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- Bouyoucef, S E, et al.
(författare)
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Poster Session 2 : Monday 4 May 2015, 08
- 2015
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Franzen-Rohl, E., et al.
(författare)
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Herpes simplex virus specific T cell response in a cohort with primary genital infection correlates inversely with frequency of subsequent recurrences
- 2017
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Ingår i: Sexually Transmitted Infections. - : BMJ. - 1368-4973 .- 1472-3263. ; 93:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives During the last decades, a changing epidemiological pattern of genital herpes simplex virus (HSV) infection has emerged. Primary infection is now caused as often by HSV-1 as by HSV-2. Once established, HSV can be reactivated leading to recurrent mucocutaneous lesions as well as meningitis. Why some otherwise immune-competent individuals experience severe and frequent recurrences is not known, and the immunological mechanism underlying recurrent symptomatic HSV infection is not fully understood. In this study, we investigate and characterise the immune response of patients with first episode of HSV genital infection and its relation to the frequency of symptomatic recurrences. Methods In this cohort study, clinical and immunological data were collected from 29 patients who were followed 1 year after presenting with a first episode of genital or meningeal HSV infection. They were classified by PCR and serology as those with primary HSV-1, primary HSV-2 and non-primary HSV-2 infection. Results HSV-specific interleukin(Il)-4 and II-10 responses at first visit were higher in primary infected HSV-2 infected patients experiencing lower numbers of recurrences during subsequent year. Conclusions The median number of recurrences following primary HSV-2 genital infection may partly be predicted by the strength of an early HSV-specific IL-4 and IL-10 response.
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| 6. |
- Taghavi, K., et al.
(författare)
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Colposcopy telemedicine: live versus static swede score and accuracy in detecting CIN2+, a cross-sectional pilot study
- 2018
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Ingår i: Bmc Womens Health. - : Springer Science and Business Media LLC. - 1472-6874. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: This cross-sectional pilot study evaluates diagnostic accuracy of live colposcopy versus static image Swede-score evaluation for detecting significant precancerous cervical lesions greater than, or equal to grade 2 severity (CIN2+). Methods: VIA or HrHPV positive women were examined using a mobile colposcope, in a rural clinic in Kolkata, India. Live versus static Swede-score colposcopy assessments were made independently. All assessments were by gynecologists, junior or expert. Static image assessors were blinded to live scoring, patient information and final histopathology result. Primary outcome was the ability to detect CIN2+ lesions verified by directed biopsies. Diagnostic accuracy was calculated for live versus static Swede-score in detecting CIN2+ lesions, as well as for interclass correlation. Results: 495 images from 94 VIA positive women were evaluated in this study. Thirteen women (13.9%) had CIN2+ on biopsy. No significant difference was found in the detection of CIN2+ lesions between live and static assessors (area under curve = 0.69 versus 0.71, p = 0.63). A Swede-score of 4+, had a sensitivity of 76.9% (95% CI 46.2-95.0%) and 84.6% (95% CI 54.6-98.1%), for live-and static-image assessment respectively. The corresponding positive predictive values were found to be 90.9% (95% CI 75.7-98.1%) and 92.6% (95% CI 75.7-99.1%). The interclass correlation was good (kappa statistic = 0.60) for the senior static assessors. Conclusions: Swede-score evaluation of static colposcopy images was found to reliably detect CIN2+ lesions in this study. Larger studies are needed to further develop the colposcopy telemedicine concept which may offer reliable guidance in management where direct specialist input is not available. Trial registration: Ethical approval of the study was obtained by the Chittaranjan National Cancer Institute (CNCI) Human Research Ethics Committee (4.311/27/2014).
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| 10. |
- Enblad, Gunilla, et al.
(författare)
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A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia
- 2018
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 24:24, s. 6185-6194
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The chimeric antigen receptor (CAR) T-cell therapy has been effective for patients with CD19(+) B-cell malignancies. Most studies have investigated the second-generation CARs with either CD28 or 4-1BB costimulatory domains in the CAR receptor. Here, we describe the first clinical phase I/IIa trial using third-generation CAR T cells targeting CD19 to evaluate safety and efficacy.Patients and Methods: Fifteen patients with B-cell lymphoma or leukemia were treated with CAR T cells. The patients with lymphoma received chemotherapy during CAR manufacture and 11 of 15 were given low-dose cyclophosphamide and fludarabine conditioning prior to CAR infusion. Peripheral blood was sampled before and at multiple time points after CAR infusion to evaluate the persistence of CAR T cells and for immune profiling, using quantitative PCR, flow cytometry, and a proteomic array.Results: Treatment with third-generation CAR T cells was generally safe with 4 patients requiring hospitalization due to adverse reactions. Six of the 15 patients had initial complete responses [4/11 lymphoma and 2/4 acute lymphoblastic leukemia (ALL)], and 3 of the patients with lymphoma were in remission at 3 months. Two patients are still alive. Best predictor of response was a good immune status prior to CAR infusion with high IL12, DC-Lamp, Fas ligand, and TRAIL. Responding patients had low monocytic myeloid-derived suppressor cells (MDSCs; CD14(+)CD33(+)HLA(-)DR(-)) and low levels of IL6, IL8, NAP3, sPDL1, and sPDL2.Conclusions: Third-generation CARs may be efficient in patients with advanced B-cell lymphoproliferative malignancy with only modest toxicity. Immune profiling pre- and posttreatment can be used to find response biomarkers.
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| 11. |
- Herter, Eva K., et al.
(författare)
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WAKMAR2, a Long Noncoding RNA Downregulated in Human Chronic Wounds, Modulates Keratinocyte Motility and Production of Inflammatory Chemokines
- 2019
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Ingår i: Journal of Investigative Dermatology. - : ELSEVIER SCIENCE INC. - 0022-202X .- 1523-1747. ; 139:6, s. 1373-1384
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Tidskriftsartikel (refereegranskat)abstract
- Chronic wounds represent a major and growing health and economic burden worldwide. A better understanding of molecular mechanisms of normal as well as impaired wound healing is needed to develop effective treatment. Herein we studied the potential role of long noncoding RNA LOC100130476 in skin wound repair. LOC100130476 is an RNA polymerase IIeencoded polyadenylated transcript present in both cytoplasm and nucleus. We found that its expression was lower in wound-edge keratinocytes of human chronic wounds compared to normal wounds of healthy donors and intact skin. In cultured keratinocytes, LOC100130476 expression was induced by TGF-beta signaling. By reducing LOC100130476 expression with antisense oligos or activating its transcription with CRISPR/Cas9 Synergistic Activation Mediator system, we showed that LOC100130476 restricted the production of inflammatory chemokines by keratinocytes, while enhancing cell migration. In line with this, knockdown of LOC100130476 impaired re-epithelization of human ex vivo wounds. Based on these results, we named LOC100130476 wound and keratinocyte migration-associated long noncoding RNA 2 (WAKMAR2). Moreover, we identified a molecular network that may mediate the biological function of WAKMAR2 in keratinocytes using microarray. In summary, our data suggest that WAKMAR2 is an important regulator of skin wound healing and its deficiency may contribute to the pathogenesis of chronic wounds.
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| 12. |
- Li, Dongqing, et al.
(författare)
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Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:19, s. 9443-9452
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Tidskriftsartikel (refereegranskat)abstract
- An increasing number of studies reveal the importance of long noncoding RNAs (lncRNAs) in gene expression control underlying many physiological and pathological processes. However, their role in skin wound healing remains poorly understood. Our study focused on a skin-specific lncRNA, LOC105372576, whose expression was increased during physiological wound healing. In human nonhealing wounds, however, its level was significantly lower compared with normal wounds under reepithelialization. We characterized LOC105372576 as a nuclear-localized, RNAPII-transcribed, and polyadenylated lncRNA. In keratinocytes, its expression was induced by TGF-beta signaling. Knockdown of LOC105372576 and activation of its endogenous transcription, respectively, reduced and increased the motility of keratinocytes and reepithelialization of human ex vivo skin wounds. Therefore, LOC105372576 was termed "wound and keratinocyte migration-associated lncRNA 1" (WAKMAR1). Further study revealed that WAKMAR1 regulated a network of protein-coding genes important for cell migration, most of which were under the control of transcription factor E2F1. Mechanistically, WAKMAR1 enhanced E2F1 expression by interfering with E2F1 promoter methylation through the sequestration of DNA methyltransferases. Collectively, we have identified a lncRNA important for keratinocyte migration, whose deficiency may be involved in the pathogenesis of chronic wounds.
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| 13. |
- Olofsson, Mona, et al.
(författare)
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A description of characteristics of very elderly patients newly diagnosed with heart failure : a retrospective population-based cohort study in Sweden
- 2017
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Ingår i: European Journal of Heart Failure. - : European Society of Cardiology. - 1388-9842 .- 1879-0844. ; 19:S1, s. 362-362
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Over a quarter of patients with heart failure (HF) in Sweden are very elderly (defined as aged ≥85 years). Evidence on the demographic and clinical characteristics of these patients, and on the diagnostic procedures they receive in clinical practice, is scarce.Methods: Patients with HF were identified via electronic medical records from primary and/or secondary care in Västerbotten, linked via unique identifiers to data from the National Patient Register and Swedish Prescribed Drug Register. Local echocardiography data were used to identify patients with HF with preserved (HFpEF, ≥50%) and reduced (HFrEF, <50%) ejection fraction. Patients aged ≥18 years with ≥2 diagnoses of HF between 01/01/2010 and 31/03/2015 and an ICD-10 diagnostic code of I50 (inclusive of all granular codes), I42.0, I42.6, I42.7, I42.9, I110, I130 or I132 in any position were included. The date of the first diagnosis was the index date. ICD-10 codes were also used to identify comorbidities. A 10-year look-back period was used to exclude prevalent HF cases. Patient characteristics were assessed at index, except comorbidities (in the 5 years before index) and pre-diagnosis comedications (in the first year before index).Results: In total, 8702 patients with HF were identified; 27.7% were aged ≥85 years. Compared with patients <85 years, more patients ≥85 years were female (60.2% vs 40.6%) and fewer were overweight (BMI >25 kg/m2, 42.3% vs 63.5%). In both groups, HF was more commonly diagnosed in secondary than in primary care, but patients ≥85 years were more often diagnosed in primary care than those <85 years (31.2% vs 20.9%). Fewer patients ≥85 years than those <85 years received an echocardiogram at diagnosis (19.3% vs 42.9%); of those who did, more patients ≥85 years than <85 years had HFpEF (46.8% vs 33.4%). Patients ≥85 years had a comorbidity burden similar to those <85 years (mean number of comorbidities/patient, 2.4 vs 2.3); prevalence of atrial fibrillation (32.0% vs 30.4%), hypertension (53.2% vs 53.0%) and ischaemic heart disease (20.5% vs 22.5%) were also similar in both age groups. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and systolic blood pressure (BP) increased with age, and diastolic BP and estimated glomerular filtration rate decreased. Potassium and sodium levels did not differ between age groups (Table). The most common pre-diagnosis comedications were ?-blockers, antithrombotic agents and diuretics; ?-blockers were less frequently prescribed in patients ≥85 years (59.6% vs 64.4%), and antithrombotic agents and diuretics were more frequently prescribed in those ≥85 years (antithrombotic agents, 57.0% vs 54.3%; diuretics, 50.1% vs 43.1%).Conclusions: Very elderly patients with HF in Sweden are clinically different from younger patients, with a higher prevalence of HFpEF and higher NT-proBNP levels (as expected). Most importantly, very elderly patients seldom receive an echocardiogram at diagnosis.
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| 14. |
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| 15. |
- Wikstrom, G., et al.
(författare)
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Drug treatment patterns in patients newly diagnosed with heart failure : a retrospective population-based cohort study in Sweden
- 2017
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Ingår i: European Journal of Heart Failure. - : European Society of Cardiology. - 1388-9842 .- 1879-0844. ; 19:S1, s. 55-55
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Limited data are available on longitudinal drug treatment patterns in newly diagnosed patients with heart failure (HF) with preserved (HFpEF), reduced (HFrEF) and unknown ejection fraction (EF) in Sweden. We evaluated drug treatment patterns in these patients based on ESC 2012 guidelines, which recommend treatment with angiotensin-converting enzyme inhibitors (ACEis), angiotensin II receptor blockers (ARBs), ?-blockers (BBs) and mineralocorticoid receptor antagonists (MRAs) for HFrEF (ESC does not make recommendations for HFpEF or unknown EF).Methods: Patients were identified via electronic medical records from primary and/or secondary care in Västerbotten, linked via unique identifiers to the National Patient Register and Swedish Prescribed Drug Register. Local echocardiography data identified HFrEF (<50%) and HFpEF (≥50%). Patients aged ≥18 years with ≥2 diagnoses of HF between 01/01/2010 and 31/03/2015 and an ICD-10 diagnostic code of I50 (inclusive of all granular codes), I42.0, I42.6, I42.7, I42.9, I110, I130 or I132 in any position were included. The date of the first diagnosis was defined as the index date. A 10-year look-back period was used to exclude prevalent HF cases. ATC codes were identified from drug prescriptions. Patients with a 4-year look-back and 2 years of follow-up were included.Results: Overall, 4357 patients were included (mean± SD age, 76.6± 12.6 years; 27.7% aged ≥85 years; HFrEF, 24.6%; HFpEF, 12.9%; unknown EF, 62.5%). At the index date, 63.0% of patients were treated with an ACEi or an ARB, 62.3% with a BB and 16.0% with an MRA; 18.5% were not receiving treatment. The most common treatment groups (monotherapy or combinations) were: ACEi + BB (HFrEF, 20.5%; HFpEF, 21.0%; unknown EF, 23.5%); BB monotherapy (HFrEF, 12.1%; HFpEF, 14.0%; unknown EF, 15.6%); and ARB + BB (HFrEF, 8.5%; HFpEF, 12.3%; unknown EF, 12.3%) (Figure). The majority of patients receiving an ACEi or ARB at the index date continued to do so for the following 2 years (ACEi, 63.6%; ARB, 60.9%); most of these were receiving doses lower than those recommended by the ESC (70.8% and 88.9%, respectively). A small proportion of patients receiving an ACEi at the index date switched to an ARB over the 2-year period (4.1%) and vice versa (2.6%). Most patients were not receiving the recommended ESC dose before switching (ACEi, 81.8%; ARB, 77.8%). Similarly, most patients who discontinued an ACEi (37.3%) or ARB (39.1%) were not receiving the recommended dose before discontinuation (ACEi, 64.8%; ARB, 87.4%).Conclusions: A large proportion of patients with HF in Sweden do not receive drug combinations recommended by the ESC. Furthermore, few patients are prescribed ESC-recommended doses of HF drugs and few undergo up-titration of treatment before switching. These findings are remarkable for HFrEF, for which guidelines are established. These findings may be partly reflective of the high proportion of elderly patients studied.
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