Publications by authors named "Antti Karlsson"

9 Publications

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Are Breast Cancer Nomograms Still Valid to Predict the Need for Axillary Dissection?

Oncology 2021 10;99(6):397-401. Epub 2021 Mar 10.

Department of Oncology, University of Turku and Turku University Hospital, Turku, Finland.

Background: Nomograms can help in estimating the nodal status among clinically node-negative patients. Yet their validity in external cohorts over time is unknown. If the nodal stage can be estimated preoperatively, the need for axillary dissection can be decided.

Objectives: The aim of this study was to validate three existing nomograms predicting 4 or more axillary lymph node metastases.

Method: The risk for ≥4 lymph node metastases was calculated for n = 529 eligible breast cancer patients using the nomograms of Chagpar et al. [Ann Surg Oncol. 2007;14:670-7], Katz et al. [J Clin Oncol. 2008;26(13):2093-8], and Meretoja et al. [Breast Cancer Res Treat. 2013;138(3):817-27]. Discrimination and calibration were calculated for each nomogram to determine their validity.

Results: In this cohort, the AUC values for the Chagpar, Katz, and Meretoja models were 0.79 (95% CI 0.74-0.83), 0.87 (95% CI 0.83-0.91), and 0.82 (95% CI 0.76-0.86), respectively, showing good discrimination between patients with and without high nodal burdens.

Conclusion: This study presents support for the use of older breast cancer nomograms and confirms their current validity in an external population.
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http://dx.doi.org/10.1159/000514616DOI Listing
June 2021

The Gaucher earlier diagnosis consensus point-scoring system (GED-C PSS): Evaluation of a prototype in Finnish Gaucher disease patients and feasibility of screening retrospective electronic health record data for the recognition of potential undiagnosed patients in Finland.

Mol Genet Metab Rep 2021 Jun 9;27:100725. Epub 2021 Feb 9.

Takeda Oy, Ilmalantori 1, 00101 Helsinki, Finland.

Background: Gaucher disease (GD) is a rare inherited multiorgan disorder, yet a diagnosis can be significantly delayed due to a broad spectrum of symptoms and lack of disease awareness. Recently, the prototype of a GD point-scoring system (PSS) was established by the Gaucher Earlier Diagnosis Consensus (GED-C) initiative, and more recently, validated in Gaucher patients in UK. In our study, the original GED-C PSS was tested in Finnish GD patients. Furthermore, the feasibility of point scoring large electronic health record (EHR) data set by data mining to identify potential undiagnosed GD cases was evaluated.

Methods: This biobank study was conducted in collaboration with two Finnish biobanks. Five previously diagnosed Finnish GD patients and ~ 170,000 adult biobank subjects were included in the study. The original PSS was locally adjusted due to data availability issues and applied to the Finnish EHR data representing special health care recordings.

Results: All GD patients had high levels of the biomarker lyso-Gb1 and deleterious mutations. One patient was a compound heterozygote with a novel variant, potentially pathogenic mutation. Finnish EHR data allowed the retrospective assessment of 27-30 of the 32 original GED-C signs/co-variables. Total point scores of GD patients were high but variable, 6-18.5 points per patient (based on the available data on 28-29 signs/co-variables per patient). All GD patients had been recorded with anaemia while only three patients had a record of splenomegaly. 0.72% of biobank subjects were assigned at least 6 points but none of these potential "GD suspects" had a point score as high as 18.5. Splenomegaly had been recorded for 0.25% of biobank subjects and was associated with variable point score distribution and co-occurring ICD-10 diagnoses.

Discussion: This study provides an indicative GED-C PSS score range for confirmed GD patients, also representing potential mild cases, and demonstrates the feasibility of scoring Finnish EHR data by data mining in order to screen for undiagnosed GD patients. Further prioritisation of the "GD suspects" with more developed algorithms and data-mining approaches is needed.

Funding: This study was funded by Shire (now part of Takeda).
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http://dx.doi.org/10.1016/j.ymgmr.2021.100725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875822PMC
June 2021

High tumor mutation burden predicts favorable outcome among patients with aggressive histological subtypes of lung adenocarcinoma: A population-based single-institution study.

Neoplasia 2020 09 22;22(9):333-342. Epub 2020 Jun 22.

Institute of Biomedicine, University of Turku and Department of Pathology, Turku University Hospital, Kiinamyllynkatu 10, 20520 Turku, Finland.

Objectives: Tumor mutation burden (TMB) is an emerging predictive cancer biomarker. Few studies have addressed the prognostic role of TMB in non-small cell lung carcinoma, with conflicting results. Moreover, the association of TMB with different histological subtypes of lung adenocarcinoma has hitherto not been systematically evaluated. Here we studied the prognostic value of TMB and its distribution in different histological subtypes of lung adenocarcinomas in a retrospective cohort using the most recent updated classification guidelines.

Materials And Methods: 176 surgically resected stage I-IV lung adenocarcinomas were histologically reclassified according to WHO 2015 guidelines. A modified classification subdividing the acinar subtype into classic acinar, complex glandular and cribriform subtypes was further applied and potentially prognostic histopathological characteristics such as tumor-infiltrating lymphocytes were evaluated. 148 patients with stage I-III tumors and complete follow-up data were included in the survival analyses. TMB was determined by a commercial next generation sequencing panel from 131 tumors, out of which 105 had survival data available.

Results: Predominant micropapillary, solid and complex glandular as well as nonpredominant cribriform histological subtypes were associated with significantly shorter survival. High TMB concentrated in micropapillary, solid and acinar predominant subtypes. Interestingly, TMB ≥ 14 mutations/MB conferred a stage- and histology-independent survival benefit compared to TMB < 14 in multivariable analysis for overall (HR 0.284, 95% CI 0.14-0.59, P=0.001) and disease-specific survival (HR 0.213, 95% CI 0.08-0.56, P=0.002).

Conclusion: TMB was an independent biomarker of favorable prognosis in our cohort of lung adenocarcinoma despite being associated with predominant histological subtypes considered aggressive.
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http://dx.doi.org/10.1016/j.neo.2020.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317687PMC
September 2020

Development of self-assessed work ability among middle-aged asthma patients-a 10 year follow-up study.

J Asthma 2020 May 13:1-9. Epub 2020 May 13.

Pulmonary Diseases and Clinical Allergology, Turku University Hospital, Turku, Finland.

The prevalence of asthma has been growing among working age people over the last decades. In this study, we examine the development of Work Ability Score (WAS) among middle-aged asthmatics in a longitudinal setting, in order to find risk factors for poor development. We followed the development of WAS trends during 10 years in a cohort of 529 middle-aged asthmatics, who were active in working life. Follow-up questionnaires were mailed in years 1, 2, 4, 6, 8, and 10. To study the development of WAS over time, we computed the discrete Frechet distance, which describes the similarity between the shapes of WAS curves. Sixty-eight percent of the patients' WAS remained good or excellent throughout the follow-up period, while 24% of the patients WAS trend remained moderate. However, in 8%, the WAS was poor already in baseline and decreased further throughout the study. Using logistic regression, the moderate/poor development was associated significantly with high body mass index (BMI), pack years, adult onset asthma, physically strenuous work, number of co-morbidities, especially in psychiatric conditions, hypertension, and gastroesophageal reflux disease(GERD). When the model was adjusted for age and gender, adulthood onset of asthma and pack years lost their significance. Based on medication (high dose of inhaled corticosteroids (ICS) and second controller in use), 8% of the patients had severe asthma. In the great majority of middle-aged asthma patients WAS remained stable throughout the follow-up period. However, 8% of the patients, who had more severe asthma and multiple co-morbidities, showed significantly poorer outcomes.
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http://dx.doi.org/10.1080/02770903.2020.1759089DOI Listing
May 2020

The Burden Of Chronic Obstructive Pulmonary Disease (COPD) In Finland: Impact Of Disease Severity And Eosinophil Count On Healthcare Resource Utilization.

Int J Chron Obstruct Pulmon Dis 2019 25;14:2409-2421. Epub 2019 Oct 25.

Division of Medicine, Department of Pulmonary Diseases, Turku University Hospital, Turku, Finland.

Purpose: The burden associated with chronic obstructive pulmonary disease (COPD) is substantial. The objectives of this study were to describe healthcare resource utilization (HCRU) and HCRU-associated costs in patients with COPD in Finland, according to disease severity and blood eosinophil count (BEC).

Patients And Methods: This non-interventional, retrospective registry study (GSK ID: HO-17-17558) utilized data from the specialist care hospital register. Data extraction was from first hospital visit with a COPD diagnosis (index date) from January 1, 2004 until December 31, 2015 or death. Patients (aged >18 years with ≥1 report of post-bronchodilation forced expiratory volume in 1 s (FEV)/forced vital capacity (FVC) ratio <0.7) were categorized as having non-severe or severe COPD (FEV >50% or ≤50% of reference, respectively). Patients who were initially non-severe but progressed to severe were classified as having progressing COPD. Patients without spirometry registry data were classified as having clinically verified COPD. Patients were grouped according to BEC (≥300 cells/μL, <300 cells/μL or BEC unknown). HCRU, estimated associated costs and mortality were evaluated according to COPD severity and BEC.

Results: There were 9042 patients with COPD; 340 non-severe, 326 progressing, 394 severe, and 7982 clinically verified. BEC was available for 31.8% of patients. The mean follow-up time was 3.7-6.5 years in the classified patient-groups. All-cause mortality was 46% during follow-up. Severe COPD was associated with more COPD-related HCRU and higher mortality than non-severe COPD. Patients with BEC ≥300 cells/μL had higher overall HCRU but improved survival compared with those with BEC <300 cells/μL. Overall direct costs were similar across COPD severity categories, 3300-3900€/patient-year, although COPD-related costs were higher in patients with severe versus non-severe COPD.

Conclusion: This study demonstrated a substantial burden associated with severe and/or eosinophilic COPD for patients in Finland.
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http://dx.doi.org/10.2147/COPD.S222581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818542PMC
April 2020

Health care resource utilization and characteristics of patients with eosinophilic asthma in secondary health care in Finland.

Eur Clin Respir J 2018 15;5(1):1458560. Epub 2018 Apr 15.

Medaffcon Oy, Espoo, Finland.

: Eosinophilic airway inflammation is common in asthma patients and appears to be associated with severe exacerbations and loss of asthma control. : To describe the resource utilization and clinical characteristics of patients with eosinophilic asthma. : Asthma patients ≥18 years with ≥1 blood eosinophil count in secondary care (South West Finland) during 2003‒2013 were included. Clinical characteristics (age, lung function, body mass index, and comorbidities) and asthma-related resource utilization (hospital admissions, outpatient visits, and emergency room [ER] visits) were retrieved. Resource utilization rates were compared for patients with blood eosinophil ≤ or >300 cells/μL, using adjusted negative binomial regression models. : Overall, 4,357 eligible patients were identified (mean age 60 years, females 68%), of which 1,927 (44%) had >300 eosinophil cells/μL blood. Patients with ≤300 and >300 eosinophil counts, exhibited similar clinical characteristics, including advanced age, poor lung function, and overweight. Comorbidities such as pneumonia, sinusitis, and nasal polyps, were more frequent among those with >300 eosinophil cells/μL blood compared with patients with lower counts. Eosinophil counts >300 cells/μL were associated with greater hospital admissions (rate ratio [RR] [95% confidence interval CI]: 1.13 [1.02;1.24]) and outpatient visits (RR [95% CI]: 1.11 [1.03;1.20]) compared with patients with lower eosinophil counts. Rates of ER visits were similar between the patient groups (RR [95% CI]: 0.99 [0.87;1.12]). : Hospital admissions and outpatient visits occurred more often for patients with eosinophil counts >300 cells/µL, than for patients with lower eosinophil counts. Routine blood eosinophil screening might be useful to identify patients with an eosinophilic phenotype eligible for more targeted treatments.
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http://dx.doi.org/10.1080/20018525.2018.1458560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5912706PMC
April 2018

Quantitative Evaluation of 2 Scatter-Correction Techniques for F-FDG Brain PET/MRI in Regard to MR-Based Attenuation Correction.

J Nucl Med 2017 10 23;58(10):1691-1698. Epub 2017 Mar 23.

Department of Medical Physics, Turku University Hospital, Turku, Finland.

In PET, corrections for photon scatter and attenuation are essential for visual and quantitative consistency. MR attenuation correction (MRAC) is generally conducted by image segmentation and assignment of discrete attenuation coefficients, which offer limited accuracy compared with CT attenuation correction. Potential inaccuracies in MRAC may affect scatter correction, because the attenuation image (μ-map) is used in single scatter simulation (SSS) to calculate the scatter estimate. We assessed the impact of MRAC to scatter correction using 2 scatter-correction techniques and 3 μ-maps for MRAC. The tail-fitted SSS (TF-SSS) and a Monte Carlo-based single scatter simulation (MC-SSS) algorithm implementations on the Philips Ingenuity TF PET/MR were used with 1 CT-based and 2 MR-based μ-maps. Data from 7 subjects were used in the clinical evaluation, and a phantom study using an anatomic brain phantom was conducted. Scatter-correction sinograms were evaluated for each scatter correction method and μ-map. Absolute image quantification was investigated with the phantom data. Quantitative assessment of PET images was performed by volume-of-interest and ratio image analysis. MRAC did not result in large differences in scatter algorithm performance, especially with TF-SSS. Scatter sinograms and scatter fractions did not reveal large differences regardless of the μ-map used. TF-SSS showed slightly higher absolute quantification. The differences in volume-of-interest analysis between TF-SSS and MC-SSS were 3% at maximum in the phantom and 4% in the patient study. Both algorithms showed excellent correlation with each other with no visual differences between PET images. MC-SSS showed a slight dependency on the μ-map used, with a difference of 2% on average and 4% at maximum when a μ-map without bone was used. The effect of different MR-based μ-maps on the performance of scatter correction was minimal in non-time-of-flight F-FDG PET/MR brain imaging. The SSS algorithm was not affected significantly by MRAC. The performance of the MC-SSS algorithm is comparable but not superior to TF-SSS, warranting further investigations of algorithm optimization and performance with different radiotracers and time-of-flight imaging.
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http://dx.doi.org/10.2967/jnumed.117.190231DOI Listing
October 2017

Quantum Zeno-type effect and non-Markovianity in a three-level system.

Sci Rep 2016 12 20;6:39061. Epub 2016 Dec 20.

Dip. Fisica, Universitá della Calabria, 87036 Arcavacata di Rende (CS) Italy.

We study the coexistence of the quantum Zeno-type effect and non-Markovianity for a system decaying in a structured bosonic environment and subject to a control field. The interaction with the environment induces decay from the excited to the ground level, which, in turn, is coherently coupled to another meta-stable state. The control of the strength of the coherent coupling between the stable levels allows the engineering of both the dissipation and of the memory effects, without modifying neither the system-reservoir interaction, nor environmental properties. We use this framework in two different parameter regimes corresponding to fast (bad cavity limit) and slow dissipation (good cavity limit) in the original and un-controlled qubit system. Our results show a non-monotonic behavior of memory effects when increasing the effectiveness of the Zeno-like freezing. Moreover, we identify a new source of memory effects which allows the persistence of non-Markovianity for long times while the excited state has already been depleted.
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http://dx.doi.org/10.1038/srep39061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5171700PMC
December 2016

Verifying the Quantumness of Bipartite Correlations.

Phys Rev Lett 2016 Jun 7;116(23):230403. Epub 2016 Jun 7.

Dipartimento di Matematica, Politecnico di Milano, Piazza Leonardo da Vinci 32, I-20133 Milano, Italy.

Entanglement is at the heart of most quantum information tasks, and therefore considerable effort has been made to find methods of deciding the entanglement content of a given bipartite quantum state. Here, we prove a fundamental limitation to deciding if an unknown state is entangled or not: we show that any quantum measurement which can answer this question for an arbitrary state necessarily gives enough information to identify the state completely. We also extend our treatment to other classes of correlated states by considering the problem of deciding if a state has negative partial transpose, is discordant, or is fully classically correlated. Remarkably, only the question related to quantum discord can be answered without resorting to full state tomography.
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http://dx.doi.org/10.1103/PhysRevLett.116.230403DOI Listing
June 2016