| 1. |
- Brunkwall, Louise, et al.
(författare)
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The Malmö Offspring Study (MOS) : design, methods and first results.
- 2021
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Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 36, s. 103-116
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Tidskriftsartikel (refereegranskat)abstract
- As cardio metabolic disease manifestations tend to cluster in families there is a need to better understand the underlying mechanisms in order to further develop preventive strategies. In fact, genetic markers used in genetic risk scores, important as they are, will not be able alone to explain these family clusters. Therefore, the search goes on for the so called missing heritability to better explain these associations. Shared lifestyle and social conditions in families, but also early life influences may be of importance. Gene-environmental interactions should be explored. In recent years interest has grown for the role of diet-microbiota associations, as microbiota patterns may be shared by family members. In the Malmö Offspring Study that started in 2013, we have so far been able to examine about 4700 subjects (18-71 years) representing children and grandchildren of index subjects from the first generation, examined in the Malmö Diet Cancer Study during 1991 to 1996. This will provide rich data and opportunities to analyse family traits of chronic disease across three generations. We will provide extensive genotyping and phenotyping including cardiovascular and respiratory function, as well as markers of glucose metabolism. In addition, also cognitive function will be assessed. A 4-day online dietary recall will be conducted and gut as well as oral microbiota analysed. The ambition is to provide one of the first large-scale European family studies with individual data across three generations, which could deepen our knowledge about the role of family traits for chronic disease and its underlying mechanisms.
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| 2. |
- Karlsson, Joakim, et al.
(författare)
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Molecular profiling of driver events in metastatic uveal melanoma
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Metastatic uveal melanoma is less well understood than its primary counterpart, has a distinct biology compared to skin melanoma, and lacks effective treatments. Here we genomically profile metastatic tumors and infiltrating lymphocytes. BAP1 alterations are overrepresented and found in 29/32 of cases. Reintroducing a functional BAP1 allele into a deficient patient-derived cell line, reveals a broad shift towards a transcriptomic subtype previously associated with better prognosis of the primary disease. One outlier tumor has ahigh mutational burden associated with UV-damage. CDKN2A deletions also occur, which are rarely present in primaries. A focused knockdown screen is used to investigate overexpressed genesassociated withcopy number gains. Tumor-infiltrating lymphocytes are in several cases found tumor-reactive, but expression of the immune checkpoint receptors TIM-3, TIGIT and LAG3 is also abundant. This study represents the largest whole-genome analysis of uveal melanoma to date, and presents an updated view of the metastatic disease. © 2020, The Author(s).
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| 3. |
- Marking, Ulrika, et al.
(författare)
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Duration of SARS-CoV-2 Immune Responses Up to Six Months Following Homologous or Heterologous Primary Immunization with ChAdOx1 nCoV-19 and BNT162b2 mRNA Vaccines
- 2022
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Ingår i: Vaccines. - : MDPI AG. - 2076-393X. ; 10:3, s. 359-
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Tidskriftsartikel (refereegranskat)abstract
- Heterologous primary immunization against SARS-CoV-2 is part of applied recommendations. However, little is known about duration of immune responses after heterologous vaccine regimens. To evaluate duration of immune responses after primary vaccination with homologous adeno-vectored ChAdOx1 nCoV-19 vaccine (ChAd) or heterologous ChAd/BNT162b2 mRNA vaccine (BNT), anti-spike-IgG and SARS-CoV-2 VOC-neutralizing antibody responses were measured in 354 healthcare workers (HCW) at 2 weeks, 3 months, 5 months and 6 months after the second vaccine dose. T-cell responses were investigated using a whole blood interferon gamma (IFN-gamma) release assay 2 weeks and 3 months post second vaccine dose. Two hundred and ten HCW immunized with homologous BNT were enrolled for comparison of antibody responses. In study participants naive to SARS-CoV-2 prior to vaccination, heterologous ChAd/BNT resulted in 6-fold higher peak anti-spike IgG antibody titers compared to homologous ChAd vaccination. The half-life of antibody titers was 3.1 months (95% CI 2.8-3.6) following homologous ChAd vaccination and 1.9 months (95% CI 1.7-2.1) after heterologous vaccination, reducing the GMT difference between the groups to 3-fold 6 months post vaccination. Peak T-cell responses were stronger in ChAd/BNT vaccinees, but no significant difference was observed 3 months post vaccination. SARS-CoV-2 infection prior to vaccination resulted in substantially higher peak GMTs and IFN-gamma levels and enhanced SARS-CoV-2 specific antibody and T cell responses over time. Heterologous primary SARS-CoV-2 immunization with ChAd and BNT elicits a stronger initial immune response compared to homologous vaccination with ChAd. However, although the differences in humoral responses remain over 6 months, the difference in SARS-CoV-2 specific T cell responses are no longer significant three months after vaccination.
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| 4. |
- Midlöv, Patrik, et al.
(författare)
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PERson-centredness in hypertension management using information technology (PERHIT): a protocol for a randomised controlled trial in primary health care
- 2020
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Ingår i: Blood Pressure. - : TAYLOR & FRANCIS LTD. - 0803-7051 .- 1651-1999. ; 29:3, s. 149-156
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: For primary health care (PHC), hypertension is the number one diagnosis for planned health care visits. The treatment of high blood pressure (BP) and its consequences constitutes a substantial economic burden. In spite of efficient antihypertensive medications, a low percentage of patients reach a well-controlled BP. The PERson-centredness in Hypertension management using Information Technology (PERHIT) Study is a multicentre randomised controlled trial. PERHIT is designed to evaluate the effect of supporting self-management on systolic blood pressure by the use of information technology in Swedish primary health care. Materials and Methods: After inclusion, 900 patients from 36 PHC centres are randomised to two groups. In the intervention group, patients are provided with a self-management support system including a home-BP monitor and further requested to perform self-reports and measure BP every evening for eight consecutive weeks. In the control group, patients receive treatment as usual. Results: The primary outcome will be the change in systolic blood pressure in patients with hypertension. In addition, person-centredness, daily life activities, awareness of risk and health care costs will also be evaluated. Conclusion: The results of this randomised controlled trial with assessment of blood pressure and same-day self-reports will provide patients a tool to understand the interplay between blood pressure and lifestyle applicable to primary health care. The self-management support system may be of importance for improved adherence to treatment and persistence to treatment recommendations.
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| 5. |
- Nilsson, Klara, et al.
(författare)
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Surgical Morbidity and Mortality From the Multicenter Randomized Controlled NeoRes II Trial : Standard Versus Prolonged Time to Surgery After Neoadjuvant Chemoradiotherapy for Esophageal Cancer.
- 2020
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Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 272:5, s. 684-689
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate if prolonged TTS after completed nCRT improves postoperative outcomes for esophageal and esophagogastric junction cancer.SUMMARY OF BACKGROUND DATA: TTS has traditionally been 4-6 weeks after completed nCRT. However, the optimal timing is not known.METHODS: A multicenter clinical trial was performed with randomized allocation of TTS of 4-6 or 10-12 weeks. The primary endpoint of this sub-study was overall postoperative complications defined as Clavien-Dindo grade II-V. Secondary endpoints included complication severity according to Clavien-Dindo grade IIIb-V, postoperative 90-day mortality, and length of hospital stay. The study was registered in Clinicaltrials.gov (NCT02415101).RESULTS: In total 249 patients were randomized. There were no significant differences between standard TTS and prolonged TTS with regard to overall incidence of complications Clavien-Dindo grade II-V (63.2% vs 72.6%, P = 0.134) or regarding Clavien-Dindo grade IIIb-V complications (31.6% vs 34.9%, P = 0.603). There were no statistically significant differences between standard and prolonged TTS regarding anastomotic leak (P = 0.596), conduit necrosis (P = 0.524), chyle leak (P = 0.427), pneumonia (P = 0.548), and respiratory failure (P = 0.723). In the standard TTS arm 5 patients (4.3%) died within 90 days of surgery, compared to 4 patients (3.8%) in the prolonged TTS arm (P = 1.0). Median length of hospital stay was 15 days in the standard TTS arm and 17 days in the prolonged TTS arm (P = 0.234).CONCLUSION: The timing of surgery after completed nCRT for carcinoma of the esophagus or esophagogastric junction, is not of major importance with regard to short-term postoperative outcomes.
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| 6. |
- Ny, Lars, 1967, et al.
(författare)
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The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- The authors report the results of the phase II PEMDAC clinical study testing the combination of the HDAC inhibitor entinostat with the anti- PD-1 antibody pembrolizumab in uveal melanoma. Low tumor burden, a wildtype BAP1 gene in the tumor or iris melanoma correlates with response and longer survival. Preclinical studies have suggested that epigenetic therapy could enhance immunogenicity of cancer cells. We report the results of the PEMDAC phase 2 clinical trial (n = 29; NCT02697630) where the HDAC inhibitor entinostat was combined with the PD-1 inhibitor pembrolizumab in patients with metastatic uveal melanoma (UM). The primary endpoint was objective response rate (ORR), and was met with an ORR of 14%. The clinical benefit rate at 18 weeks was 28%, median progression free survival was 2.1 months and the median overall survival was 13.4 months. Toxicities were manageable, and there were no treatment-related deaths. Objective responses and/or prolonged survival were seen in patients with BAP1 wildtype tumors, and in one patient with an iris melanoma that exhibited a UV signature. Longer survival also correlated with low baseline ctDNA levels or LDH. In conclusion, HDAC inhibition and anti-PD1 immunotherapy results in durable responses in a subset of patients with metastatic UM.
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| 7. |
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| 8. |
- Almasoudi, Wejdan, et al.
(författare)
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Co-occurrence of CLCN2-related leukoencephalopathy and SPG56
- 2023
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Ingår i: Clinical Parkinsonism and Related Disorders. - : Elsevier BV. - 2590-1125. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Family Report: Two rare autosomal recessive neurological disorders, leukoencephalopathy with ataxia and spastic paraplegia 56 (SPG56), were found in members of the same family. Two siblings presented with spastic paraplegia, cognitive impairment, bladder and bowel dysfunction and gait ataxia; their consanguineous parents were unaffected. Ophthalmological examination revealed chorioretinopathy. Brain MRI showed T2 hyperintensities and T1 hypointensities in the internal capsules, cerebral peduncles, pyramidal tracts and middle cerebellar peduncles. Both affected siblings were homozygous for CYP2U1 c.947A > T p.(Asp316Val), a known cause for SPG56. However, they were also homozygous for the novel variant CLCN2 c.607G > T, p.(Gly203Cys), classified as a variant of unknown significance. Testing of additional family members revealed homozygosity for both variants in an additional brother, whom we initially considered unaffected. Both male CLCN2 carriers were infertile, and review of the literature revealed one reported case with azoospermia, however the brother had no overt signs of SPG56. His testicular biopsy revealed incomplete maturation arrest in spermatogenesis; clinically we found mild memory impairment and hand tremor and MRI showed similar changes as his siblings. We consider CLCN2 c.607G > T pathogenic because of the neuroradiological and clinical findings, including azoospermia. Conclusion: Considerable workup may be required to determine the pathogenicity of novel variants, and to unambiguously associate phenotype with genotype. In very rare disorders, highly specific clinical or biomarker combinations provide sufficient evidence for a variant's pathogenicity. Phenotypic variation of monogenic disorders described in the literature may be attributed to a second co-occurring monogenic disorder, especially in consanguineous families. SPG56 may have reduced penetrance.
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| 9. |
- Andersson, Ulrika, et al.
(författare)
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Associations between daily home blood pressure measurements and self-reports of lifestyle and symptoms in primary care: the PERHIT study
- 2024
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Ingår i: Scandinavian Journal of Primary Health Care. - : TAYLOR & FRANCIS LTD. - 0281-3432 .- 1502-7724.
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Tidskriftsartikel (refereegranskat)abstract
- Objective To explore in a primary care setting the associations between patients' daily self-measured blood pressure (BP) during eight weeks and concurrent self-reported values of wellbeing, lifestyle, symptoms, and medication intake. We also explore these associations for men and women separately. Design and setting The study is a secondary post-hoc analysis of the randomised controlled trial PERson-centeredness in Hypertension management using Information Technology (PERHIT). The trial was conducted in primary health care in four regions in Southern Sweden. Patients Participants (n = 454) in the intervention group in the PERHIT-trial used an interactive web-based system for self-management of hypertension for eight consecutive weeks. Each evening, participants reported in the system their wellbeing, lifestyle, symptoms, and medication adherence as well as their self-measured BP and heart rate. Main outcome measures Association between self-reported BP and 10 self-report lifestyle-related variables. Results Self-reported less stress and higher wellbeing were similarly associated with BP, with 1.0 mmHg lower systolic BP and 0.6/0.4 mmHg lower diastolic BP (p < 0.001). Adherence to medication had the greatest impact on BP levels (5.2/2.6 mmHg, p < 0.001). Restlessness and headache were also significantly associated with BP, but to a lesser extent. Physical activity was only significantly associated with BP levels for men, but not for women. Conclusion In hypertension management, it may be important to identify patients with high-stress levels and low wellbeing. The association between medication intake and BP was obvious, thus stressing the importance of medication adherence for patients with hypertension.
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| 10. |
- Andersson, Ulrika, et al.
(författare)
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Associations between daily home blood pressure measurements and self-reports of lifestyle and symptoms in primary care: the PERHIT study
- 2024
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Ingår i: SCANDINAVIAN JOURNAL OF PRIMARY HEALTH CARE. - : TAYLOR & FRANCIS LTD. - 0281-3432 .- 1502-7724.
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Tidskriftsartikel (refereegranskat)abstract
- Objective To explore in a primary care setting the associations between patients' daily self-measured blood pressure (BP) during eight weeks and concurrent self-reported values of wellbeing, lifestyle, symptoms, and medication intake. We also explore these associations for men and women separately. Design and setting The study is a secondary post-hoc analysis of the randomised controlled trial PERson-centeredness in Hypertension management using Information Technology (PERHIT). The trial was conducted in primary health care in four regions in Southern Sweden. Patients Participants (n = 454) in the intervention group in the PERHIT-trial used an interactive web-based system for self-management of hypertension for eight consecutive weeks. Each evening, participants reported in the system their wellbeing, lifestyle, symptoms, and medication adherence as well as their self-measured BP and heart rate. Main outcome measures Association between self-reported BP and 10 self-report lifestyle-related variables. Results Self-reported less stress and higher wellbeing were similarly associated with BP, with 1.0 mmHg lower systolic BP and 0.6/0.4 mmHg lower diastolic BP (p < 0.001). Adherence to medication had the greatest impact on BP levels (5.2/2.6 mmHg, p < 0.001). Restlessness and headache were also significantly associated with BP, but to a lesser extent. Physical activity was only significantly associated with BP levels for men, but not for women. Conclusion In hypertension management, it may be important to identify patients with high-stress levels and low wellbeing. The association between medication intake and BP was obvious, thus stressing the importance of medication adherence for patients with hypertension.
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