| 1. |
- Cagigi, Alberto, et al.
(författare)
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Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination
- 2021
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Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 6:22
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the presence and durability of antibodies against SARS-CoV-2 in the airways is required to provide insights into the ability of individuals to neutralize the virus locally and prevent viral spread. Here, we longitudinally assessed both systemic and airway immune responses upon SARS-CoV-2 infection in a clinically well-characterized cohort of 147 infected individuals representing the full spectrum of COVID-19 severity, from asymptomatic infection to fatal disease. In addition, we evaluated how SARS-CoV-2 vaccination influenced the antibody responses in a subset of these individuals during convalescence as compared with naive individuals. Not only systemic but also airway antibody responses correlated with the degree of COVID-19 disease severity. However, although systemic IgG levels were durable for up to 8 months, airway IgG and IgA declined significantly within 3 months. After vaccination, there was an increase in both systemic and airway antibodies, in particular IgG, often exceeding the levels found during acute disease. In contrast, naive individuals showed low airway antibodies after vaccination. In the former COVID-19 patients, airway antibody levels were significantly elevated after the boost vaccination, highlighting the importance of prime and boost vaccinations for previously infected individuals to obtain optimal mucosal protection.
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| 2. |
- Yu, Meng, et al.
(författare)
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Delayed generation of functional virus-specific circulating T follicular helper cells correlates with severe COVID-19
- 2023
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Ingår i: Nature Communications. - : NATURE PORTFOLIO. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Effective humoral immune responses require well-orchestrated B and T follicular helper (Tfh) cell interactions. Whether these interactions are impaired and associated with COVID-19 disease severity is unclear. Here, longitudinal blood samples across COVID-19 disease severity are analysed. We find that during acute infection SARS-CoV-2-specific circulating Tfh (cTfh) cells expand with disease severity. SARS-CoV-2-specific cTfh cell frequencies correlate with plasmablast frequencies and SARS-CoV-2 antibody titers, avidity and neutralization. Furthermore, cTfh cells but not other memory CD4 T cells, from severe patients better induce plasmablast differentiation and antibody production compared to cTfh cells from mild patients. However, virus-specific cTfh cell development is delayed in patients that display or later develop severe disease compared to those with mild disease, which correlates with delayed induction of high-avidity neutralizing antibodies. Our study suggests that impaired generation of functional virus-specific cTfh cells delays high-quality antibody production at an early stage, potentially enabling progression to severe disease. T follicular helper cells (Tfh) enhance antibody responses and can circulate or be resident in lymph nodes. Here the authors show that during acute SARS-CoV-2 infection, circulating Tfh cells correlate with antibody titres and plasmablast levels but in more severe COVID-19 cases, cTfh generation is delayed.
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| 3. |
- Anastasopoulou, Stavroula, et al.
(författare)
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Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia : phenotypes, risk factors and genotypes
- 2020
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Ingår i: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 107:10, s. 2318-2328
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Tidskriftsartikel (refereegranskat)abstract
- Central nervous system (CNS) toxicity is common at diagnosis and during treatment of pediatric acute lymphoblastic leukemia (ALL). We studied CNS toxicity in 1,464 children aged 1.0-17.9 years, diagnosed with ALL and treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. Genome-wide association studies, and a candidate single-nucleotide polymorphism (SNP; n=19) study were performed in 1,166 patients. Findings were validated in an independent Australian cohort of children with ALL (n=797) in whom two phenotypes were evaluated: diverse CNS toxicities (n=103) and methotrexate-related CNS toxicity (n=48). In total, 135/1,464 (9.2%) patients experienced CNS toxicity for a cumulative incidence of 8.7% (95% confidence interval: 7.31-10.20) at 12 months from diagnosis. Patients aged >= 10 years had a higher risk of CNS toxicity than had younger patients (16.3% vs. 7.4%; P < 0.001). The most common CNS toxicities were posterior reversible encephalopathy syndrome (n=52, 43 with seizures), sinus venous thrombosis (n=28, 9 with seizures), and isolated seizures (n=16). The most significant SNP identified by the genome-wide association studies did not reach genomic significance (lowest P-value: 1.11x10(-6)), but several were annotated in genes regulating neuronal functions. In candidate SNP analysis, ATXN1 rs68082256, related to epilepsy, was associated with seizures in patients < 10 years (P=0.01). ATXN1 rs68082256 was validated in the Australian cohort with diverse CNS toxicities (P=0.04). The role of ATXN1 as well as the novel SNP in neurotoxicity in pediatric ALL should be further explored.
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| 4. |
- Bakken, Anders Galaasen, et al.
(författare)
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Are changes in pain associated with changes in heart rate variability in patients treated for recurrent or persistent neck pain?
- 2022
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Ingår i: BMC Musculoskeletal Disorders. - : BMC. - 1471-2474. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPersistent or recurrent neck pain is associated with perturbations in the autonomic nervous system balance, and nociceptive stimulation has been seen to influence this balance. However, very few prospective studies have addressed the extent to which changes in pain associate with changes in autonomic cardiac regulation. Therefore, we investigated if changes in pain vary with changes in heart rate variability in a cohort of patients treated for persistent or recurrent neck pain.MethodThis analysis is based on data from a randomized controlled trial in which participants were given home stretching exercises with or without spinal manipulative therapy for two weeks. As the effectiveness of the intervention (home stretching exercises and spinal manipulative therapy) was found to be equal to the control (home stretching exercises alone), all 127 participants were studied as one cohort in this analysis. During the intervention, pain levels were recorded using daily text messages, and heart rate variability was measured in the clinics three times over two weeks. Two approaches were used to classify patients based on changes in pain intensity: 1) Clinically important changes in pain were categorized as either "improved" or "not improved" and, 2) Pain development was measured using pain trajectories, constructed in a data driven approach. The association of pain categories and trajectories with changes in heart rate variability indices over time were then analysed using linear mixed models.ResultsHeart rate variability did not differ significantly between improved and not-improved patients, nor were there any associations with the different pain trajectories.ConclusionsIn conclusion, changes in pain after home stretching exercises with or without spinal manipulative therapy over two weeks were not significantly associated with changes in heart rate variability for patients with persistent or recurrent neck pain. Future studies should rely on more frequent measurements of HRV during longer treatment periods.Trial registrationThe trial was registered at ClinicalTrials.gov, registration number: NCT03576846.
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| 5. |
- Holmlund, Lisa, et al.
(författare)
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Are psychosocial work factors and work-home interference associated with time to first full return-to-work after sick leave due to common mental disorders?
- 2023
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer. - 0340-0131 .- 1432-1246. ; 96, s. 747-755
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo (1) examine the time to first full return-to-work (RTW), and (2) investigate whether psychosocial work factors and work-home interference are associated with time to first full RTW after sick leave due to common mental disorders (CMDs).MethodsThe cohort study comprised 162 employees on sick leave due to CMDs participating in a two-armed cluster-randomised controlled trial in Sweden. Baseline data consisted of a web-based questionnaire and follow-up data of repeated text messages every fourth week for 12 months. The time to first full RTW was estimated using the Kaplan–Meier Estimator. Parametric Weibull survival models with interval-censored outcomes were used to determine associations between psychosocial work factors and work-home interference with time to first full RTW. In a post hoc analysis, time-interval differences in associations for 0– ≤ 6- versus > 6–12 months were tested.ResultsDuring the 12-month follow-up, n = 131 (80.9%) reported a first full RTW. The median time to this RTW was 16 weeks (95% CI 12; 20). High psychological job demands, high emotional job demands, high work-to-home interference (WHI), and low social job support were independently associated with a longer time to first full RTW. Time-interval differences were found for job control and emotional job demands.ConclusionsPsychosocial work demands and WHI are associated with a longer time to RTW after sick leave due to CMDs. Work organisations and rehabilitation practices should include accommodations for high psychological and emotional job demands during RTW, as well as pay attention to the risk of spill-over of high job demands into employees’ private lives.
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| 6. |
- Jarrick, Simon, 1977-, et al.
(författare)
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Immunoglobulin A nephropathy and ischemic heart disease : a nationwide population-based cohort study
- 2021
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Ingår i: BMC Nephrology. - : BioMed Central (BMC). - 1471-2369. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chronic kidney disease has been linked to cardiovascular disease and specifically ischemic heart disease (IHD), but large-scale population data in patients with immunoglobulin A nephropathy (IgAN) are missing.OBJECTIVE: To examine absolute and relative risks for IHD in patients with IgAN.METHODS: Population-based register-based cohort study in Sweden. We identified 3945 patients with biopsy-verified IgAN, and 19,272 age- and sex-matched reference individuals from the general population. To reduce residual confounding from genetic factors and early environmental factors we carried out secondary analyses, where we compared 3039 IgAN patients with 6729 siblings, whereas a spousal analysis consisted of 2377 married couples where one of the spouses had IgAN. Data on IHD and end-stage renal disease (ESRD) were retrieved from the nationwide Patient Register. Cox regression estimated hazard ratios (HRs) adjusted for matching variables, education, country of birth, cancer, diabetes mellitus, and other systemic inflammatory diseases.RESULTS: During a follow-up of 55,527 person-years (py; mean follow-up 14.1 years), 371 patients (9.4%) with IgAN developed IHD (6.7/1000 py), compared with 1070 (5.6%) in 287,677 py in reference individuals (3.7/1000 py). The corresponding adjusted HR was 1.86 (95%CI = 1.63-2.13), equivalent to one extra case of IHD per 34 IgAN patients followed-up for 10 years. HRs were similar in men and women with IgAN, but higher in the first year after diagnosis and in patients born outside the Nordic countries. Patients with IgAN were at increased risk of IHD also compared to siblings (HR = 2.07; 95%CI = 1.62-2-64) and spouses (HR = 1.91; 95%CI = 1.40-2.61).CONCLUSIONS: In this nationwide population-based study, patients with IgAN were at an 86% increased risk of future IHD.
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| 7. |
- Johansson, Fredrik, et al.
(författare)
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Eccentric and isometric shoulder rotation strength and range of motion : Normative values for adolescent competitive tennis players
- 2022
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Ingår i: Frontiers in Sports and Active Living. - : Frontiers Media SA. - 2624-9367. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this cross-sectional study was to investigate isometric internal rotation (IR), external rotation (ER), abduction (ABD), and eccentric external rotation (eccER) shoulder strength and rotational range of motion (ROM) in adolescent male and female competitive tennis players. Additional aims of the study were to provide a tennis-specific normative database based on a large sample of players to deepen the knowledge regarding shoulder strength and ROM for adolescent competitive tennis players, and to discuss differences based on sex, age, and level of play. Shoulder strength and ROM was assessed in 301 adolescent competitive tennis players, 176 boys and 125 girls with a mean age of 14.6 and 14.4 years, respectively. Outcome variables of interest were isometric IR and ER strength, ABD strength, eccER shoulder strength, intermuscular strength ratios ER/IR and eccER/IR, IR ROM, ER ROM, and total range of motion (TROM). A General Linear Model two-way ANOVA was used to analyze differences in sex, age, and level of play. The findings of this study demonstrated age, side, and sex differences in the shoulder isometric strength, the eccER strength and ROM in adolescent competitive tennis players. Furthermore, when strength was expressed as ratios ER/IR and eccER/IR both sexes showed a lower ratio for eccER/IR in national players (0.95 ± 0.22 and 0.95 ± 0.23) compared to regional players (1.01 ± 0.32 and 1.07 ± 0.29) for male and female players, respectively. In conclusion, this paper presents a tennis-specific normative database for shoulder rotation strength and ROM in adolescent male and female competitive players. The key points in this evaluation are strength values normalized to body mass, intermuscular ratios, and TROM.
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| 8. |
- Klasson, Caritha, et al.
(författare)
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Sex Differences in the Effect of Vitamin D on Fatigue in Palliative Cancer Care : A Post Hoc Analysis of the Randomized, Controlled Trial 'Palliative-D'
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- In the randomized, placebo-controlled, double-blind trial 'Palliative-D', vitamin D treatment of 4000 IE/day for 12 weeks reduced opioid use and fatigue in vitamin-D-deficient cancer patients. In screening data from this trial, lower levels of vitamin D were associated with more fatigue in men but not in women. The aim of the present study was to investigate possible sex differences in the effect of vitamin D in patients with advanced cancer, with a specific focus on fatigue. A post hoc analysis of sex differences in patients completing the Palliative-D study (n = 150) was performed. Fatigue assessed with the Edmonton Symptom Assessment Scale (ESAS) was reduced in vitamin-D-treated men; -1.50 ESAS points (95%CI -2.57 to -0.43; p = 0.007) but not in women; -0.75 (95%CI -1.85 to 0.36; p = 0.18). Fatigue measured with EORTC QLQ-C15-PAL had a borderline significant effect in men (-0.33 (95%CI -0.67 to 0.03; p = 0.05)) but not in women (p = 0.55). The effect on fatigue measured with ESAS in men remained the same after adjustment for opioid doses (p = 0.01). In conclusion, the positive effect of the correction of vitamin D deficiency on fatigue may be more pronounced in men than in women. However, studies focused on analyzing sex differences in this context must be performed before firm conclusions can be drawn.
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| 9. |
- Malin Igra, Annachiara, et al.
(författare)
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Environmental metal exposure and growth to 10 years of age in a longitudinal mother-child cohort in rural Bangladesh
- 2021
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 156
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early-life exposure to arsenic (As), cadmium (Cd), and lead (Pb) has been linked to smaller birth and early childhood anthropometry, but little is known beyond the first years in life.Objectives: To evaluate the impact of gestational and childhood exposures to As, Cd, and Pb on growth up to 10 years of age.Methods: We studied 1530 mother-child dyads from a nested sub-cohort of the MINIMat trial in rural Matlab, Bangladesh. Metal concentrations in maternal erythrocytes during pregnancy and in children's urine at 10y were measured by inductively coupled plasma mass spectroscopy. Child height and weight were measured at 19 occasions from birth until 10y and converted to height-for-age Z-scores (HAZ) and weight-for-age Z-scores (WAZ). Associations between log2-transformed metal concentrations and growth parameters were assessed with multivariable-adjusted regression models.Results: Children's concurrent urinary Cd (median 0.24 µg/L), reflecting long-term exposure, was inversely associated with WAZ (B: -0.072; 95% confidence interval (CI): -0.12, -0.020; p = 0.007), and possibly HAZ (B: -0.046; 95% CI: -0.096, 0.0014; p = 0.057), at 10y. The association with WAZ was stronger in boys than in girls. Maternal erythrocyte Cd (median 0.90 µg/kg) during pregnancy was inversely associated with WAZ during childhood only in boys (B: -0.071, 95% CI: -0.14, -0.0047, p = 0.036). Concurrent urinary Pb (median 1.6 µg/L) was inversely associated with WAZ (B: -0.084; 95% CI: -0.16, -0.0085; p = 0.029) and HAZ (B: -0.087; 95% CI: -0.15, -0.021; p = 0.010) in boys, but not in girls. Neither gestational nor childhood As exposure (median maternal erythrocyte As 4.3 µg/kg and children's urinary As 57 µg/L) was associated with growth up to 10y.Conclusions: While all effect estimates were small, environmental exposure to Cd and Pb is common and impaired growth is of public health concern, especially for children already at risk of reduced growth due to malnutrition. Gender differences in susceptibility need further investigation.
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| 10. |
- Ohm, Joel, et al.
(författare)
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Socioeconomic Disparities and Mediators for Recurrent Atherosclerotic Cardiovascular Disease Events After a First Myocardial Infarction
- 2023
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 148:3, s. 256-267
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Low socioeconomic status is associated with worse secondary prevention use and prognosis after myocardial infarction (MI). Actions for health equity improvements warrant identification of risk mediators. Therefore, we assessed mediators of the association between socioeconomic status and first recurrent atherosclerotic cardiovascular disease event (rASCVD) after MI.METHODS:In this cohort study on 1-year survivors of first-ever MI with Swedish universal health coverage ages 18 to 76 years, individual-level data from SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) and linked national registries was collected from 2006 through 2020. Exposure was socioeconomic status by disposable income quintile (principal proxy), educational level, and marital status. The primary outcome was rASCVD and secondary outcomes were cardiovascular and all-cause mortality. We initially assessed the incremental attenuation of hazard ratios with 95% CIs in sequential multivariable models adding groups of potential mediators (ie, previous risk factors, acute presentation and infarct severity, initial therapies, and secondary prevention). Thereafter, the proportion of excess rASCVD associated with a low income mediated through nonparticipation in cardiac rehabilitation, suboptimal statin management, a cardiometabolic risk profile, persistent smoking, and blood pressure above target after MI were calculated using causal mediation analysis.RESULTS:Among 68 775 participants (73.8% men), 7064 rASCVD occurred during a mean 5.7-year follow-up. Income, adjusted for age, sex, and calendar year, was associated with rASCVD (hazard ratio, 1.63 [95% CI, 1.51-1.76] in the lowest versus highest income quintile). Risk attenuated most by adjustment for previous risk factors and by adding secondary prevention variables for a final model (hazard ratio, 1.38 [95% CI, 1.26-1.51]) in the lowest versus highest income quintile. The proportions of the excess 15-year rASCVD risk in the lowest income quintile mediated through nonparticipation in cardiac rehabilitation, cardiometabolic risk profile, persistent smoking, and poor blood pressure control were 3.3% (95% CI 2.1-4.8), 3.9% (95% CI, 2.9-5.5), 15.2% (95% 9.1-25.7), and 1.0% (95% CI 0.6-1.5), respectively. Risk mediation through optimal statin management was negligible.CONCLUSIONS:Nonparticipation in cardiac rehabilitation, a cardiometabolic risk profile, and persistent smoking mediate income-dependent prognosis after MI. In the absence of randomized trials, this causal inference approach may guide decisions to improve health equity.
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