actual seizure outcome within 1 year. The results are assumed to support the current evidence that giving antiseizure medication for a longer period of time exceeding the acute phase of the underlying condition is unnecessary. Trial registration The study was prospectively registered in the German Clinical Trials Register under the ID DRKS00017811.
    Type of Medium: Online Resource
    ISSN: 1617-6782 , 1610-0646
    URL: Article
    DOI: 10.1007/s10309-021-00444-x
    Language: German
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 3154797-7
    detail.hit.zdb_id: 2105600-6
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  • 10
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    Phenobarbital in super‐refractory status epilepticus ( PIRATE ): A retrospective, multicenter analysis
    Wiley ; 2023
    In:  Epilepsia Vol. 64, No. 6 ( 2023-06), p. 1482-1492
    Details
    In: Epilepsia, Wiley, Vol. 64, No. 6 ( 2023-06), p. 1482-1492
    Abstract: Super‐refractory status epilepticus (SRSE) is an enduring or recurring SE after 24 h or more of general anesthesia. This study aimed to evaluate the efficacy and safety of phenobarbital (PB) for the treatment of SRSE. Methods This retrospective, multicenter study included neurointensive care unit (NICU) patients with SRSE treated with PB between September 2015 and September 2020 from six participating centers of the Initiative of German NeuroIntensive Trial Engagement (IGNITE) to evaluate the efficacy and safety of PB treatment for SRSE. The primary outcome measure was seizure termination. In addition, we evaluated maximum reached serum levels, treatment duration, and clinical complications using a multivariate generalized linear model. Results Ninety‐one patients were included (45.1% female). Seizure termination was achieved in 54 patients (59.3%). Increasing serum levels of PB were associated with successful seizure control (per μg/mL: adjusted odds ratio [adj.OR] = 1.1, 95% confidence interval [CI] 1.0–1.2, p   〈  .01). The median length of treatment in the NICU was 33.7 [23.2–56.6] days across groups. Clinical complications occurred in 89% ( n  = 81) of patients and included ICU‐acquired infections, hypotension requiring catecholamine therapy, and anaphylactic shock. There was no association between clinical complications and treatment outcome or in‐hospital mortality. The overall average modified Rankin scale (mRS) at discharge from the NICU was 5 ± 1. Six patients (6.6%) reached mRS ≤3, of whom five were successfully treated with PB. In‐hospital mortality was significantly higher in patients in whom seizure control could not be achieved. Significance We observed a high rate in attainment of seizure control in patients treated with PB. Success of treatment correlated with higher dosing and serum levels. However, as one would expect in a cohort of critically ill patients with prolonged NICU treatment, the rate of favorable clinical outcome at discharge from the NICU remained extremely low. Further prospective studies evaluating long‐term clinical outcome of PB treatment as well as an earlier use of PB at higher doses would be of value.
    Type of Medium: Online Resource
    ISSN: 0013-9580 , 1528-1167
    URL: Article
    DOI: 10.1111/epi.17608
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2002194-X
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