Muodonmuutoksia ilman kotilokehtoa

Karin FilanderKehittämistyö murroksessa : sitoutuminen, sopeutuminen, ja vastarinta julkisella sektorilla 1990-luvulla. (Acta Universitatis Tamperensis 777) Väitöskirja. Tampereen yliopisto, 2000. ISBN 951-44-4946-

Pathogenic Variant Spectrum in Breast Cancer Risk Genes in Finnish Patients

Recurrent pathogenic variants have been detected in several breast and ovarian cancer (BC/OC) risk genes in the Finnish population. We conducted a gene-panel sequencing and copy number variant (CNV) analysis to define a more comprehensive spectrum of pathogenic variants in BRCA1, BRCA2, PALB2, CHEK2, ATM, BARD1, RAD51C, RAD51D, BRIP1, and FANCM genes in Finnish BC patients. The combined frequency of pathogenic variants in the BRCA1/2 genes was 1.8% in 1356 unselected patients, whereas variants in the other genes were detected altogether in 8.3% of 1356 unselected patients and in 12.9% of 699 familial patients. CNVs were detected in 0.3% of both 1137 unselected and 612 familial patients. A few variants covered most of the pathogenic burden in the studied genes. Of the BRCA1/2 carriers, 70.8% had 1 of 10 recurrent variants. In the other genes combined, 92.1% of the carrier patients had at least 1 of 11 recurrent variants. In particular, PALB2 c.1592delT and CHEK2 c.1100delC accounted for 88.9% and 82.9%, respectively, of the pathogenic variation in each gene. Our results highlight the importance of founder variants in the BC risk genes in the Finnish population and could be used in the designing of population screening for the risk variants

Real-World Clinical Outcomes in Biological Subgroups of Breast Cancer in the Hospital District of Southwest Finland

Background.Comparing breast cancer survival trends globally, Finland is among the top three countries in Europe. However, outcome data on breast cancer subgroups in the Finnish population are limited. This retrospective, registry-based study aimed to assess patient characteristics and clinical outcomes of different breast cancer subgroups in early (EBC) and metastatic breast cancer (MBC) in a real-life clinical setting.Materials and Methods.The study consisted of 6,977 adult, female patients with breast cancer diagnosed in Southwest Finland during 2005-2018. Patients were divided into four mutually exclusive groups: human epidermal growth factor receptor 2 positive (HER2+), triple negative, HER2-/hormone receptor positive (HR+), and HER2 and/or HR status unknown, and further into patients with EBC and MBC. Overall survival (OS) was assessed as a clinical outcome, as well as the following real-world (rw) clinical outcomes: disease-free survival (rwDFS), progression-free survival (rwPFS), and distant recurrence-free interval (rwDRFI).Results.Within EBC, 5-year survival was the highest (88%) in HER2-/HR+, followed by 85% in HER2+, and 75% in triple negative. The rwDFS varied significantly in EBC (5-year rwDFS HER2 -/HR+, HER2+, triple negative: 87%, 80%, 71% respectively). In MBC, median survival was 2 years for both HER2-/HR+ and HER2+ and markedly shorter for triple negative (0.8 years). Independent predictors of mortality were age (hazard ratio [HR], 1.1), other subgroups than HER2-/HR+ (HR, 1.2-1.9), metastatic disease (HR, 9.8), and other malignancies (HR, 2.7).Conclusion.This registry-based study demonstrates significant differences in breast cancer outcomes on the subgroup level, as well as poorer outcomes compared with clinical trials, giving complementary insight on clinical characteristics in an unselected patient population.Implications for Practice:This retrospective, registry-based study assessed the clinical outcomes of different breast cancer subgroups in 6,977 adult, female patients with breast cancer diagnosed in Southwest Finland during 2005-2018. Results demonstrated significant variation in the survival between subgroups in both early breast cancer and metastatic breast cancer, as well as differences between unselected patients representing the standard of care and randomized clinical trials. Although, according to the global comparison of survival trends, the net survival of patients with breast cancer in Finland is generally high, there is great variation between subgroups. These real-life breast cancer data provide tools to further evaluate medical need in different breast cancer subgroups.</div

Blood donation screening for hepatitis B virus core antibodies: The importance of confirmatory testing and initial implication for rare blood donor groups

Background and Objectives: Exclusion of blood donors with hepatitis B virus (HBV) core antibodies (anti‐HBc) prevents transfusion‐transmitted HBV infection but can lead to significant donor loss. As isolated anti‐HBc positivity does not always indicate true past HBV infection, we have investigated the effectiveness of confirmatory anti‐HBc testing and the representation of rare blood groups in anti‐HBc‐positive donors. Materials and Methods: Three hundred ninety‐seven HBV surface antigen‐negative and anti‐HBc initially reactive blood donor samples were tested by five different anti‐HBc assays. Results: Eighty percentage of samples reactive in Architect anti‐HBc assay were positive by the Murex assay and anti‐HBc neutralization. Eleven out of 397 samples showed discordant results in supplementary testing from the Murex confirmatory test result, and five remained undetermined following extensive serological testing. Thirty‐eight percentage of anti‐HBc‐positive donors identified as minority ethnic groups compared with 11% representation in anti‐HBc‐negative donors (p < 0.0001); the frequency of the Ro blood group in anti‐HBc‐positive donors was 18 times higher in non‐white ethnic groups. Conclusion: Using two anti‐HBc assays effectively enabled the identification of HBV‐exposed and potentially infectious donors, their deferral and potential clinical follow‐up. However, the exclusion of confirmed anti‐HBc‐positive donors will still impact the supply of rare blood such as Ro

Opas kaivannaisjätteiden hallinnan MWEI BREF -vertailuasiakirjan parhaita käyttökelpoisia tekniikoita koskevien päätelmien soveltamiseen

Tässä oppaassa kuvataan kaivannaisjätteiden hallinnan sekä kaivannaisjätteistä aiheutuvien haitallisten vaikutusten ehkäisyn ja vähentämisen parhaat käyttökelpoiset tekniikat (BAT). Opas perustuu kaivannaisjätteiden hallinnan parhaita käyttökelpoisia tekniikoita koskevaan vertailuasiakirjaan "Best Available Techniques Reference Document for the Management of Waste from Extractive Industries” ja Suomen kansallisiin ohjeistuksiin, oppaisiin sekä lainsäädäntöön. Oppaassa käsitellään kaivannaisjätealueisiin liittyviä parhaita käyttökelpoisia tekniikoita läpi kaivannaisjätealueen elinkaaren. Oppaan yleiset BAT-päätelmät käsittelevät johtamista, tiedon keruuta ja hallintaa sekä kaivannaistoiminnan jätehierarkiaa. Riskiperusteiset BAT-päätelmät puolestaan kuvaavat tekniikoita, joilla ehkäistään ja vähennetään ympäristöön ja ihmisten terveyteen kohdistuvia vaikutuksia sekä tekniikoita, joilla varmistetaan kaivannaisjätteen sijoitusalueiden rakenteellinen vakavuus sekä kaivannaisjätteen fysikaalinen ja kemiallinen pysyvyys. Opas tukee vertailuasiakirjassa esitettyjen BAT-päätelmien soveltamista kaivannaisjätteiden hallinnassa ja sitä voidaan hyödyntää kaivannaisteollisuuden toiminnan suunnittelussa, toteuttamisessa sekä kehittämisessä

Hydroxychloroquine reduces interleukin-6 levels after myocardial infarction : The randomized, double-blind, placebo-controlled OXI pilot trial

Objectives: To determine the anti-inflammatory effect and safety of hydroxychloroquine after acute myocardial infarction. Method: In this multicenter, double-blind, placebo-controlled OXI trial, 125 myocardial infarction patients were randomized at a median of 43 h after hospitalization to receive hydroxychloroquine 300 mg (n = 64) or placebo (n = 61) once daily for 6 months and, followed for an average of 32 months. Laboratory values were measured at baseline, 1, 6, and 12 months. Results: The levels of interleukin-6 (IL-6) were comparable at baseline between study groups (p = 0.18). At six months, the IL-6 levels were lower in the hydroxychloroquine group (p = 0.042, between groups), and in the on-treatment analysis, the difference at this time point was even more pronounced (p = 0.019, respectively). The high-sensitivity C-reactive protein levels did not differ significantly between study groups at any time points. Eleven patients in the hydroxychloroquine group and four in the placebo group had adverse events leading to in-terruption or withdrawal of study medication, none of which was serious (p = 0.10, between groups). Conclusions: In patients with myocardial infarction, hydroxychloroquine reduced IL-6 levels significantly more than did placebo without causing any clinically significant adverse events. A larger randomized clinical trial is warranted to prove the potential ability of hydroxychloroquine to reduce cardiovascular endpoints after myocar-dial infarction. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).Peer reviewe

Recurrent moderate-risk mutations in Finnish breast and ovarian cancer patients

Mutations in BRCA1 and BRCA2 genes predispose to breast and ovarian cancer (BC/OC) with a high lifetime risk, whereas mutations in PALB2, CHEK2, ATM, FANCM, RAD51C and RAD51D genes cause a moderately elevated risk. In the Finnish population, recurrent mutations have been identified in all of these genes, the latest being CHEK2 c.319+2T>A and c.444+1G>A. By genotyping 3,156 cases and 2,089 controls, we estimated the frequencies of CHEK2 c.319+2T>A and c.444+1G>A in Finnish BC patients. CHEK2 c.319+2T>A was detected in 0.7% of the patients, and it was associated with a high risk of BC in the unselected patient group (OR = 5.40 [95% CI 1.58–18.45], p = 0.007) and similarly in the familial patient group. CHEK2 c.444+1G>A was identified in 0.1% of all patients. Additionally, we evaluated the combined prevalence of recurrent moderate‐risk gene mutations in 2,487 BC patients, 556 OC patients and 261 BRCA1/2 carriers from 109 families. The overall frequency of the mutations was 13.3% in 1,141 BRCA1/2‐negative familial BC patients, 7.5% in 1,727 unselected BC patients and 7.2% in 556 unselected OC patients. At least one moderate‐risk gene mutation was found in 12.5% of BRCA1 families and 7.1% of BRCA1 index patients, as well as in 17.0% of BRCA2 families and 11.3% of BRCA2 index patients, and the mutations were associated with an additional risk in the BRCA1/2 index patients (OR = 2.63 [1.15–5.48], p = 0.011). These results support gene panel testing of even multiple members of BC families where several mutations may segregate in different individuals.</p

Recurrent moderate-risk mutations in Finnish breast and ovarian cancer patients

Mutations in BRCA1 and BRCA2 genes predispose to breast and ovarian cancer (BC/OC) with a high lifetime risk, whereas mutations in PALB2, CHEK2, ATM, FANCM, RAD51C and RAD51D genes cause a moderately elevated risk. In the Finnish population, recurrent mutations have been identified in all of these genes, the latest being CHEK2 c.319+2T>A and c.444+1G>A. By genotyping 3,156 cases and 2,089 controls, we estimated the frequencies of CHEK2 c.319+2T>A and c.444+1G>A in Finnish BC patients. CHEK2 c.319+2T>A was detected in 0.7% of the patients, and it was associated with a high risk of BC in the unselected patient group (OR = 5.40 [95% CI 1.58-18.45], p = 0.007) and similarly in the familial patient group. CHEK2 c.444+1G>A was identified in 0.1% of all patients. Additionally, we evaluated the combined prevalence of recurrent moderate-risk gene mutations in 2,487 BC patients, 556 OC patients and 261 BRCA1/2 carriers from 109 families. The overall frequency of the mutations was 13.3% in 1,141 BRCA1/2-negative familial BC patients, 7.5% in 1,727 unselected BC patients and 7.2% in 556 unselected OC patients. At least one moderate-risk gene mutation was found in 12.5% of BRCA1 families and 7.1% of BRCA1 index patients, as well as in 17.0% of BRCA2 families and 11.3% of BRCA2 index patients, and the mutations were associated with an additional risk in the BRCA1/2 index patients (OR = 2.63 [1.15-5.48], p = 0.011). These results support gene panel testing of even multiple members of BC families where several mutations may segregate in different individuals.Peer reviewe

Blood donation screening for hepatitis B virus core antibodies: The importance of confirmatory testing and initial implication for rare blood donor groups

Background and ObjectivesExclusion of blood donors with hepatitis B virus (HBV) core antibodies (anti-HBc) prevents transfusion-transmitted HBV infection but can lead to significant donor loss. As isolated anti-HBc positivity does not always indicate true past HBV infection, we have investigated the effectiveness of confirmatory anti-HBc testing and the representation of rare blood groups in anti-HBc-positive donors.Materials and MethodsThree hundred ninety-seven HBV surface antigen-negative and anti-HBc initially reactive blood donor samples were tested by five different anti-HBc assays.ResultsEighty percentage of samples reactive in Architect anti-HBc assay were positive by the Murex assay and anti-HBc neutralization. Eleven out of 397 samples showed discordant results in supplementary testing from the Murex confirmatory test result, and five remained undetermined following extensive serological testing. Thirty-eight percentage of anti-HBc-positive donors identified as minority ethnic groups compared with 11% representation in anti-HBc-negative donors (p < 0.0001); the frequency of the Ro blood group in anti-HBc-positive donors was 18 times higher in non-white ethnic groups.ConclusionUsing two anti-HBc assays effectively enabled the identification of HBV-exposed and potentially infectious donors, their deferral and potential clinical follow-up. However, the exclusion of confirmed anti-HBc-positive donors will still impact the supply of rare blood such as Ro

Case-control analysis of truncating mutations in DNA damage response genes connects TEX15 and FANCD2 with hereditary breast cancer susceptibility

Several known breast cancer susceptibility genes encode proteins involved in DNA damage response (DDR) and are characterized by rare loss-of-function mutations. However, these explain less than half of the familial cases. To identify novel susceptibility factors, 39 rare truncating mutations, identified in 189 Northern Finnish hereditary breast cancer patients in parallel sequencing of 796 DDR genes, were studied for disease association. Mutation screening was performed for Northern Finnish breast cancer cases (n = 578-1565) and controls (n = 337-1228). Mutations showing potential cancer association were analyzed in additional Finnish cohorts.c.7253dupT in TEX15, encoding a DDR factor important in meiosis, associated with hereditary breast cancer (p = 0.018) and likely represents a Northern Finnish founder mutation. A deleterious c.2715 + 1G > A mutation in the Fanconi anemia gene, FANCD2, was over two times more common in the combined Finnish hereditary cohort compared to controls. A deletion (c.640_644del5) in RNF168, causative for recessive RIDDLE syndrome, had high prevalence in majority of the analyzed cohorts, but did not associate with breast cancer. In conclusion, truncating variants in TEX15 and FANCD2 are potential breast cancer risk factors, warranting further investigations in other populations. Furthermore, high frequency of RNF168 c.640_644del5 indicates the need for its testing in Finnish patients with RIDDLE syndrome symptoms.Peer reviewe