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| 12. |
- Stray-Pedersen, Asbjorg, et al.
(författare)
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Primary immunodeficiency diseases : Genomic approaches delineate heterogeneous Mendelian disorders
- 2017
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Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 139:1, s. 232-245
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective: We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. Methods: Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results: A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/ 110) and management was directly altered in nearly a quarter (26/ 110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion: This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.
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| 16. |
- Calon, T. G. A., et al.
(författare)
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Minimally Invasive Ponto Surgery Versus the Linear Incision Technique With Soft Tissue Preservation for Bone Conduction Hearing Implants: A Multicenter Randomized Controlled Trial
- 2018
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Ingår i: Otology & Neurotology. - : Ovid Technologies (Wolters Kluwer Health). - 1531-7129 .- 1537-4505. ; 39:7, s. 882-893
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To compare the surgical outcomes of the Minimally Invasive Ponto Surgery (MIPS) technique with those of the linear incision technique with soft-tissue preservation for bone-anchored hearing systems (BAHS).Design:Sponsor-initiated multicenter, open, randomized, controlled clinical trial.Setting:Maastricht University Medical Centre, Ziekenhuisgroep Twente and Medisch Centrum Leeuwarden, all situated in The Netherlands.Participants:Sixty-four adult patients eligible for unilateral BAHS surgery.Interventions Single-stage BAHS surgery with 1:1 randomization to the linear incision technique with soft-tissue preservation (control) or the MIPS (test) group.Primary and Secondary Outcome Measurements:Primary objective: compare the incidence of inflammation (Holgers Index 2) during 12 weeks' follow-up after surgery. Secondary objectives: skin dehiscence, pain scores, loss of sensibility around the implant, soft-tissue overgrowth, skin sagging, implant extrusion, cosmetic results, surgical time, wound healing and Implant Stability Quotient measurements.Results:Sixty-three subjects were analyzed in the intention-to-treat population. No significant difference was found for the incidence of inflammation between groups. Loss of skin sensibility, cosmetic outcomes, skin sagging, and surgical time were significantly better in the test group. No statistically significant differences were found for dehiscence, pain, and soft-tissue overgrowth. A nonsignificant difference in extrusion was found for the test group. The Implant Stability Quotient was statistically influenced by the surgical technique, abutment length, and time.Conclusion:No significant differences between the MIPS and the linear incision techniques were observed regarding skin inflammation. MIPS results in a statistically significant reduction in the loss of skin sensibility, less skin sagging, improved cosmetic results, and reduced surgical time. Although nonsignificant, the implant extrusion rate warrants further research.
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| 18. |
- Klyuchnikov, Evgeny, et al.
(författare)
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Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors
- 2015
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 21:12, s. 2091-2099
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Tidskriftsartikel (refereegranskat)abstract
- This study was conducted to compare long-term outcomes in patients with refractory/relapsed grades 1 and 2 follicular lymphoma (FL) after allogeneic (allo) versus autologous (auto) hematopoietic cell transplantation (HCT) in the rituximab era. Adult patients with relapsed/refractory grades 1 and 2 FL undergoing first reduced-intensity allo-HCT or first autograft during 2000 to 2012 were evaluated. A total of 518 rituximab-treated patients were included. Allo-HCT patients were younger and more heavily pretreated, and more patients had advanced stage and chemoresistant disease. The 5-year adjusted probabilities, comparing auto-HCT versus allo-HCT groups for nonrelapse mortality (NRM) were 5% versus 26% (P <.0001); relapse/progression: 54% versus 20% (P <.0001); progression-free survival (PFS): 41% versus 58% (P <.001), and overall survival (OS): 74% versus 66% (P =.05). Auto-HCT was associated with a higher risk of relapse/progression beyond 5 months after HCT (relative risk [RR], 4.4; P <.0001) and worse PFS (RR, 2.9; P <.0001) beyond 11 months after HCT. In the first 24 months after HO', auto-HCT was associated with improved OS (RR,.41; P <.0001), but beyond 24 months, it was associated with inferior OS (RR, 2.2; P =.006). A landmark analysis of patients alive and progression-free at 2 years after HO' confirmed these observations, showing no difference in further NRM between both groups, but there was significantly higher risk of relapse/progression (RR, 7.3; P <.0001) and inferior PFS (RR, 3.2; P <.0001) and OS (RR, 2.1; P =.04) after auto-HCT. The 10-year cumulative incidences of second hematological malignancies after allo-HCT and auto-HCT were 0% and 7%, respectively. Auto-HCT and reduced-intensity conditioned allo-HCT as first transplantation approach can provide durable disease control in grades 1 and 2 FL patients. Continued disease relapse risk after auto-HCT translates into improved PFS and OS after allo-HCT in long-term survivors.
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