The association between inflammation, arterial stiffness, oxidized LDL and cardiovascular disease in Finnish men with metabolic syndrome - a 15-year follow-up study.

Background: All-cause mortality and cardiovascular disease are increased in subjects with metabolic syndrome (MetS). Risk scores are used to predict individual risk of heart disease. We performed a long-term follow-up study to investigate whether risk scores and cardiovascular risk factors such as arterial stiffness, high-sensitive C-reactive protein (hs-CRP) and oxidized LDL (OxLDL) can be used to predict cardiovascular events in Finnish men with MetS.

Single-cell functional genomics reveals determinants of sensitivity and resistance to natural killer cells in blood cancers.

Cancer cells can evade natural killer (NK) cell activity, thereby limiting anti-tumor immunity. To reveal genetic determinants of susceptibility to NK cell activity, we examined interacting NK cells and blood cancer cells using single-cell and genome-scale functional genomics screens. Interaction of NK and cancer cells induced distinct activation and type I interferon (IFN) states in both cell types depending on the cancer cell lineage and molecular phenotype, ranging from more sensitive myeloid to less sensitive B-lymphoid cancers.

Type 2 diabetes and cognitive performance in middle age: a cross-sectional study.

Introduction: Type 2 diabetes has been associated with cognitive decrements already in middle-age. However, the sample sizes of the studies have been small and the neuropsychological tests used have been heterogeneous. In addition, only a few studies have matched the groups in terms of age, education and gender.

Infrared Thermography Compared to Standard Care in the Prevention and Care of Diabetic Foot: A Cost Analysis Utilizing Real-World Data and an Expert Panel.

Aim: Infrared thermography (IRT) is a non-invasive technology for screening and early detection of diabetic foot. Real-world data and the Delphi technique were used to assess IRT's potential effect on typical care pathways of diabetic foot and their costs in the Finnish healthcare setting.

Methods: The most typical care pathways of diabetic foot were identified from national healthcare registers from 2011 to 2017.

Exploring Transcriptomic Landscapes in Red Blood Cells, in Their Extracellular Vesicles and on a Single-Cell Level.

Being enucleated, RBCs lack typical transcriptomes, but are known to contain small amounts of diverse long transcripts and microRNAs. However, the exact role and importance of these RNAs are lacking. Shedding of extracellular vesicles (EVs) from the plasma membrane constitutes an integral mechanism of RBC homeostasis, by which RBCs remove unnecessary cytoplasmic content and cell membrane.

Foot-related diabetes complications: care pathways, patient profiles and costs.

Background: Foot-related diabetes complications reduce individual well-being, increase mortality and results in increased healthcare costs. Despite their notable stress on health services, studies examining the foot complication care pathways, especially from the viewpoint of health services, are limited. We aimed to identify the most typical care pathways following an initial foot-related diabetes complication, to characterize the patients on each pathway and calculate the related healthcare costs.

Glucose management team significantly improves glycaemic care and commitment to in-hospital guidelines within arthroplastic patients.

Background: Perioperative dysglycaemias are a risk for harm but guidelines to improve glucose management are poorly adhered to.

Aim: To determine whether a specialized team and diabetes education improves the implementation of guidelines and glucose values.

Methods: We conducted a prospective study of 611 nonselected, consecutive patients attending for elective hip or knee arthroplasty.

Antidiabetic Drugs and Prostate Cancer Prognosis in a Finnish Population-Based Cohort.

Background: Hyperinsulemia and glycemic control may play a role as prostate cancer prognostic factors, whereas use of certain antidiabetic drugs, that is metformin, could improve the prognosis. We examined the link between antidiabetic medication use and prostate cancer survival taking into account simultaneous use of multiple drugs.

Methods: The study cohort composed of 6,537 men in The Finnish Randomized Study of Screening for Prostate Cancer with prostate cancer diagnosed 1996 to 2009.

Patient-tailored design for selective co-inhibition of leukemic cell subpopulations.

The extensive drug resistance requires rational approaches to design personalized combinatorial treatments that exploit patient-specific therapeutic vulnerabilities to selectively target disease-driving cell subpopulations. To solve the combinatorial explosion challenge, we implemented an effective machine learning approach that prioritizes patient-customized drug combinations with a desired synergy-efficacy-toxicity balance by combining single-cell RNA sequencing with ex vivo single-agent testing in scarce patient-derived primary cells. When applied to two diagnostic and two refractory acute myeloid leukemia (AML) patient cases, each with a different genetic background, we accurately predicted patient-specific combinations that not only resulted in synergistic cancer cell co-inhibition but also were capable of targeting specific AML cell subpopulations that emerge in differing stages of disease pathogenesis or treatment regimens.

Immunogenomic Landscape of Hematological Malignancies.

Understanding factors that shape the immune landscape across hematological malignancies is essential for immunotherapy development. We integrated over 8,000 transcriptomes and 2,000 samples with multilevel genomics of hematological cancers to investigate how immunological features are linked to cancer subtypes, genetic and epigenetic alterations, and patient survival, and validated key findings experimentally. Infiltration of cytotoxic lymphocytes was associated with TP53 and myelodysplasia-related changes in acute myeloid leukemia, and activated B cell-like phenotype and interferon-γ response in lymphoma.

Perioperative hyperglycaemia in elective arthroplasties. Should we do better?

Background: Perioperative dysglycaemia is associated with deleterious outcomes but guidelines to improve glucose management are poorly or inconsistently adhered to. We evaluated glucose management among diabetic and non-diabetic patients undergoing elective hip or knee arthroplasty.

Methods: Capillary plasma glucose (CPG) was measured prospectively four times daily of 209 patients undergoing elective hip or knee surgery.

Different patterns of second-line treatment in type 2 diabetes after metformin monotherapy in Denmark, Finland, Norway and Sweden (D360 Nordic): A multinational observational study.

Aims: The understanding of second-line use of glucose-lowering drugs (GLDs) in the general population with type 2 diabetes (T2D) treatment is important as recent results have shown cardiovascular benefits with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). Our aim was to describe second-line GLD treatment patterns in four Nordic countries.

Methods: All T2D patients treated with GLD between 2006 and 2015 were identified in prescribed drug registries in Denmark, Finland, Norway and Sweden, and linked with National Patient and Cause of Death Registries.

Absence of NEFL in patient-specific neurons in early-onset Charcot-Marie-Tooth neuropathy.

Objective: We used patient-specific neuronal cultures to characterize the molecular genetic mechanism of recessive nonsense mutations in neurofilament light () underlying early-onset Charcot-Marie-Tooth (CMT) disease.

Methods: Motor neurons were differentiated from induced pluripotent stem cells of a patient with early-onset CMT carrying a novel homozygous nonsense mutation in . Quantitative PCR, protein analytics, immunocytochemistry, electron microscopy, and single-cell transcriptomics were used to investigate patient and control neurons.

Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer.

Background: Diabetic men have lowered overall risk of prostate cancer (PCa), but the role of hyperglycaemia is unclear. In this cohort study, we estimated PCa risk among men with diabetic fasting blood glucose level.

Methods: Participants of the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) were linked to laboratory database for information on glucose measurements since 1978.

Spatial aspects of oncogenic signalling determine the response to combination therapy in slice explants from Kras-driven lung tumours.

A key question in precision medicine is how functional heterogeneity in solid tumours informs therapeutic sensitivity. We demonstrate that spatial characteristics of oncogenic signalling and therapy response can be modelled in precision-cut slices from Kras-driven non-small-cell lung cancer with varying histopathologies. Unexpectedly, profiling of in situ tumours demonstrated that signalling stratifies mostly according to histopathology, showing enhanced AKT and SRC activity in adenosquamous carcinoma, and mitogen-activated protein kinase (MAPK) activity in adenocarcinoma.

Re-organizing inpatient care saves legs in patients with diabetic foot infections.

Aims: In this study, we evaluated the effects of the re-organization of inpatient care for patients with a diabetic foot infection, and the implementation of a specialized multi-disciplinary wound department at an academic tertiary hospital.

Methods: This was a retrospective cohort study, comprising 272 patients treated for diabetic foot infections in 2006-2007 (Group 1, n=124) and 2013-2014 (Group 2, n=148). In 2012, inpatient care of all chronic wounds was centralized at a single wound department with a multi-disciplinary team.

Cell of Origin Links Histotype Spectrum to Immune Microenvironment Diversity in Non-small-Cell Lung Cancer Driven by Mutant Kras and Loss of Lkb1.

Lung cancers exhibit pronounced functional heterogeneity, confounding precision medicine. We studied how the cell of origin contributes to phenotypic heterogeneity following conditional expression of Kras and loss of Lkb1 (Kras;Lkb1). Using progenitor cell-type-restricted adenoviral Cre to target cells expressing surfactant protein C (SPC) or club cell antigen 10 (CC10), we show that Ad5-CC10-Cre-infected mice exhibit a shorter latency compared with Ad5-SPC-Cre cohorts.

The Long-term Prospective Follow-up of Pancreatic Function After the First Episode of Acute Alcoholic Pancreatitis: Recurrence Predisposes One to Pancreatic Dysfunction and Pancreatogenic Diabetes.

Background: Data on the prevalence of pancreatic dysfunction after an episode of acute pancreatitis are conflicting. Our aim was to evaluate the natural course of endocrine and exocrine pancreatic function in the long-term follow-up after the first episode of acute alcoholic pancreatitis (AAP).

Methods: A total of 77 patients who survived their first episode of AAP between January 2001 and February 2005 were prospectively followed up for a maximum of 13 years.

Estimating bias in causes of death ascertainment in the Finnish Randomized Study of Screening for Prostate Cancer.

Background: Precise cause of death (CoD) ascertainment is crucial in any cancer screening trial to avoid bias from misclassification due to excessive recording of diagnosed cancer as a CoD in death certificates instead of non-cancer disease that actually caused death. We estimated whether there was bias in CoD determination between screening (SA) and control arms (CA) in a population-based prostate cancer (PCa) screening trial.

Methods: Our trial is the largest component of the European Randomized Study of Screening for Prostate Cancer with more than 80,000 men.

Obesity paradox disappears in coronary artery bypass graft patients during 20-year follow-up.

Aims: Although obesity is a risk factor for coronary heart disease (CHD), it might be associated with a favourable prognosis in patients with CHD. The aim of the study was to evaluate this so called 'obesity paradox' during a follow-up period of 20 years in patients who had undergone coronary artery bypass grafting (CABG).

Methods And Results: The study population consisted of 922 CHD patients who had undergone CABG between 1993 and 1994.

Efficacy and safety of liraglutide versus placebo added to basal insulin analogues (with or without metformin) in patients with type 2 diabetes: a randomized, placebo-controlled trial.

Aim: To confirm the superiority, compared with placebo, of adding liraglutide to pre-existing basal insulin analogue ± metformin in adults with inadequately controlled type 2 diabetes [glycated haemoglobin (HbA1c) 7.0-10.0% (53-86 mmol/mol)].

The putative tumor suppressor gene EphA3 fails to demonstrate a crucial role in murine lung tumorigenesis or morphogenesis.

Treatment of non-small cell lung cancer (NSCLC) is based on histological analysis and molecular profiling of targetable driver oncogenes. Therapeutic responses are further defined by the landscape of passenger mutations, or loss of tumor suppressor genes. We report here a thorough study to address the physiological role of the putative lung cancer tumor suppressor EPH receptor A3 (EPHA3), a gene that is frequently mutated in human lung adenocarcinomas.