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- Menchon, JM, et al.
(author)
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A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder
- 2021
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In: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:4, s. 1234-1247
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Journal article (peer-reviewed)abstract
- Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule. Safety, efficacy, and functionality assessments were performed at 3, 6, and 12 months post implant. An independent Clinical Events Committee classified and coded all adverse events (AEs) according to EN ISO14155:2011. All patients experienced AEs (195 in total), with the majority of these being mild (52% of all AEs) or moderate (37%). Median time to resolution was 22 days for all AEs and the etiology with the highest AE incidence was ‘programming/stimulation’ (in 26 patients), followed by ‘New illness, injury, condition’ (13 patients) and ‘pre-existing condition, worsening or exacerbation’ (11 patients). Sixteen patients reported a total of 36 serious AEs (eight of them in one single patient), mainly transient anxiety and affective symptoms worsening (20 SAEs). Regarding efficacy measures, Y-BOCS reduction was 42% at 12 months and the responder rate was 60%. Improvements in GAF, CGI, and EuroQol-5D index scores were also observed. In sum, although some severe AEs occurred, most AEs were mild or moderate, transient and related to programming/stimulation and tended to resolve by adjustment of stimulation. In a severely treatment-resistant population, this open-label study supports that the potential benefits outweigh the potential risks of DBS.
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- Chalupsky, J., et al.
(author)
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Characteristics of focused soft X-ray free-electron laser beam determined by ablation of organic molecular solids
- 2007
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In: Optics Express. - 1094-4087. ; 15:10, s. 6036-6043
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Journal article (peer-reviewed)abstract
- A linear accelerator based source of coherent radiation, FLASH (Free-electron LASer in Hamburg) provides ultra-intense femtosecond radiation pulses at wavelengths from the extreme ultraviolet (XUV; lambda< 100nm) to the soft X-ray (SXR; lambda<30nm) spectral regions. 25-fs pulses of 32-nm FLASH radiation were used to determine the ablation parameters of PMMA - poly ( methyl methacrylate). Under these irradiation conditions the attenuation length and ablation threshold were found to be (56.9 +/- 7.5) nm and similar to 2 mJ center dot cm(-2), respectively. For a second wavelength of 21.7 nm, the PMMA ablation was utilized to image the transverse intensity distribution within the focused beam at mu m resolution by a method developed here.
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- Tronnier, Volker M., et al.
(author)
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The appropriate management of persisting pain after spine surgery : a European panel study with recommendations based on the RAND/UCLA method
- 2019
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In: European spine journal. - : Springer. - 0940-6719 .- 1432-0932. ; 28:1, s. 31-45
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Journal article (peer-reviewed)abstract
- Purpose: Management of patients with persisting pain after spine surgery (PPSS) shows significant variability, and there is limited evidence from clinical studies to support treatment choice in daily practice. This study aimed to develop patient-specific recommendations on the management of PPSS.Methods: Using the RAND/UCLA appropriateness method (RUAM), an international panel of 6 neurosurgeons, 6 pain specialists, and 6 orthopaedic surgeons assessed the appropriateness of 4 treatment options (conservative, minimally invasive, neurostimulation, and re-operation) for 210 clinical scenarios. These scenarios were unique combinations of patient characteristics considered relevant to treatment choice. Appropriateness had to be expressed on a 9-point scale (1 = extremely inappropriate, 9 = extremely appropriate). A treatment was considered appropriate if the median score was ≥ 7 in the absence of disagreement (≥ 1/3 of ratings in each of the opposite sections 1–3 and 7–9).Results: Appropriateness outcomes showed clear and specific patterns. In 48% of the scenarios, exclusively one of the 4 treatments was appropriate. Conservative treatment was usually considered appropriate for patients without clear anatomic abnormalities and for those with new pain differing from the original symptoms. Neurostimulation was considered appropriate in the case of (predominant) neuropathic leg pain in the absence of conditions that may require surgical intervention. Re-operation could be considered for patients with recurrent disc, spinal/foraminal stenosis, or spinal instability.Conclusions: Using the RUAM, an international multidisciplinary panel established criteria for appropriate treatment choice in patients with PPSS. These may be helpful to educate physicians and to improve consistency and quality of care.
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- Mitteldorf, C., et al.
(author)
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Galectin-3 Expression in Primary Cutaneous CD30-Positive Lymphoproliferative Disorders and Transformed Mycosis Fungoides
- 2015
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In: Dermatology. - : S. Karger AG. - 1018-8665 .- 1421-9832. ; 231:2, s. 164-170
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Journal article (peer-reviewed)abstract
- Background: In nodal anaplastic large cell lymphoma, strong expression of galectin-3 (Gal-3) has been found, but only very few cases of primary cutaneous lymphoma have so far been examined. Objectives: To investigate 11 primary cutaneous anaplastic large cell lymphomas (PCALCL), 47 lymphomatoid papuloses (LYP) and 14 cases of transformed mycosis fungoides with CD30 expression (MF-T) for Gal-3 expression. Methods: A Gal-3 score was applied using a photo-based morphometric evaluation program. Double staining for CD30 and Gal-3 was performed. Furthermore, we recorded the cellular and extracellular sublocalization of the signal. Results: The Gal-3 expression in CD30+ tumor cells was significantly lower in MF-T in contrast to CD30+ lymphoproliferative disorders (CD30 LPD; p < 0.001), but we found no differences between PCALCL and LYP (p = 0.42). In PCALCL Gal-3 was more often localized in the cytoplasm in contrast to LYP, in which an equal distribution in the cytoplasm and the nucleus was more common (p = 0.9). Conclusions: The lower Gal-3 expression in MF-T in comparison to CD30 LPD might be an additional criterion to differentiate both entities. The different sublocalization of the Gal-3 signal might reflect a different biological function and behavior. © 2015 S. Karger AG, Basel.
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- Mitteldorf, C., et al.
(author)
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PD-1 and PD-L1 in neoplastic cells and the tumor microenvironment of Merkel cell carcinoma
- 2017
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In: Journal of cutaneous pathology. - : Blackwell Publishing Ltd. - 0303-6987 .- 1600-0560. ; 44:9, s. 740-746
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Journal article (peer-reviewed)abstract
- Background: Merkel cell carcinoma (MCC) is an aggressive neoplasm, which is often associated with Merkel cell polyomavirus (MCPyV). Programmed death-1 (PD-1) and its ligand PD-L1 are key players of the tumor microenvironment (TME). Methods: Fourteen paraffin-embedded tissue samples of MCC were stratified by their MCPyV detection. Apart from PD-L1 and PD-1, the TME was further characterized for the expression of CD33, FOXP3 and MxA. Results: We observed PD-1 in 2 of 12 tumors. PD-L1 expression by tumor cells was found in 7 of 8 MCPyV(+) samples and was detected particularly in the periphery. The tumor cells were surrounded by a shield of PD-L1/CD33 immune cells. Expression of PD-L1 by the tumor cells was higher in areas with a denser immune infiltrate. CD33(+) cells without direct tumor contact were PD-L1 negative. Only a low number of FOXP3(+) regulatory T-cells was admixed. Tumor cells of MCPyV(â) samples were mostly PD-L1 negative. Conclusions: Our data demonstrate that PD-L1 expression occurs in tumor and immune cells, in areas in which they are close in contact. Interferon seems to play a role in this interaction. We postulate that PD-L1(+)/CD33(+) cells shield the tumor against attacking PD-1(+) immune cells. Therefore, next to anti-PD-1/PD-L1 antibodies, blockade of CD33 seems to be a promising therapeutic approach. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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