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| 2. |
- Ken-Dror, G., et al.
(författare)
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Genome-Wide Association Study Identifies First Locus Associated with Susceptibility to Cerebral Venous Thrombosis
- 2021
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 90:5, s. 777-788
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Tidskriftsartikel (refereegranskat)abstract
- Objective Cerebral venous thrombosis (CVT) is an uncommon form of stroke affecting mostly young individuals. Although genetic factors are thought to play a role in this cerebrovascular condition, its genetic etiology is not well understood. Methods A genome-wide association study was performed to identify genetic variants influencing susceptibility to CVT. A 2-stage genome-wide study was undertaken in 882 Europeans diagnosed with CVT and 1,205 ethnicity-matched control subjects divided into discovery and independent replication datasets. Results In the overall case-control cohort, we identified highly significant associations with 37 single nucleotide polymorphisms (SNPs) within the 9q34.2 region. The strongest association was with rs8176645 (combined p = 9.15 x 10(-24); odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.76-2.31). The discovery set findings were validated across an independent European cohort. Genetic risk score for this 9q34.2 region increases CVT risk by a pooled estimate OR = 2.65 (95% CI = 2.21-3.20, p = 2.00 x 10(-16)). SNPs within this region were in strong linkage disequilibrium (LD) with coding regions of the ABO gene. The ABO blood group was determined using allele combination of SNPs rs8176746 and rs8176645. Blood groups A, B, or AB, were at 2.85 times (95% CI = 2.32-3.52, p = 2.00 x 10(-16)) increased risk of CVT compared with individuals with blood group O. Interpretation We present the first chromosomal region to robustly associate with a genetic susceptibility to CVT. This region more than doubles the likelihood of CVT, a risk greater than any previously identified thrombophilia genetic risk marker. That the identified variant is in strong LD with the coding region of the ABO gene with differences in blood group prevalence provides important new insights into the pathophysiology of CVT. ANN NEUROL 2021
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| 3. |
- Ranjan, R., et al.
(författare)
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Age of onset of cerebral venous thrombosis: the BEAST study
- 2023
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Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 8:1, s. 344-350
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke in young adults. We aimed to determine the impact of age, gender and risk factors (including sex-specific) on CVT onset. Methods: We used data from the BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis), a multicentre multinational prospective observational study on CVT. Composite factors analysis (CFA) was performed to determine the impact on the age of CVT onset in males and females. Results: A total of 1309 CVT patients (75.3% females) aged > 18 years were recruited. The overall median (IQR-interquartile range) age for males and females was 46 (35-58) years and 37 (28-47) years (p < 0.001), respectively. However, the presence of antibiotic-requiring sepsis (p = 0.03, 95% CI 27-47 years) among males and gender-specific risk factors like pregnancy (p < 0.001, 95% CI 29-34 years), puerperium (p < 0.001, 95% CI 26-34 years) and oral contraceptive use (p < 0.001, 95% CI 33-36 years) were significantly associated with earlier onset of CVT among females. CFA demonstrated a significantly earlier onset of CVT in females, similar to 12 years younger, in those with multiple (> 1) compared to '0' risk factors (p < 0.001, 95% CI 32-35 years). Conclusions: Women suffer CVT 9 years earlier in comparison to men. Female patients with multiple (> 1) risk factors suffer CVT similar to 12 years earlier compared to those with no identifiable risk factors.
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- Kald, A, et al.
(författare)
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Reoperation as surrogate endpoint in hernia surgery. A three year follow-up of 1565 herniorrhaphies.
- 1998
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Ingår i: European Journal of Surgery. - : Oxford University Press (OUP). - 1102-4151 .- 1741-9271. ; 164:1, s. 45-50
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Analysis of reoperation and recurrence rates three years after repair of groin hernias.DESIGN: Prospective audit by questionnaire and selective follow-up.SETTING: Eight Swedish hospitals.SUBJECTS: All groin hernia operations done during 1992 on patients between the ages of 15 and 80 years.MAIN OUTCOME MEASURES: Postoperative complications, reoperation for recurrence, and recurrence.RESULTS: During 1992, 1565 hernia operations were done. The postoperative complication rate was 8% (125/1565). At 36 months postoperatively 108 recurrences had already been reoperated on, six patients with recurrences were on the waiting list for reoperation and a further 36 recurrences had been detected at follow-up. The interhospital variation in recurrence rate ranged from 3% to 20%. Postoperative complications, recurrent hernia, direct hernia and hospital catchment area over 100000 inhabitants were all factors associated with an increased relative risk of recurrence.CONCLUSIONS: The recurrence rate exceeded the reoperation rate for recurrence by almost 40% which should be taken into account if the reoperation rate is used as the endpoint after repairs of groin hernia. An audit scheme, based on prospective recording, reoperation rate, and (periodic) calculation of the recurrence rate may be used to identify risk factors for recurrence and areas in need of improvement.
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| 9. |
- Flanagan, Sarah E, et al.
(författare)
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Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease.
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 46:8, s. 812-814
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Tidskriftsartikel (refereegranskat)abstract
- Monogenic causes of autoimmunity provide key insights into the complex regulation of the immune system. We report a new monogenic cause of autoimmunity resulting from de novo germline activating STAT3 mutations in five individuals with a spectrum of early-onset autoimmune disease, including type 1 diabetes. These findings emphasize the critical role of STAT3 in autoimmune disease and contrast with the germline inactivating STAT3 mutations that result in hyper IgE syndrome.
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| 15. |
- Kallionpaa, R. A., et al.
(författare)
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Mast Cells in Human Cutaneous Neurofibromas: Density, Subtypes, and Association with Clinical Features in Neurofibromatosis 1
- 2022
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Ingår i: Dermatology. - : S. Karger AG. - 1018-8665 .- 1421-9832. ; 238:2, s. 329-339
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cutaneous neurofibromas (cNFs) are hallmarks of neurofibromatosis 1 (NF1) and cause the main disease burden in adults with NF1. Mast cells are a known component of cNFs. However, no comprehensive characterization of mast cells in cNFs is available, and their contributions to cNF growth and symptoms such as itch are not known. Methods: We collected 60 cNFs from ten individuals with NF1, studied their mast cell proteinase content, and compared the mast cell numbers to selected clinical features of the tumors and patients. The tumors were immunolabeled for the mast cell markers CD117, tryptase, and chymase, and the percentage of immunopositive cells was determined using computer-assisted methods. Results: The median proportions of positive cells were 5.5% (range 0.1-14.4) for CD117, 4.0% (1.2-7.0) for tryptase, and 5.0% (1.1-15.9) for chymase. The median densities of cells immunopositive for CD117, tryptase, and chymase were 280, 243, and 250 cells/mm(2), respectively. Small tumors, growing tumors, and tumors from patients below the median age of 33 years displayed a high proportion of mast cells. Cells expressing both tryptase and chymase were the predominant mast cell type in cNFs, followed by cells expressing chymase only. Conclusion: The results highlight the abundance of mast cells in cNFs and that their number and subtypes clearly differ from those previously reported in unaffected skin.
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| 19. |
- Keskitalo, S, et al.
(författare)
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Dominant TOM1 mutation associated with combined immunodeficiency and autoimmune disease
- 2019
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Ingår i: NPJ genomic medicine. - : Springer Science and Business Media LLC. - 2056-7944. ; 4, s. 14-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Mutations in several proteins functioning as endolysosomal components cause monogenic autoimmune diseases, of which pathogenesis is linked to increased endoplasmic reticulum stress, inefficient autophagy, and defective recycling of immune receptors. We report here a heterozygous TOM1 p.G307D missense mutation, detected by whole-exome sequencing, in two related patients presenting with early-onset autoimmunity, antibody deficiency, and features of combined immunodeficiency. The index patient suffered from recurrent respiratory tract infections and oligoarthritis since early teens, and later developed persistent low-copy EBV-viremia, as well as an antibody deficiency. Her infant son developed hypogammaglobulinemia, autoimmune enteropathy, interstitial lung disease, profound growth failure, and treatment-resistant psoriasis vulgaris. Consistent with previous knowledge on TOM1 protein function, we detected impaired autophagy and enhanced susceptibility to apoptosis in patient-derived cells. In addition, we noted diminished STAT and ERK1/2 signaling in patient fibroblasts, as well as poor IFN-γ and IL-17 secretion in T cells. The mutant TOM1 failed to interact with TOLLIP, a protein required for IL-1 recycling, PAMP signaling and autophagosome maturation, further strengthening the link between the candidate mutation and patient pathophysiology. In sum, we report here an identification of a novel gene, TOM1, associating with early-onset autoimmunity, antibody deficiency, and features of combined immunodeficiency. Other patient cases from unrelated families are needed to firmly establish a causal relationship between the genotype and the phenotype.
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| 20. |
- Koch Frisén, Angelica, et al.
(författare)
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Prospective evaluation of 6895 groin hernia repairs in women
- 2005
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 92:12, s. 1553-1558
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although 8 per cent of groin hernia repairs are performed in women, there is little published literature relating specifically to women. This study compared differences in outcome between women and men after groin hernia repair.Methods: Data collected prospectively in the Swedish Hernia Register between 1992 and 2003 were analysed, including 6895 groin hernia repairs in women and 83 753 in men.Results: A higher proportion of emergency operations was carried out in women (16.9 per cent) than men (5.0 per cent), leading to bowel resection in 16.6 and 5.6 per cent respectively. During reoperation femoral hernias were found in 41.6 per cent of the women who were diagnosed with a direct or indirect inguinal hernia at the primary operation. The corresponding proportion for men was 4.6 per cent. The hernia repair was not classified as a standard operation (e.g. Shouldice, Lichtenstein, Plug/Mesh, TAPP/TEP) in 38.2 per cent of women and 11.2 per cent of men. Women had a significantly higher risk of reoperation for recurrence than men, and techniques associated with the lowest risk for reoperation in men had the highest risk in women.Conclusion: A greater proportion of women than men require emergency groin hernia repair, with consequently higher rates of bowel resection, complications and death. Surgical techniques developed for use in men may put women at unnecessary risk. Copyright © 2005 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.
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| 22. |
- Nordin, P, et al.
(författare)
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Influence of suture material and surgical technique on risk of reoperation after non-mesh open hernia repair
- 2003
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 90:8, s. 1004-1008
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although mesh techniques are used with increasing frequency, sutured repair still has a place in groin hernia surgery. Studies relating suture material to recurrence rate have yielded conflicting results. The aim of the present study was to analyse the influence of suture material and sutured non-mesh technique on the risk of reoperation in open groin hernia repair using data from the Swedish Hernia Register. Methods: The relative risk of reoperation after sutured repair using non-absorbable, late absorbable and early absorbable sutures was compared in multivariate analyses, taking into account known confounding factors. Results: Between 1992 and 2000, 46 745 hernia repairs were recorded in the Swedish Hernia Register. Of these, 18 057 repairs were performed with open non-mesh methods and were included in the analysis. Using non-absorbable suture as reference, the relative risk of reoperation after repair with early absorbable suture and late absorbable suture was 1.50 (95 per cent confidence interval (c.i.) 1.22 to 1.83) and 1.03 (95 per cent c.i. 0.83 to 1.28) respectively. Using the Shouldice repair as reference, other sutured repairs were associated with a significantly higher relative risk of reoperation (1.22, 95 per cent c.i. 1.03 to 1.44). Conclusion: A non-absorbable or a late absorbable suture is recommended for open non-mesh groin hernia repair. The Shouldice technique was found to be superior to other open methods.
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| 23. |
- Oksa, L, et al.
(författare)
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Arginine Methyltransferase PRMT7 Deregulates Expression of RUNX1 Target Genes in T-Cell Acute Lymphoblastic Leukemia
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with no well-established prognostic biomarkers. We examined the expression of protein arginine methyltransferases across hematological malignancies and discovered high levels of PRMT7 mRNA in T-ALL, particularly in the mature subtypes of T-ALL. The genetic deletion of PRMT7 by CRISPR-Cas9 reduced the colony formation of T-ALL cells and changed arginine monomethylation patterns in protein complexes associated with the RNA and DNA processing and the T-ALL pathogenesis. Among them was RUNX1, whose target gene expression was consequently deregulated. These results suggest that PRMT7 plays an active role in the pathogenesis of T-ALL.
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| 24. |
- Raty, S., et al.
(författare)
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Occipital intracerebral hemorrhage-clinical characteristics, outcome, and post-ICH epilepsy
- 2021
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 143:1, s. 71-77
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Posterior location affects the clinical presentation and outcome of ischemic stroke, but little is known about occipital intracerebral hemorrhage (ICH). We studied non-traumatic occipital ICH phenotype, outcome, and post-ICH epilepsy. Materials and Methods Occipital ICH patients were retrospectively identified from the Helsinki ICH Study registry of 1013 consecutive ICH patients treated in our tertiary center in 2005-2010. They were compared to non-occipital ICH patients to evaluate the effect of location on functional outcome at discharge (dichotomized modified Rankin Scale, mRS), 3- and 12-month mortality, and incidence of epilepsy. Results We found 19 occipital ICH patients (5.3% of lobar and 1.9% of all ICH). Compared to non-occipital lobar ICHs, they were younger (median age 63 vs 71 years,P= .007) and had lower National Institutes of Health Stroke Scale on admission (1 vs 8,P< .001), smaller hematoma volume (6.3 vs 17.7 ML,P= .008), and more frequently structural etiology underlying the ICH (26% vs 7%,P= .01). Mortality at both 3 and 12 months was 6%, whereas 84% reached favorable outcome (mRS 0-2) at discharge. Occipital location was associated with favorable outcome at discharge in lobar ICH (OR 11.02, 95% CI 1.55-78.20). Incidence of post-ICH epilepsy (median follow-up 2.7 years) was 18%, equaling to that of non-occipital lobar ICH. Conclusions Occipital ICH patients are younger, have less severe clinical presentation, smaller hematoma volume, more often structural etiology, and better outcome than other ICH patients. They exhibit a similar risk of epilepsy as non-occipital ICHs.
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| 25. |
- Vahamurto, P, et al.
(författare)
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Clinical findings of extranodal SNT lymphoid malignancies in a four-decade single-centre series
- 2016
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Ingår i: European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. - : Springer Science and Business Media LLC. - 1434-4726. ; 273:11, s. 3839-3845
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Tidskriftsartikel (refereegranskat)
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