Kuopio University Hospital

Cardiac organ damage (OD) is associated with increased risk of cardiovascular disease. However, limited knowledge exists on cardiac OD in young patients with cryptogenic ischaemic stroke (CIS). To explore prevalence and covariates of cardiac OD in patients with CIS compared to controls participating in the SECRETO study. We analysed data from 427 patients with CIS aged <50 years and 361 age- and sex-matched controls. OD was defined as presence of abnormal left ventricular (LV) geometry (LV hypertrophy or concentric remodelling) or left atrial enlargement (LAE) assessed by echocardiography, using sex-specific threshold values. Compared to controls, patients had higher prevalences of obesity and tobacco smoking, patent foramen ovale (PFO) (52% vs. 25%) and abnormal LV geometry (12% vs. 7%, all p < 0.01), while presence of LAE did not differ. In multivariable analyses, CIS was associated with presence of abnormal LV geometry (odds ratio 1.86 [95% confidence interval 1.09-3.20], p=0.024). In separate multivariable analyses in patients only, obesity was associated with both abnormal LV geometry and LAE (both p < 0.01), and higher systolic blood pressure only with presence of abnormal LV geometry (p < 0.001). No significant association with PFO was found. In young patients with CIS participating in the SECRETO study, abnormal LV geometry was more prevalent compared to age- and sex-matched controls and associated with presence of higher blood pressure and obesity. The results point to the importance of blood pressure and weight control in CIS to prevent progression of cardiac OD and recurrent cardiovascular events.

Cancer therapies place an increasing financial burden on societies. In metastatic colorectal cancer (mCRC), an optimised curative-intent treatment combines metastasectomy, local ablative therapy, and perioperative systemic anti-cancer therapy (SACT) under multidisciplinary team guidance. The resource-intensive operative treatment strategy results in better survival than a non-operative approach with SACT only. The cost-effectiveness of the strategy including operative treatment has not been investigated in the era of modern treatment options. Patient/material and methods: A Markov model was developed to estimate lifetime healthcare costs and quality-adjusted life-years (QALYs). Patients receiving operative treatment, including metastasectomy along with SACT, and those receiving non-operative treatment with SACT only, were identified from the prospective Finnish RAXO study that recruited 1,086 patients between 2012 and 2018. Cost-effectiveness analyses and sensitivity analyses were conducted from the healthcare payer's perspective using 2023 cost levels. The mean lifetime costs (158,309€) for patients with an operative treatment produced 6.57 life years and 5.91 QALYs according to the Markov model. The non-operative treatment group had costs of 77,182€, producing 1.99 life years and 1.74 QALYs. The incremental cost-effectiveness ratio (ICER) was 19,455€/QALY, with the caveat that more favourable characteristics were present in the operative group. In probabilistic sensitivity analyses with a willingness-to-pay threshold of 30,000€/QALY, the operative treatment group had an 81% probability of being cost-effective. The results were robust in adjusted sensitivity analyses, including propensity score matched subgroups. An operative treatment strategy is cost-effective at a commonly referenced acceptability threshold.

Objective To study multidimensional factors affecting long-term mortality and causes of death in patients with systemic lupus erythematosus (SLE). Method A cohort of 224 SLE patients from the Helsinki University Hospital was established in the early 2000s. Personal interviews, examinations, and chart reviews followed a protocol that included demographics, clinical data, education, socioeconomic factors, lifestyle, and laboratory tests. Causes of death were obtained from the official death certificate statistics of Statistics Finland. Results The mean age of the patients was 47.4 years, and the median follow-up duration was 20.5 years. Eighty-two patients (36.6%) had died. Survival rates at 5, 10, and 20 years were 94.8%, 85.3%, and 63.1%, respectively. The overall standardized mortality ratio was 2.73 (95% confidence interval 2.20–3.39). In univariate analyses, baseline factors associated with mortality included age, disease duration, body mass index (BMI), education, income, damage score, comorbidities, renal failure, and smoking history. In multivariable analyses, independent predictors of mortality were age, damage score, and renal failure, and a trend was observed for BMI and smoking history. Common primary causes of death included cardiovascular diseases (CVDs) (29 patients, 35%), malignancies (22, 27%), and SLE (10, 12%). Infections were the immediate cause of death in 16 cases (20%). Conclusion Multidimensional factors are associated with increased long-term mortality in SLE, and independent predictors include age, damage score, and renal failure. To improve the outcome of SLE, our results emphasize active treatment of CVDs and their risk factors, major organ manifestations of the disease and infections, and targeted cancer screening.

Despite advancements in surgical techniques and perioperative care, postoperative bleeding and neurological complications remain significant concerns after bioprosthetic surgical aortic valve replacement (SAVR). The present study assessed the incidence of short-term and long-term major bleeding and strokes and their association with antithrombotic treatment after isolated bioprosthetic SAVR. The CAREAVR study included 721 patients who underwent isolated bioprosthetic SAVR at four Finnish university hospitals between 2002 and 2014. The day-to-day information on short-term antithrombotic treatment was available from a subgroup including 227 patients. The median follow-up time was 4.9 (interquartile range 3.0-7.0) years. During the 30-day postoperative period, in the subgroup of 227 patients, 31 (13.7%) patients experienced a major bleeding event, and 13 (5.7%) patients a major stroke. A vast majority of the bleedings (80.6%) occurred within two days after the surgery, and the tail effect of preoperative aspirin was present in 54.8% of episodes, indicating unintentional antithrombotic effect. During the long-term follow-up (>30days after the index surgery), major bleeding episodes occurred in 40 (5.5%) patients, and 47 (6.5%) patients experienced a major stroke. Overall, 23 (57.5%) of the patients with major bleeding and 13 (27.7%) of the patients experiencing major stroke were on OAC during the event. The incidence of perioperative major bleeding was over two-fold compared to major stroke, the majority occurring during the tail effect of preoperatively used aspirin. During the long-term follow-up, the rates of stroke and major bleeds were similar, and most bleeding episodes occurred while on OAC.

Non-communicable diseases are the leading causes of premature mortality worldwide. Both genetic predispositions and environmental exposures affect disease risk. While biobanks have increased understanding of genetic predictors of these diseases, environmental influences are expected to have a greater impact on disease development. Individuals also create their own environments and lifestyles based on genetically regulated preferences, leading to gene-environment interactions that require large datasets to study. Finnish biobanks typically lack sufficient lifestyle and environmental data, which limits their use. We present a protocol for a biobank-recall study (BioRecall) to collect data on lifestyle and environmental exposures and combine these findings with genotypes, biological samples and clinical outcomes. All previously genotyped donors from the Central Finland Biobank who have been diagnosed with type 2 diabetes and have consented to recall will be invited to participate in the pilot study. The preliminary feasibility assessment reveals that there are 1580 suitable candidates. Participants will complete an electronic questionnaire on a secure online platform. The questionnaire includes validated questions on lifestyles, anthropometrics, weight loss history, health, symptoms, work characteristics, emotional states and residential environments. Postcode information will facilitate the addition of spatial environmental data. Genotype and related clinical data will be provided in the study in accordance with the Finnish Biobank Act and combined with questionnaire data. The Human Sciences Ethics Committee of the University of Jyväskylä delivered a favourable statement regarding the study protocol (1671/13.00.04.00/2023). Central Finland Biobank approved the research plan (no: BB24-0333-A01). The data collected will be returned to the Central Finland Biobank for research purposes with the participants' consent. Permission for data usage can then be applied through standard protocols of the Fingenious service (https://site.fingenious.fi/en/). If successful, the study will be expanded to other donors and Finnish biobanks.

The impact of vitamin D on fall incidence remains controversial. We studied the effect of 5 years of vitamin D3 supplementation on the risk of falls in a double-blind, placebo-controlled randomized trial with generally healthy, community-dwelling men and women in Finland. The study included 2495 participants, men aged ≥ 60 and women aged ≥ 65, who were randomized into three arms: 1600 IU/day or 3200 IU/day of vitamin D3 or placebo. A random subgroup of 551 participants underwent more detailed examinations. Falls and fall-related injuries were collected with questionnaires at months 0, 12, 24, 36, and 60. General linear mixed models and generalized linear models were used for analyses. Over the 5-year follow-up, a similar fall risk of 55% and fall-injury risk of 11% were observed in the placebo, 1600 IU/day, and 3200 IU/day arms, with the mean number of falls and fall-injuries per person-year of 1.26 (95% CI 1.14-1.38) and 0.07 (95% CI 0.06-0.08), respectively. Age, sex, or BMI did not modify the results. In the random subgroup, the mean baseline serum 25(OH)D concentration was 75 nmol/L (SD 18). After 12 months, the concentrations were 73, 100, and 120 nmol/L in the placebo, 1600 IU/day, and 3200 IU/day arms, respectively. Five-year vitamin D3 supplementation of 1600 IU/day or 3200 IU/day did not affect the overall risk of falls or fall injuries among generally healthy, largely vitamin D sufficient men and women. The findings do not support the use of high vitamin D doses for fall prevention in such populations. ClinicalTrials.gov: NCT01463813, https://clinicaltrials.gov/ct2/show/NCT01463813.

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. The initial injury initiates a cascade of secondary injury mechanisms, including neuroinflammation and disruption of brain connectivity. In this study, we used the lateral fluid percussion injury model of TBI to investigate the relationship between secondary thalamic inflammation and corticothalamic connectivity disruptions. For this, we followed rats for six months post-injury, during which functional magnetic resonance imaging (fMRI) was conducted under light sedation, as well as diffusion tensor imaging (DTI) and positron emission tomography (PET). PET imaging with [18F]-FEPPA revealed neuroinflammation in the subacute stage in several ipsilateral thalamic nuclei, including the ventral posterior nucleus and lateral nucleus. In the fMRI analysis, we observed initial corticothalamic hypoconnectivity, which partially resolved by six months post-injury. DTI showed persistent increased mean, axial, and radial diffusivity in the ipsilateral thalamic nuclei from two months post-injury. Histological examination confirmed chronic thalamic neuroinflammation and neuronal loss eight months post-TBI. Correlation analyses showed that subacute thalamic neuroinflammation was associated with long-term structural and functional changes. These findings suggest that secondary thalamic inflammation contributes to enduring corticothalamic connectivity disruptions, which may underlie cognitive and sensorimotor deficits observed after TBI.

Healthcare decision-making (DM) has shifted from a paternalistic model to shared DM, where professionals contribute with clinical expertise and patients share their values and preferences. Simultaneously, access to online health information influences how patients engage in decisions concerning care. This study examined perceived DM experiences during doctor's appointments and online health information-seeking among older adults and individuals with long-term conditions. A total of 736 Finnish respondents (mean age 68 years) completed an online survey. The Shared Decision-Making Questionnaire (SDM-Q-9-FIN) assessed involvement in clinical decisions. Most participants reported feeling involved, with a mean SDM-Q-9 score of 25.96/36. Longer appointment duration (β = .50, P < .001), higher education attainment, and better health status were positively associated with perceived involvement. Adherence to treatment also enhanced DM experiences. Nearly half (48.6%) did not seek online health information before appointments. Respondents from patient associations reported more frequent information-seeking. The findings suggest that adequate consultation time and tailored communication can enhance DM. Support should be prioritized for patients with lower health status or limited health literacy.

The aim was to evaluate the toxicities and survival of patients with inoperable vulvar cancer treated using brachytherapy (BT). Patients treated at Kuopio University Hospital, Finland, during years 2007-2022 were retrospectively analyzed. Twenty-seven patients with vulvar cancer received high-dose-rate (HDR) interstitial brachytherapy (BT), most of them after external beam radiotherapy (EBRT). Nineteen had primary locally advanced vulvar cancer, and 8 had recurrent cancer. The mean EBRT prescription dose was 48.5 Gy (39-60 Gy) in 13-33 fractions. Eighteen patients (67%) had cisplatin as a radiosensitizer. EBRT was followed by BT (16-36 Gy in 3-8 fractions). The mean HR-CTV (high-risk clinical target volume) D90 EBRT + BT dose was 71.2 Gy (EQD₂). The mean follow-up time was 30 months. The 2-year progression-free survival (PFS) was 41% in the primary cancer group and 38% in the recurrence group. The 2-year overall survival (OS) was 56% and 63%, respectively. There were 12/19 (63%) recurrences in the primary cancer group. In the recurrent cancer group, 4 out of 8 (50%) patients had a subsequent recurrence. 7/27 (26%) patients suffered from grade 3-4 late toxicities. Before EBRT, the median size of the tumors was 3.8 cm. Patients with a tumor ≥ 3.8 cm had significantly worse OS than patients with tumors <3.8 cm, 45 months and 54 months, respectively (p = 0.022). The use of radiosensitizing chemotherapy also predicted better overall survival (p = 0.037). Definitive radiation therapy, including EBRT and BT, is a potential option in the management of inoperable vulvar cancer. To avoid toxicities, the proper radiation doses are to be found.