UPSALA JOURNAL OF MEDICAL SCIENCES

Novel diagnostics for improved treatment of gynecological cancer
Gyllensten U
This paper summarizes the efforts to develop novel biomarkers for diagnosis and screening of the three main gynecological cancers, cervical, endometrial, and ovarian cancer, with an emphasis on research performed during the last 20 years in Uppsala. A cervical cancer screening program has existed in Sweden since 1966 using cytology as the primary test. Over the last two decades, research has provided the scientific base for a transition to self-sampling to improve convenience of the woman and achieve higher population coverage, and use of human papillomavirus as the primary test. Also, efficient prophylactic vaccines and more efficient treatment strategies of women with cervical dysplasia have been introduced. Together, these medical tools have the potential to eradicate cervical cancer by 2120, as envisaged by WHO. By contrast, efficient biomarkers for endometrial and ovarian cancer are still lacking. Through the use of high-throughput proteomics, we have identified novel plasma protein biomarkers to be used in the diagnosis of women with adnexal ovarian mass upon transvaginal ultrasound, and possibly also for early detection in population screening. Similarly, novel biomarkers for the diagnosis of endometrial cancer are being evaluated. To establish a population-based screening program requires careful cost-benefit analyses. One alternative would be to broaden the focus of the current cervical cancer screening program to include also the novel biomarkers for ovarian and endometrial cancer, and thereby achieve screening for all three gynecological cancers. A program that screens for all three diseases could increase motivation to participate and thereby population coverage.
Evaluation of drug delivery vehicles for improved transduction of oncolytic adenoviruses in solid tumor tissue
Yngve E, Ingvast S, Korsgren O and Yu D
Oncolytic viruses are promising tools for immune stimulatory gene therapy of cancer, but their clinical effect on solid tumors have so far been limited. Transduction of the target tumor cells is limited by both extracellular matrix that blocks viral spread within the solid tumor tissue and electrostatic forces that inhibit virus from binding its entry receptor on the cell surface. The enzymes and and the polycations diethylaminoethyl (, and have previously shown potential to improve gene transfer in different forms of viral gene therapy, since they may help the virus to overcome these barriers. In this study, we compared the transduction-enhancing potential of these substances when used as vehicles for adenoviral transduction in solid tumor tissue.
CORRIGENDUM
[This corrects the article DOI: 10.48101/ujms.v129.10741.].
Cost-effectiveness analysis of transcatheter aortic valve implantation versus surgical aortic valve replacement in patients with severe aortic stenosis at low risk of surgical mortality in Sweden
Nilsson K, James S, Angerås O, Backes J, Bjursten H, Candolfi P, Götberg M, Hagström H, Malmberg C, Nielsen NE, Sarmah A, Settergren M and Bromilow T
Transcatheter aortic valve implantation (TAVI) has shown similar or improved clinical outcomes compared with surgical aortic valve replacement (SAVR) in patients with symptomatic severe aortic stenosis at low risk for surgical mortality. This cost-utility analysis compared TAVI with SAPIEN 3 versus SAVR in symptomatic severe aortic stenosis patients at low risk of surgical mortality from the perspective of the Swedish healthcare system.
Cost-effectiveness analysis of transcatheter aortic valve implantation versus surgical aortic valve replacement in patients with severe aortic stenosis at low risk of surgical mortality in Sweden
Nilsson K, James S, Angerås O, Backes J, Bjursten H, Candolfi P, Götberg M, Hagström H, Malmberg C, Nielsen NE, Sarmah A, Settergren M and Bromilow T
Transcatheter aortic valve implantation (TAVI) has shown similar or improved clinical outcomes compared with surgical aortic valve replacement (SAVR) in patients with symptomatic severe aortic stenosis at low risk for surgical mortality. This cost-utility analysis compared TAVI with SAPIEN 3 versus SAVR in symptomatic severe aortic stenosis patients at low risk of surgical mortality from the perspective of the Swedish healthcare system.
Risk assessment for vaccination programmes in a pandemic. A Swedish model for efficacy and safety during COVID-19
Wikstöm G and Welsh M
ARDS severity in COVID-19: a case-control study of laboratory biomarkers and IL-10 SNP analysis
Smail SW, Albarzinji N, Karim KJ, Salih RH and Janson C
Acute respiratory distress syndrome (ARDS), which is often observed in severe cases of coronavirus disease 2019 (COVID-19), is known to be a major contributor to higher mortality rates. This study assesses how hematological parameters, inflammatory biomarkers, cytokines, and the -1,082 A/G polymorphism are associated with ARDS severity in COVID-19 patients.
The association between TNF-receptors (TNFR1 and TNFR2) and mortality as well as kidney function decline in patients with chronic kidney disease
Wändell P, Feldreich T, Larsson A, Kalra PA, Ärnlöv J, Ruge T and Carlsson AC
Higher circulating levels of tumor necrosis factor (TNF) alpha receptors 1 (TNFR1) and 2 (TNFR2) are associated with increased long-term mortality and impaired kidney function.
Avoidable injuries after intervention for abdominal aortic aneurysm: An analysis of negligence claims over 15 years in Sweden
Bergqvist D, Gustafson P and Hafström L
Patients, who are subjected to a patient's injury, are legally allowed a compensation for their suffering.
Contraceptive choices and satisfaction: a cross-sectional analysis of sociodemographic influences
Åkesson M, Brynhildsen J, Tydén T, Envall N, Backman H and Skogsdal Y
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.
Toll-like receptor 4 (TLR-4) polymorphisms and asthma risk in rural and urban settings: findings from the UK biobank
Kisiel MA, Rask-Andersen M, Johansson Å, Ek WE and Rask-Andersen A
The risk of asthma and its phenotypes may be modified by gene-environmental interactions. The previous studies on the interactions between genetic variations in the toll like 4 (TLR4) the main receptor for bacterial endotoxin, and asthma were contradictory as they were underpowered and did not consider different asthma phenotypes. The main aim of this study was to identify interactions between two single nucleotide polymorphisms (SNPs) within the gene, Asp299Gly and Thr399Ile, and residential area (urban or rural) in females and males with asthma and different asthma phenotypes.
Eating patterns in relation to anthropometrics and blood pressure among adults with overweight and obesity - a cross-sectional study
Siurua E, Alle KÅ, Bergenholtz M, Lendahls L and Holmberg S
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.
Overview of approved COVID-19 vaccines in the EU, recommendations for use in Sweden and vaccine uptake over time: Report from the Swedish Medical Products Agency and the Public Health Agency of Sweden
Zethelius B, Rubin J, Pihlström N, Liminga UW, Back H, Aronsson B, Tegnell A, Marking U, Ludvigsson JF, Andersson S and Ljung R
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.
Determinants of growth differentiation factor 15 plasma levels in outpatients with peripheral arterial disease
Skau E, Wagner P, Leppert J, Ärnlöv J and Hedberg P
Growth differentiation factor 15 (GDF-15) is a robust prognostic biomarker in patients with cardiovascular (CV) disease, and a better understanding of its clinical determinants is desirable. We aimed to study the associations between GDF-15 levels and in outpatients with peripheral arterial disease (PAD).
Elevated levels of aquaporin-4-containing extracellular vesicles in cerebrospinal fluid of patients with bipolar disorder
Wetterberg L, Mobarrez F, Nybom R, Wallén H, Pelanis A, von Rosen D and Landén M
To examine a hypothetical dysfunction of the brain water channels in bipolar disorder by analyzing aquaporin-4 (AQP4) exposing extracellular vesicles (EVs) in cerebrospinal fluid (CSF) from individuals with bipolar disorder types 1 and 2, and healthy controls.
Special issue: frontiers in recent advances on cancer diagnosis and treatment
Westermark B and Heldin CH
Associations of lower values of peak oxygen uptake and handgrip strength with a smaller liver volume
Naeem M, Markus MRP, Bahls M, Mousa M, Dörr M, Kühn JP, Bülow R, Felix SB, Targher G, Stubbe B, Ewert R, Völzke H and Ittermann T
The associations between physical fitness markers and liver volume in the general population are unclear. We investigated the associations of peak oxygen uptake (VO)and handgrip strength with liver volume in a general population sample.
From early methods for DNA diagnostics to genomes and epigenomes at high resolution during four decades - a personal perspective
Syvänen AC
In the 1980s, my research career begun with microbial DNA diagnostics at Orion Pharmaceutica in Helsinki, Finland, where I was part of an innovative team that developed novel methods based on the polymerase chain reaction (PCR) and the biotin-avidin interaction. One of our key achievements during this time was the invention of the solid-phase minisequencing method for genotyping single nucleotide polymorphisms (SNPs). In the 1990s, I shifted focus to human genetics, investigating mutations of the 'Finnish disease heritage'. During this period, I also developed quantitative methods using PCR and minisequencing of mitochondrial mutations and for forensic analyses. In the late 1990s and early 2000s, microarray-based SNP genotyping became a major topic for my research, first in Helsinki and later with my research group at Uppsala University in Sweden. By the mid-2000s, I began collaborating with leading clinicians on genetics of autoimmune disease, specifically systemic lupus erythematosus and later worked on the classification and clinical outcome of pediatric acute lymphoblastic leukemia, when large-scale genomics and epigenomics emerged. These collaborations, which focused on integrating genomics into clinical practice, lasted almost two decades until I retired from research in 2022. In parallel with my research activities, I led the SNP/DNA Technology Platform in the Wallenberg Consortium North program from 2001 to 2006. I continued as Director of the SNP&SEQ Technology Platform, which expanded rapidly during the 2010s, and became part of Science for Life Laboratory in 2013. Today (in 2024), the SNP&SEQ Technology Platform is one of the largest units of the Swedish National Genomics Infrastructure hosted by SciLifeLab. The present article provides a personal perspective on nearly four decades of research, highlighting projects and methods I found particularly exciting or important.
Transcatheter aortic valve implantation in Uppsala University Hospital 2009-2023: outcomes and temporal trends
de Wilde E, Olivetti L, James S, Christersson C, Buccheri S, Lindblom R, Amin A and Sarno G
In recent years, transcatheter aortic valve implantation (TAVI) has rapidly emerged as a key treatment option for aortic stenosis. TAVI has been performed at Uppsala University Hospital since 2009. Data on TAVI procedures have been collected in a nation-wide all-comer registry, the Swedish Transcatheter Cardiac Intervention Registry (SWENTRY). However, only limited analysis has been conducted on trends in short- and long-term outcomes of TAVI patients in Sweden.
Validity of prenatal AUDIT screening for alcohol disorders - a Nationwide Swedish register study
Hesselman S, Asp J, Pellas U, Lager S and Wikman A
This study aims to assess the external validity of the Alcohol Use Disorders Identification Test (AUDIT) in Swedish prenatal care as an indicator for alcohol-addiction disorders, and to characterize women with mismatched information in healthcare registers.
Enhancing Recruitment Using Teleconference and Commitment Contract (ERUTECC): a stepped wedge cluster randomised trial within the EFFECTS trial
Isaksson E, Näsman P, Wester P, Laska AC and Lundström E
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.