Upsala journal of medical sciences最新文献

Purpose: To compare best corrected visual acuity (BCVA) measurements obtained using a digital visual acuity chart with those from the gold-standard Early Treatment Diabetic Retinopathy Study (ETDRS) chart and to assess differences in measurement variability and examination time.

Methods: Altogether 42 subjects (≥ 55 years) were examined using both charts on two separate occasions. BCVA was recorded in logMAR. Examination time was recorded. Subjects were stratified into four visual acuity classes. A nested analysis of variance (ANOVA) was used to analyze systematic differences and variance components.

Results: A statistically significant difference in BCVA between the charts was found, but the 95% confidence interval (CI) for the mean difference (Digital - ETDRS: -0.03 ± 0.04 logMAR) was below the 0.1 logMAR resolution threshold. No significant interaction was observed between chart type and acuity class. The digital chart significantly reduced examination time by an average of 50 sec (95% CI: ±21). Variance was highest between testing occasions compared with that between-subject and for interaction between chart type and subjects.

Conclusions: The digital chart provides clinically equivalent BCVA estimates compared to the ETDRS chart, with shorter examination time. Its use in routine clinical settings is supported.

Objective: This research aims to identify the main influencing factors for dysplasia in ulcerative colitis (UC) patients and explored the correlation between dysplasia and the recurrence frequency of UC.

Methods: This study retrospectively included 348 UC patients from the outpatient clinic of the Second Hospital of Hebei Medical University between December 2021 and December 2023 as the research subjects. The UC patients were divided into the dysplasia group and the non-dysplasia group based on pathological results. The general data and clinical data of the two groups were compared, and the typical computed tomography enterography (CTE) imaging features of the patients in the dysplasia group were explored. The main influencing factors for the occurrence of dysplasia in patients were screened using the univariate logistic regression analysis method and the ridge regression analysis method. All the follow-up data of the research subjects were complete, the recurrence situations of UC in the two groups were compared. The correlation between dysplasia and the recurrence frequency of UC was analysed using the Spearman rank correlation coefficient.

Results: This study found that there were statistically significant differences in indicators such as disease classification, disease severity, lesion extent, disease activity degree, and faecal calprotectin (FC) level between the two groups of patients. Patients with dysplasia presented usually with CTE imaging features of mesenteric lymphadenopathy, mucosal abnormal enhancement, and bowel wall thickening. Univariate logistic regression revealed that the above indicators were influencing factors for dysplasia in UC patients (P < 0.05). Collinearity test and ridge regression analysis showed that chronic continuous type/acute fulminant type disease classification, severe disease severity, E3 lesion range, moderately active stage/severely active stage of disease activity degree, and high FC level would increase the possibility of dysplasia (P < 0.05). The recurrence rate of UC diseases in the dysplasia group was higher than that in the non-dysplasia group, and recurrence types were also different (P < 0.05). Spearman rank correlation analysis indicated that the grade of dysplasia, disease severity, lesion range, and degree of disease activity were positively correlated with recurrence frequency of UC (P < 0.05).

Conclusion: Disease classification, disease severity, lesion extent, disease activity degree, and FC were independently correlated with occurrence of dysplasia in UC patients. Moreover, dysplasia increased the probability of patient recurrence. The grade of dysplasia and related influencing factors showed a positive correlation with the recurrence frequency of UC.

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.