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- Steding-Ehrenborg, K, et al.
(author)
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Hydraulic force is a novel mechanism of diastolic function that may contribute to decreased diastolic filling in HFpEF and facilitate filling in HFrEF
- 2021
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In: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 130:4, s. 993-1000
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Journal article (peer-reviewed)abstract
- It is a previously unrecognized physiological mechanism of the heart that diastolic filling occurs with the help of hydraulics. In patients with heart failure with preserved ejection fraction, atrial dilatation may cause the net hydraulic force to work against cardiac filling, thus further augmenting diastolic dysfunction. In contrast, it may work favorably in patients with dilated ventricles, as in heart failure with reduced ejection fraction.
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- Gianfrancesco, MA, et al.
(author)
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Genetic risk factors for pediatric-onset multiple sclerosis
- 2018
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In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 24:14, s. 1825-1834
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Journal article (peer-reviewed)abstract
- Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology. Objective: We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS. Methods: Cases with onset <18 years ( n = 569) and controls ( n = 16,251) were included from the United States and Sweden. Adjusted logistic regression and meta-analyses were performed for individual risk variants and a weighted genetic risk score (wGRS) for non-MHC variants. Results were compared to adult MS cases ( n = 7588). Results: HLA–DRB1*15:01 was strongly associated with POMS (odds ratio (OR)meta = 2.95, p < 2.0 × 10−16). Furthermore, 28 of 104 non-MHC variants studied (23%) were associated ( p < 0.05); POMS cases carried, on average, a higher burden of these 28 variants compared to adults (ORavg = 1.24 vs 1.13, respectively), though the difference was not significant. The wGRS was strongly associated with POMS (ORmeta = 2.77, 95% confidence interval: 2.33, 3.32, p < 2.0 × 10−16) and higher, on average, when compared to adult cases. Additional class III risk variants in the MHC region associated with POMS were revealed after accounting for HLA–DRB1*15:01 and HLA–A*02. Conclusion: Pediatric and adult MS share many genetic variants suggesting similar biological processes are present. MHC variants beyond HLA–DRB1*15:01 and HLA–A*02 are also associated with POMS.
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- Ekstrom, W., et al.
(author)
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Health related quality of life, reoperation rate and function in patients with diabetes mellitus and hip fracture-A 2 year follow-up study
- 2013
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In: Injury. - : Elsevier BV. - 0020-1383 .- 1879-0267. ; 44:6, s. 769-775
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Journal article (peer-reviewed)abstract
- Introduction: Diabetes mellitus confers an increased risk of hip fractures. There is a limited knowledge of how the outcome after a hip fracture in patients with diabetes affect Health Related Quality of Life (HRQoL). The primary aim of this study was to evaluate HRQoL. Secondary aims were reoperation rate, complications and functions in patients with diabetes followed for 2 years after a hip fracture. Materials and methods: Out of 2133 patients diabetes was present in 234 patients (11%). Main outcome measurements were HRQoL evaluated with EuroQoL 5-D-index score, reoperation rate, surgical and medical complications, function as walking ability, daily activities, living condition and pain. Results: Preoperatively, patients with diabetes mellitus had more pain (p = 0.044), co-morbidities, reduced health status (p = 0.001) and more often used a walking frame (p = 0.014) than patients without diabetes, whereas Katz ADL index, cognition and body mass index did not differ. There was no difference in fracture type, surgical method or reoperation between the two groups or between patients with insulin treated or oral treated diabetes. The EQ-5D(index) score decreased from 0.64 at admission to 0.45 at 4 months, 0.49 at 12 months and 0.51 at 24 months with similar results for patients with and without diabetes. During the first postoperative year there was not more medical complications among patients with diabetes, however cardiac (p = 0.023) and renal failure (p = 0.032) were more frequent in patients with diabetes at 24 months. Patients with diabetes more often had severe hip pain at 4 months (p = 0.031). At 12 months more diabetic patients were living independently (p = 0.034). There was no difference in walking ability, ADL and living condition between the groups at 24 months. Conclusion: The findings of this study indicate that patients with diabetes mellitus had more pain, co-morbidities, reduced health status preoperatively than patients without diabetes. Hip fracture patients with diabetes mellitus have more hip pain at 4 months. Cardiac and renal failure was more frequent in patients with diabetes at 24 months but otherwise we found a comparable re-operation rate, function and deterioration of Health Related Quality of Life as patients without diabetes within 2 years after a hip fracture.
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- Ellis, M, et al.
(author)
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Assessment of the clinical utility of serial beta-D-glucan concentrations in patients with persistent neutropenic fever
- 2008
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In: Journal of medical microbiology. - : Microbiology Society. - 0022-2615 .- 1473-5644. ; 57:3Pt 3, s. 287-295
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Journal article (peer-reviewed)abstract
- The performance of the Fungitell assay was investigated in 100 patients with haematological malignancy undergoing chemotherapy who developed antibiotic-unresponsive neutropenic fever (AUNF). Serum β-d-glucan (BG) concentrations were significantly elevated on the first day of AUNF and all subsequent alternate days to day 10 in 38 patients who developed an invasive fungal infection (IFI) compared to 42 patients remaining free of such infections. The mean and median values of BG were 171.9±29.6 and 95.8 pg ml−1, respectively, for patients with IFI and 64.4±17.1 and 32.9 pg ml−1 for patients with only AUNF (P<0.0001). The differences remained significant over the 10 days despite antifungal therapy. The occurrence of ≥2 sequential concentrations of ≥80 pg ml−1 (‘positive’ test) was found to give the best overall option for diagnosis, with an accuracy of 81.3 %, sensitivity of 86.8 %, positive predictive value of 76.7 % and negative predictive value of 86.5 %. Of the patients with an IFI, 78 % developed a positive test at or before the clinical diagnosis was made – this occurred at a mean (range) of 1.25 (−14 to +14) days prior to the IFI diagnosis. By starting sampling of blood from the first day of neutropenia rather than from the first day of AUNF, 50 % of the patients with subsequent IFI would have been identified 5 days earlier. Increasing sampling to daily from alternate-day frequency did not further improve this earlier timing of an IFI diagnosis. A greater proportion of patients with persistent high levels of BG without overt IFI had severe enterocyte damage or mucositis than those with lower levels of BG without IFI (P=0.002). If the results of the initial BG test had been acted on to change antifungal therapy, discontinuation would have been inappropriate in 30 % of patients and would have delayed definitive antifungal therapy. Although the findings for the cohort of patients studied are very useful, there is inter-patient variability in the test's performance. An holistic diagnostic approach is therefore necessary to interpret the test results optimally. Future studies should address this in further detail as well as the impact of empirical antifungal drug use and patient outcome.
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- Henriksson, S, et al.
(author)
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The scaffold protein WRAP53β orchestrates the ubiquitin response critical for DNA double-strand break repair
- 2014
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In: Genes & development. - : Cold Spring Harbor Laboratory. - 1549-5477 .- 0890-9369. ; 28:24, s. 2726-2738
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Journal article (peer-reviewed)abstract
- The WD40 domain-containing protein WRAP53β (WD40 encoding RNA antisense to p53; also referred to as WDR79/TCAB1) controls trafficking of splicing factors and the telomerase enzyme to Cajal bodies, and its functional loss has been linked to carcinogenesis, premature aging, and neurodegeneration. Here, we identify WRAP53β as an essential regulator of DNA double-strand break (DSB) repair. WRAP53β rapidly localizes to DSBs in an ATM-, H2AX-, and MDC1-dependent manner. We show that WRAP53β targets the E3 ligase RNF8 to DNA lesions by facilitating the interaction between RNF8 and its upstream partner, MDC1, in response to DNA damage. Simultaneous binding of MDC1 and RNF8 to the highly conserved WD40 scaffold domain of WRAP53β facilitates their interaction and accumulation of RNF8 at DSBs. In this manner, WRAP53β controls proper ubiquitylation at DNA damage sites and the downstream assembly of 53BP1, BRCA1, and RAD51. Furthermore, we reveal that knockdown of WRAP53β impairs DSB repair by both homologous recombination (HR) and nonhomologous end-joining (NHEJ), causes accumulation of spontaneous DNA breaks, and delays recovery from radiation-induced cell cycle arrest. Our findings establish WRAP53β as a novel regulator of DSB repair by providing a scaffold for DNA repair factors.
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- Bergh, Håkan, 1958, et al.
(author)
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Persistence and stability of sublingual varices over time and their connection to underlying factors: an 8 year follow up study
- 2022
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In: Bmc Oral Health. - : Springer Science and Business Media LLC. - 1472-6831. ; 22:1
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Journal article (peer-reviewed)abstract
- Objective To investigate whether sublingual varices are constant or inconstant over time and whether this is connected to background variables, cardiovascular risk factors or disease. Design This longitudinal observational study was performed between 2010 and 2020 at the Public Dental Services Vastra Vall, Varberg, Sweden. The study was based on 431 patients included in a previous study in which the relationship between sublingual varices and hypertension was examined. In connection to the annual dental examination, 281 patients were included in the follow-up study. They completed a questionnaire about background and health factors and diseases. Length and weight were measured. Two intraoral photos were taken with a digital camera. Two dentists independent of each other graded all photographs as none/few visible sublingual varices (nSV) or medium/severe sublingual varices (SV). Results The prevalence of SV was 25.6% at baseline and 30.6% at follow-up. At the follow up, a total of 76.5% had maintained their sublingual vascular status. Of those with nSV at baseline (n209), 80.9% still had nSV, and 19.1% had developed SV during the 8-year follow-up period. Of those 72 participants who had SV at baseline, 46 (63.9%) were unchanged at follow-up, and 26 (36.1%) were classified as nSV. Those who had developed SV at follow-up had a higher mean age (p = 0.003) and a higher prevalence of cardiovascular disease (CVD), 13.2% versus 3.0% (p = 0.021). This association with CVD did not persist after an adjustment for sex and age (OR 3.2, 95% CI 0.81-12.46). They exhibited more hypertension (35.0% vs. 22.5%) and diabetes type 2 (7.5% vs. 3.0%), but with no significant difference. Conclusions This study revealed that 76.5% of the participants had an unchanged status regarding sublingual varices during an 8-year period and that the development from nSV to SV was associated with advanced age.
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- Bergh, Håkan, 1958, et al.
(author)
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The Association Between Sublingual Varices and Cardiovascular Risk Factors
- 2022
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In: Vascular Health and Risk Management. - 1176-6344. ; 18, s. 319-327
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Journal article (peer-reviewed)abstract
- Objective: To study the association between sublingual varices (SV) and cardiovascular (CVD) risk factors. Methods: A total of 989 consecutive dental patients aged 55-84 years participated in the study, which applied a survey about risk factors, diseases and medications. Digital photos of the lateral borders of the tongue, height, weight, waist, hip and blood pressure were registered, and blood samples were analyzed. Those with SV were compared with those without SV (nSV). Results: Those with SV had more hypertension 41.8% vs 27.0% (p<0.0001), a higher systolic blood pressure (BP) 139.5 (SD 18.6) mmHg vs 134.3 (SD 18.8) mmHg (95% CI -7.73 - -2.72), more diabetes type 2 (DM-2) 7.4% vs 3.8% (p=0.014), a higher fasting plasma glucose 5.9 (SD 1.5) mmol/L vs 5.7 (SD 1.0) mmol/L (95% CI -0.42 - -0.05), more dyslipidemia 24.1% vs 17.7% (p=0.018), lower HDL 1.6 vs 1.7 (p=0.003), a greater waist circumference 97.0 cm vs 93.9 cm (95% CI -4.66 - -1.46), a greater waist/hip ratio 0.92 cm/cm vs 0.90 cm/cm (95% CI -0.03 - -0.01), and a higher BMI 26.6 kg/m(2) vs 26.0 kg/m(2) (95% CI -1.11 - -0.03). The following associations with SV were found in multivariate analysis: hypertension OR=1.6 (95% CI 1.19 -2.13), a high systolic BP OR =1.5 (95% CI 1.11 -2.13), a high tP-glucose OR= 1.8 (95% CI 1.03 -3.21), a low HDL OR= 1.8 (95% CI 1.15 -2.92), a greater waist circumference OR= 1.68 (95% CI 1.10 -2.58), a greater waist/hip ratio OR=2.21 (95% CI 1.36 -3.58), and a higher HMI OR=1.05 (95% CI 1.02 -1.09). Conclusion: This study shows an association between SV and a high BP, a high fP-glucose, hypertension, diabetes mellitus type 2, dyslipidemia, abdominal obesity, older age and smoking.
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- Ek, S, et al.
(author)
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Internal fixation or hip replacement for undisplaced femoral neck fractures? Pre-fracture health differences reflect survival and functional outcome
- 2022
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In: Acta orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 93, s. 643-651
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Journal article (peer-reviewed)abstract
- Background and purpose: Internal fixation (IF) has been the standard procedure for undisplaced femoral neck fractures (FNFs). However, there is a changing trend towards hip replacement (HR). Yet there is a knowledge gap regarding the benefits of this surgical method. We investigated functional outcomes in patients ≥ 70 years following HR compared to IF for undisplaced FNFs.Patients and methods: Patients ≥ 70 years with undisplaced FNF registered in the Swedish National Hip Fracture Registry (SHR) who underwent either IF or HR (hemiarthroplasty [HA)] or total hip arthroplasty [THA]) were investigated in terms of 1-year survival and proportion of reoperation. In a subsample with 4-month follow-up data (n = 3,623), pain, changes in living status, and physical function were additionally analyzed.Results: 7,758 patients were included with a mean age of 85 years. 93% of the patients were operated on with IF, 5% with HA, and 2% with THA. Patients with THA more often lived independently and were able to walk outdoors, both before and after the hip fracture. The IF and HA groups were similar in baseline characteristics, and in functional and survival outcomes. The THA group had a 54% lower adjusted risk of 1-year mortality. The proportion of reoperations within 1 year was 9.5% for IF, 5.3% for HA, and 7% for THA.Interpretation: The pre-fracture difference in health and function between patients operated on with IF, HA, and THA maked it difficult to compare outcomes of the 2 methods. Decision on surgical method must be taken on an individual level, considering patients’ well-being and allocation of resources.
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- Grondal, L, et al.
(author)
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Arthrodesis compared to Mayo resection of the first metatarsophalangeal joint in total rheumatoid forefoot reconstruction
- 2005
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In: Foot & ankle international. - : SAGE Publications. - 1071-1007 .- 1944-7876. ; 26:2, s. 135-139
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Journal article (peer-reviewed)abstract
- Background: Painful forefoot deformity from rheumatoid arthritis can be treated with resection of the lesser metatarsal heads combined with either resection or arthrodesis of the first metatarsophalangeal (MTP) joint. Methods: In a prospective, randomized study we compared arthrodesis of first MTP joint with Mayo resection as part of total forefoot reconstruction in patients with painful forefoot deformity from rheumatoid arthritis. The lesser metatarsal heads were resected and extensor tenotomy was done in all patients. Thirty-one patients were randomized to either the arthrodesis or resection group. Results: After a mean followup of 36 (26 to 52) months, the median subjective satisfaction score was 96 points out of 100 in the resection group and 92 points in the arthrodesis group. Significant improvements in pain, handicap, and activity according to Foot Function Index (FFI) were found in both groups ( p < 0.001 except for handicap in resection group and activity in fusion group were p = 0.02). There were no statistically significant differences between the groups in these measures, nor in the patients' willingness to have the procedure again. There were no recurrences of prominences or tenderness under the forefoot in either group and no recurrence of severe hallux valgus in the resection group. The arthrodeses healed in 93%. There was no higher risk for clinically relevant IP joint symptoms after arthrodesis. The operating time was significantly longer in the arthrodesis group but this was not linked to a higher wound infection rate. Conclusion: These results indicate that Mayo resection may still be a good choice for the first MTP joint in total forefoot reconstruction in patients with rheumatoid arthritis.
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- Hedstrom, AK, et al.
(author)
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Exposure to environmental tobacco smoke is associated with increased risk for multiple sclerosis
- 2011
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In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 17:7, s. 788-793
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Journal article (peer-reviewed)abstract
- Background: Tobacco smoking has consistently been associated with increased risk for multiple sclerosis. However, data has been inconsistent regarding the influence of passive smoking. Objective: The aim was to estimate the influence of passive smoking on the risk for multiple sclerosis. Methods: A population-based case–control study using incident cases of multiple sclerosis was performed in Sweden, and the study population was restricted to subjects who had never smoked (695 cases, 1635 controls). The incidence of multiple sclerosis among never-smokers who had been exposed to passive smoking was compared with that of never-smokers who had never been exposed by calculating the odds ratio with a 95% confidence interval employing logistic regression. Results: The risk for multiple sclerosis was increased among never-smokers who had been exposed to passive smoking (OR 1.3, 95% CI 1.1–1.6) compared to never-smokers who had never been exposed. The risk increased with increasing duration of exposure ( p = 0.003). Conclusions: Exposure to environmental tobacco smoke is associated with an increased risk for multiple sclerosis. Since smoking, but not usage of oral tobacco in the form of moist snuff, is associated with increased risk for multiple sclerosis, we consider that the critical effects of passive smoking may be the result of irritations in the lungs. Hence, further studies would be valuable in order to clarify whether other forms of lung irritation, such as air pollution, contribute to the triggering of multiple sclerosis.
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