Upsala journal of medical sciences最新文献

High stroma content, as measured by tumor-stroma ratio (TSR), is generally a negative prognostic parameter for epithelial cancers, including sporadic colorectal cancer (sCRC). Inflammatory bowel disease patients have higher risk for colorectal cancer than the background population. Evidence suggests that this colitis-associated colorectal cancer (CAC) is more aggressive and occurs at younger age than sCRC. CAC also differs from sCRC in oncogenesis and prognosis. This study tests the hypothesis that TSR in CAC tumors correlates with survival. Age at CAC diagnosis relative to TSR was also explored. TSR was quantified in 36 CAC cases. In routine hematoxylin-eosin staining, the amount of stroma was estimated in categorical steps of 10% increments per image field. The area with highest amount of stroma and tumor tissue at all quadrants of the visual field boundary was scored for TSR. For statistical analysis, tumors were divided into stroma-high (> 50%) or stroma-low (≤ 50%). Of all cases, 22 were stroma-high and 14 were stroma-low. Five-year survival in the stroma-high group was 32% (n = 22), compared to 71% (n = 14) in the stroma-low group (p = 0.049). High stroma content was more frequent if cancer diagnosis was before 60 years of age (17/23) compared to after 60 years of age (5/13). Despite differences in oncogenesis and tumor biology in CAC compared to sCRC, high stroma content also predicts worse outcome in CAC and is particularly common in younger patients.

Objective: Although polymorphisms in the Toll-like receptor 2 (TLR2) gene have been proposed as host genetic factors influencing susceptibility to Helicobacter pylori infection, existing data remain inconclusive. This meta-analysis aimed to clarify whether two common variants - rs3804099 and del -196 to -174 - contribute to infection risk across diverse populations.

Materials and methods: A systematic search of PubMed, Scopus, and Web of Science (up to January 2025) identified eligible case-control studies examining the association between TLR2 polymorphisms and H. pylori infection. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity, publication bias, and sensitivity were assessed according to PRISMA 2020 guidelines.

Results: Ten studies comprising 4,521 subjects were included. Pooled analyses under allelic, dominant, recessive, homozygous, and heterozygous models revealed no significant association between either rs3804099 or del -196 to -174 polymorphisms and infection risk. Substantial inter-study heterogeneity was observed, particularly for rs3804099, but sensitivity analyses confirmed the stability of pooled results.

Conclusion: This meta-analysis refutes a consistent genetic association between TLR2 rs3804099 or del -196 to -174 polymorphisms and H. pylori infection. The findings suggest that host innate immunity variability alone does not explain differences in infection susceptibility among populations. Future studies integrating bacterial virulence genotypes and host immunogenetic profiles are warranted to delineate population-specific risk mechanisms.

Objectives: This study aimed to determine the effects of von Hippel-Lindau protein (VHL) expression on hypoxia-inducible factor (HIF) and E-cadherin proteins. Furthermore, to evaluate the influence of the VHL-HIF-E-cadherin pathway in clear cell renal cell carcinoma (ccRCC).

Materials and methods: This study used tissue samples collected from 150 patients with ccRCC and 24 adjacent kidney cortex samples. Immunoblotting was performed to measure the expression levels of VHL and E-cadherin. Additionally, nuclear expression of HIF-α was evaluated by immunohistochemistry (IHC) using a tissue microarray (TMA).

Results: pVHL levels were lower in ccRCC than in the adjacent kidney cortex; however, pVHL levels showed no correlation with clinicopathological parameters. Nuclear HIF-1α levels were higher in stage IV tumors, whereas HIF-2α levels increased with tumor size. No correlation was observed between HIF-3α levels and clinicopathological parameters. E-cadherin protein expression was reduced in ccRCC tissues and in higher-stage and larger tumors. In pVHL-high ccRCC, E-cadherin levels were lower in advanced-stage and larger tumors. Higher levels of HIF-1α and HIF-3α were observed in pVHL-low tumors. E-cadherin expression negatively correlated with nuclear HIF-1α expression. In pVHL-high ccRCCs, E-cadherin was negatively correlated with HIF-1α, while in pVHL-low ccRCCs, E-cadherin was negatively correlated with HIF-2α. E-cadherin was not associated with cancer-specific survival in patients with pVHL-low tumors, whereas E-cadherin expression was linked to improved survival in patients with pVHL-high tumors.

Conclusion: VHL inactivation causes HIF-α activation and suppresses E-cadherin expression, thereby promoting ccRCC progression. This study provides insights into the potential biomarkers and therapeutic targets for ccRCC treatment.

Patients with systemic lupus erythematosus (SLE) display an increased expression of type I interferon (IFN)-regulated genes, a so-called IFN signature. This discovery was preceded by the observation in Uppsala that patients with malignant diseases treated with type I IFN occasionally developed autoimmune diseases, including SLE. The adverse event of IFN treatment was the start of an intensive search for the role of the type I IFN system in patients with spontaneously occurring SLE. A key finding by our group was the detection in patients with SLE of endogenous IFN-inducers that could activate plasmacytoid dendritic cells (pDC) to IFN production. Further studies revealed the mechanisms by which these cells are triggered to a continuous IFN synthesis. We could also identify a large number of risk genes for SLE and several molecules connected to type I IFN production and response. My group early on suggested the possibility that some of these molecules are suitable therapeutic targets in SLE, but also other IFN-driven diseases. Antibodies against the type I IFN receptor (anifrolumab) have recently shown efficacy in clinical trials for SLE, and anifrolumab is now approved as a treatment for this disease. Several other drugs targeting critical molecules in the IFN signaling pathways - including BCDA-2 (Blood Dendritic Cell Antigen 2), TLR7/8 (Toll-like receptor 7/8), and TYK2 (Tyrosine Kinase 2) - are currently in early clinical phases, potentially expanding therapeutic options for SLE. In this review, several important observations regarding the role of the type I IFN system in SLE and therapeutic implications are discussed.

Background: Two out of three randomised controlled trials (RCTs) fail to meet their recruitment goals. Recruitment to Efficacy oF Fluoxetine - a randomisEd Controlled Trial in Stroke (EFFECTS), fluoxetine for stroke recovery was slower than anticipated. We aimed to evaluate an intervention to improve recruitment to EFFECTS.

Methods: This stepped wedge, cluster randomised study investigated whether a teleconference with the study personnel and the head of department could enhance recruitment in the ongoing EFFECTS. We included 20 low- and medium recruiting active centres. We excluded high recruiting centres. All centres started as controls and were followed by 60 days of observation. We used block randomisation. The primary outcome was a 20% increase of recruitment within 60 days post intervention compared within 60 days pre intervention. Secondary outcomes were comparing recruitment between different types of centres, that is small versus large or experienced versus non-experienced centres, and university versus non-university hospitals. In exploratory analyses, recruitment within 30 days post versus 30 days pre intervention was compared.

Results: The recruitment increased by 10% at 60 days. We noticed a short-lived increase of 23% the first month. The increased recruitment was most pronounced in low-recruiting, small and non-university hospitals. The recruitment of patients increased after the first contact with the centres where we announced that there would be a conference.

Conclusion: A teleconference with the study personnel and the head of department increased the recruitment by 23% within 30 days and by 10%, 60 days post intervention in this embedded RCT. This implies that this structured intervention aimed at increased recruitment was short-lived and would need frequent repetitions in order to be effective.

Objective: The aim of this review is to describe the regulatory background of the COVID-19 vaccines, the national recommendations for use issued and vaccine uptake in Sweden. It includes an overview of licensing and relevant safety aspects identified by the European Medicines Agency (EMA) and the national vaccination plan issued by the Public Health Agency (PHA) of Sweden.

Materials and methods: Information on dates of licensing and safety aspects of importance identified by EMA published on its website, was compiled and presented in a chronological order. National recommendations on COVID-19-vaccination and vaccinations-data on uptake and coverage using the national-vaccine-register are presented.

Results: COVID-19 vaccines development, assessments using rolling review and licensing of the covid-19 vaccines was done in 2020 during less than a year. Large-scale production was implemented. Monthly safety reviews performed by the EMA identified risk for thrombosis with thrombocytopenia syndrome with adenoviral vaccines and myocarditis for mRNA vaccines which led to restrictions in national recommendations for specified groups.National vaccinations were launched in a phased manner during 2021. Persons of high age, risk groups and nursing home personnel were prioritised during primary vaccinations and for initial boosters. In the Swedish population, 85% recieved at least on vaccine dose from the age of 12. At least two doses were recieved by 81% from age 18 and 95% from age 80.

Conclusion: Recommendations for national use adhered to relevant adverse drug reactions identified. The vaccine coverage was high. Timelines presented should be considered in follow-up studies of COVID-19-vaccines to manage possible selection bias and confounding.

Introduction: Investigating factors associated with contraceptive satisfaction is important to create a basis for tailored contraceptive counseling. In this study, we aimed to explore how sociodemographic characteristics affected women's level of satisfaction and choice of different contraceptive methods, using data collected during a randomized controlled trial (RCT) in the region Örebro County, Sweden.

Methods: This cross-sectional study utilized data from a previously conducted RCT. Eligible participants were women aged 20-40 years who sought contraceptive counseling. All women who participated in the RCT and completed a follow-up questionnaire were included in the analysis.

Results: Between February 2015 and March 2016, 1,946, participants were enrolled in the trial, with 1,198 (61.6%) completing the 2-month follow-up questionnaire. Overall, 81.3% of women reported being 'very satisfied' or 'satisfied' with their contraceptive method. Participants aged 27-40 years used long-acting reversible contraception (LARC) to a higher extent compared with those aged 20-26 years (adjusted odds ratio [aOR] 1.92, 95% confidence interval [CI] 1.44-2.56). Older age was associated with lower satisfaction (aOR 0.55, 95% CI 0.33-0.94).Participants with a body mass index (BMI) ≥ 25 more often used LARC (aOR 1.68, 95% CI 1.24-2.28) but were also more likely to report no use of contraceptives at all (aOR 1.56, 95% CI 1.01-2.43) compared with BMI < 25. The level of satisfaction tended to decrease with increasing BMI. Country of birth and educational level were not associated with satisfaction.

Conclusions: The use of LARC was more common among women with BMI ≥ 25 and older women. While BMI, education, and place of birth did not affect satisfaction, women aged 27-40 reported lower satisfaction. These findings contrast with prior studies and highlight the complex sociodemographic influences on contraception experiences.

Background: Patients, who are subjected to a patient's injury, are legally allowed a compensation for their suffering.

Aim: The negligence claims after surgical treatment of abdominal aortic aneurysms (AAA) registered in the National Swedish patient insurance company (Landstingens Ömsesidiga Försäkringsbolag [LÖF]) between 2006 and 2020 were analyzed. More than 95% of negligence claims are covered by LÖF. Special emphasis on avoidable or unavoidable injuries was made.

Material: In 15 years 17,000 abdominal aortic interventions were recorded in the Swedish vascular register (SWEDVASC), where vascular interventions in the whole country of Sweden are registered. A total of 151 negligence claims (0.9%) were reported to the insurance company. Available clinical information in the company's file of the claims was analyzed. The SWEDVASC data on AAA treatment were accessible.

Results: The number of Endovascular repair (EVAR) increased significantly, but the total number of interventions decreased. There were less claims after EVAR (0.7%) compared to open surgery (1.1%). There was an increase in avoidable injuries that were economically compensated (p = 0.02). Spinal cord ischemia and intestinal ischemia were dominating causes for claims.

Conclusion: The increase in the number of avoidable injuries should have an impact on how to train and support colleagues under education and efforts to diminish the injuries are essential. To develop methods to diminish the risk for non-avoidable complications is important.

Background: This study aimed to describe eating patterns among individuals with overweight and obesity and to investigate associations between eating patterns and anthropometric measures, including body mass index (BMI) and waist circumference, and blood pressure.

Methods: This study enrolled a cohort of adults with overweight or obesity (n = 176) participating in a clinical trial focused on weight reduction. Self-reported eating patterns were assessed as part of the trial's baseline survey. Trained study nurses conducted measurements of anthropometric indicators and blood pressure. To examine associations, statistical analyses included the application of the Mann-Whitney U-test, Fisher's exact test, the chi-squared test, and linear regression models as appropriate.

Results: The median age of the participants was 55 years (interquartile range [IQR] 12), 79% were female, and the median BMI was 33 kg/m² (IQR 5). The predominant eating pattern identified was characterized by five meals per day, including breakfast, two prepared meals, and two snacks. Among older participants (≥ 55 years), 51% reported eating two prepared meals per day as compared to 75% among the younger (P <> 0.05). A higher percentage of older participants reported consuming more than one snack per day (82% vs. 68%, P = 0.04). Additionally, older participants were more likely to rate their eating habits as 'good' compared to their younger counterparts (64% vs. 52%, P = 0.03). Women reported a higher number of eating occasions than men (> 3/day: 93% vs. 78%, P = 0.01) and a higher frequency of snacks (> 1 snack/day: 79% vs. 61%, P = 0.03). No significant associations between the number of eating occasions or number of snacks and BMI, waist circumference, or blood pressure (systolic and/or diastolic) were found in regression models when age and sex were considered.

Conclusions: Varying eating patterns were observed among adults with overweight and obesity according to age and sex. No association between eating patterns and anthropometric measures or blood pressure independent of age and sex was found.