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- Jehi, L., et al.
(författare)
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Timing of referral to evaluate for epilepsy surgery: Expert Consensus Recommendations from the Surgical Therapies Commission of the International League Against Epilepsy
- 2022
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 63:10, s. 2491-2506
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Tidskriftsartikel (refereegranskat)abstract
- Epilepsy surgery is the treatment of choice for patients with drug-resistant seizures. A timely evaluation for surgical candidacy can be life-saving for patients who are identified as appropriate surgical candidates, and may also enhance the care of nonsurgical candidates through improvement in diagnosis, optimization of therapy, and treatment of comorbidities. Yet, referral for surgical evaluations is often delayed while palliative options are pursued, with significant adverse consequences due to increased morbidity and mortality associated with intractable epilepsy. The Surgical Therapies Commission of the International League Against Epilepsy (ILAE) sought to address these clinical gaps and clarify when to initiate a surgical evaluation. We conducted a Delphi consensus process with 61 epileptologists, epilepsy neurosurgeons, neurologists, neuropsychiatrists, and neuropsychologists with a median of 22 years in practice, from 28 countries in all six ILAE world regions. After three rounds of Delphi surveys, evaluating 51 unique scenarios, we reached the following Expert Consensus Recommendations: (1) Referral for a surgical evaluation should be offered to every patient with drug-resistant epilepsy (up to 70 years of age), as soon as drug resistance is ascertained, regardless of epilepsy duration, sex, socioeconomic status, seizure type, epilepsy type (including epileptic encephalopathies), localization, and comorbidities (including severe psychiatric comorbidity like psychogenic nonepileptic seizures [PNES] or substance abuse) if patients are cooperative with management; (2) A surgical referral should be considered for older patients with drug-resistant epilepsy who have no surgical contraindication, and for patients (adults and children) who are seizure-free on 1-2 antiseizure medications (ASMs) but have a brain lesion in noneloquent cortex; and (3) referral for surgery should not be offered to patients with active substance abuse who are noncooperative with management. We present the Delphi consensus results leading up to these Expert Consensus Recommendations and discuss the data supporting our conclusions. High level evidence will be required to permit creation of clinical practice guidelines.
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| 2. |
- Laurie, K. L., et al.
(författare)
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Cell-specific and efficient expression in mouse and human B cells by a novel hybrid immunoglobulin promoter in a lentiviral vector
- 2007
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Ingår i: Gene Therapy. - : Springer Science and Business Media LLC. - 0969-7128 .- 1476-5462. ; 14:23, s. 1623-1631
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Tidskriftsartikel (refereegranskat)abstract
- The expression of genes specifically in B cells is of great interest in both experimental immunology as well as in future clinical gene therapy. We have constructed a novel enhanced B cell-specific promoter (Igk- E) consisting of an immunoglobulin kappa (Igk) minimal promoter combined with an intronic enhancer sequence and a 30 enhancer sequence from Ig genes. The Igk- E promoter was cloned into a lentiviral vector and used to control expression of enhanced green fluorescent protein (eGFP). Transduction of murine B-cell lymphoma cell lines and activated primary splenic B cells, with IgK-E-eGFP lentivirus, resulted in expression of eGFP, as analysed by flow cytometry, whereas expression in non-B cells was absent. The specificity of the promoter was further examined by transducing Lin bone marrow with Igk-E-eGFP lentivirus and reconstituting lethally irradiated mice. After 16 weeks flow cytometry of lymphoid tissues revealed eGFP expression by CD19(+) cells, but not by CD3(+), CD11b(+), CD11c(+) or Gr-1(+) cells. CD19(+) cells were comprised of both marginal zone B cells and recirculating follicular B cells. Activated human peripheral mononuclear cells were also transduced with Igk-E-eGFP lentivirus under conditions of selective B-cell activation. The Igk-E promoter was able to drive expression of eGFP only in CD19(+) cells, while eGFP was expressed by both spleen focus forming virus and cytomegalovirus constitutive promoters in CD19(+) and CD3(+) lymphocytes. These data demonstrate that in these conditions the Igk-E promoter is cell specific and controls efficient expression of a reporter protein in mouse and human B cells in the context of a lentiviral vector.
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| 3. |
- Hill, S C, et al.
(författare)
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Activation of CD40 in cervical carcinoma cells facilitates CTL responses and augments chemotherapy-induced apoptosis
- 2005
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Ingår i: Journal of Immunology. - 1550-6606. ; 174:1, s. 41-50
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we describe the expression and function of CD40, a TNF receptor family member, in cervical carcinomas. CD40 was present at very low levels in normal cervical epithelium but was overexpressed in human papillomavirus-infected lesions and advanced squamous carcinomas of the cervix. The stimulation of CD40-positive cervical carcinoma cell lines with soluble CD40L (CD154) resulted in activation of the NF-kappaB and MAPK signaling pathways and up-regulation of cell surface markers and intracellular molecules associated with Ag processing and presentation. Concomitantly, the CD154-induced activation of CD40 in carcinoma cells was found to directly influence susceptibility to CTL-mediated killing. Thus, CD40 stimulation in cervical carcinoma cell lines expressing a TAP-dependent human papillomavirus 16 E6 Ag epitope resulted in their enhanced killing by specific CTLs. However, CD154 treatment of carcinoma cells expressing proteasome-dependent but TAP-independent Ags from the EBV-encoded BRLF1 and BMLF1 failed to increase tumor cell lysis by specific CTLs. Moreover, we demonstrate that chemotherapeutic agents that suppress protein synthesis and reverse the CD40-mediated dissociation of the translational repressor eukaryotic initiation factor 4E-binding protein from the initiation factor eukaryotic initiation factor 4E, such as 5-fluorouracil, etoposide, and quercetin, dramatically increase the susceptibility of cervical carcinoma cells to CD40L-induced apoptosis. Taken together, these observations demonstrate the functional expression of CD40 in epithelial tumors of the cervix and support the clinical exploitation of the CD40 pathway for the treatment of cervical cancer through its multiple effects on tumor cell growth, apoptosis, and immune recognition.
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| 7. |
- Malmgren, Kristina, 1952, et al.
(författare)
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Long-term outcomes of epilepsy surgery in adults and children
- 2015
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- This book provides a comprehensive, rigorous review of the long-term outcome literature in epilepsy surgery in both adults and children. Each chapter examines the long-term outcome literature in a separate domain; covering seizure control, social, vocational/educational and psychiatric outcomes. Behavior and cognition are also discussed. The clinical predictors of good and bad outcomes in each domain are described and the gaps in current knowledge are highlighted. Separate chapters examine the methodological challenges associated with long-term outcome studies and the special considerations associated with informed consent in this population. Long-Term Outcomes of Epilepsy Surgery in Adults and Children is essential reading for all members of multidisciplinary epilepsy surgery teams, including neurosurgeons, neurologists and neuropsychologists; it will enable these teams to counsel patients and parents who are considering epilepsy surgery as a therapeutic option.
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| 8. |
- Malmgren, Kristina, 1952, et al.
(författare)
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Long-term outcomes of epilepsy surgery: Knowledge gaps and future directions
- 2015
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Ingår i: Long-Term Outcomes of Epilepsy Surgery in Adults and Children. - Cham : Springer. - 9783319177830 ; , s. 269-275
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Bokkapitel (refereegranskat)abstract
- Although epilepsy surgery has long been recognized as an effective treatment for carefully selected adults and children, studies of long-term seizure control are relatively rare and studies of the wider aspects of surgical outcome are even more scarce. In summarizing the literature, many of the chapters in this volume have highlighted what we do not know about epilepsy surgery outcomes rather than what we do. This chapter highlights the gaps in the adult and pediatric literature and discusses the roles that networking, collaboration, and adherence to a basic set of standards may play in addressing the current shortcomings of the literature. © Springer International Publishing Switzerland 2015.
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| 9. |
- Malmgren, Kristina, 1952, et al.
(författare)
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Why a volume on long-term outcomes of epilepsy surgery?
- 2015
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Ingår i: Long-Term Outcomes of Epilepsy Surgery in Adults and Children. - Cham : Springer. - 9783319177830 ; , s. 1-4
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Bokkapitel (refereegranskat)abstract
- Epilepsy surgery is a recognized option in the management of adults and children with drug-resistant epilepsy. Magnetic resonance imaging has increased the number of candidates by determining focal structural brain abnormalities not previously apparent. Advances in other techniques have widened the spectrum of surgical candidates both in adults and children. In the short term, rates of seizure freedom are relatively high, but seizure recurrence can still occur in the long term. There are methodological hurdles to overcome when assessing longer-term outcome. There are also the outcomes beyond seizures-cognition, neurodevelopment, academic and vocational outcomes, and quality of life-which are of importance when determining whether a treatment is benefi cial. The aim of this volume is to focus on longer-term outcomes from epilepsy surgery in both adults and children. © Springer International Publishing Switzerland 2015.
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