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1. Streptozocin/5-fluorouracil chemotherapy of pancreatic neuroendocrine tumours in the era of targeted therapy

Author: Dagmar Führer, Sarah Theurer, Harald Lahner, Nicole Unger, Kurt Werner Schmid, Jens M. Theysohn, Jan Rekowski, Annie Mathew, Karl-Heinz Jöckel, Ken Herrmann, and Anna Lisa Klocker
Subjects: medicine.medical_specialty, Survival, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Medizin, Gastroenterology, Streptozocin, Targeted therapy, Endocrinology, Pancreatic neuroendocrine tumor, Internal medicine, Objective response, medicine, Humans, 5-fluorouracil, Chemotherapy, Univariate analysis, Proportional hazards model, business.industry, medicine.disease, Pancreatic Neoplasms, Neuroendocrine Tumors, Treatment Outcome, Fluorouracil, Radionuclide therapy, Toxicity, Original Article, business, Progressive disease, medicine.drug
Abstract: Purpose The role of streptozocin-based chemotherapy (STZ CTx) in advanced, well-differentiated pancreatic neuroendocrine tumours (PanNET) and the best sequence of treatments in advanced PanNET are unclear. We examined the outcomes after STZ CTx in patients who had been selected according to the current therapeutic guidelines. Methods Data from 50 PanNET patients consecutively treated with STZ CTx between 2010 and 2018 were analysed. The endpoints of the study were the objective-response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results STZ CTx was the first-line treatment in 54% of patients. The PanNET grades were as follows: 6% G1, 88% G2, and 6% well-differentiated G3. The ORR was 38%. Stable disease was the best response in 38% of patients and 24% showed progressive disease. Treatment was discontinued because of toxicity in one patient. Median PFS and OS were 12 (95% confidence interval (CI), 8.5–15.5) and 38 months (95% CI, 20.4–55.6), respectively. In the Kaplan-Meier analysis, the median OS was 89 months (95% CI, 34.9–143.1) for STZ CTx as first-line therapy compared with 22 months (95% CI, 19.3–24.7; p = 0.001, log-rank test) for subsequent lines. Bone metastases negatively impacted survival (HR, 2.71, p = 0.009, univariate analysis, HR, 2.64, p = 0.015, multivariate analysis, and Cox regression). Conclusions In patients selected according to current guidelines, PFS, and OS after STZ CTx were lower than previously reported, whereas ORR was unchanged. First-line treatment was positively associated with OS and the presence of bone metastases was negatively associated with OS. Pre-treatment with targeted or peptide-receptor radionuclide therapy did not alter ORR, PFS, or OS.
Published: 2021

2. Monoclonal gammopathy of undetermined significance is associated with prostate cancer in a population-based cohort study

Author: Ulrich Dührsen, Andreas Stang, Börge Schmidt, Mirjam Frank, Jan Dürig, Susanne Moebus, Raimund Erbel, Karl-Heinz Jöckel, Nico Dragano, and Nicola Hornung
Subjects: Male, Oncology, medicine.medical_specialty, Epidemiology, Science, Population, Medizin, Monoclonal Gammopathy of Undetermined Significance, Risk Assessment, Article, Population based cohort, Prostate cancer, Risk Factors, immune system diseases, Internal medicine, hemic and lymphatic diseases, medicine, Humans, Prospective Studies, cardiovascular diseases, education, Cancer, Aged, Aged, 80 and over, education.field_of_study, Multidisciplinary, business.industry, Hazard ratio, Prostatic Neoplasms, Middle Aged, medicine.disease, Medicine, business, Haematological diseases, Monoclonal gammopathy of undetermined significance, Cohort study
Abstract: Register-based studies indicate a possible association of monoclonal gammopathy of undetermined significance (MGUS) and prostate cancer (PCa). Aim of the present study was to investigate the relationship between MGUS and PCa considering potentially shared risk factors. Data from the prospective population-based Heinz Nixdorf Recall cohort study of 2.385 men (age 45–85) were analyzed. MGUS was determined at three points in time; cases of cancer were assessed annually. Potentially shared risk factors were assessed at baseline. Hazard ratios (HR), adjusted for age and educational attainment, and corresponding 95%-confidence intervals (95%-CI) were calculated. 157 cases of MGUS and 143 incident cases of PCa were detected. Of 19 participants diagnosed with both, MGUS and incident PCa, only in one case MGUS did not clearly occur before PCa. MGUS was associated with PCa presenting a HR of 2.00 (95%-CI: 1.23–3.25). Stratified by isotype, IgM-MGUS showed the strongest association with PCa. There was no relevant change of the effect estimate when adjusting for potentially shared risk factors. We were able to give supporting evidence for an association between MGUS and PCa and pointed out its temporality. There was no indication that the observed association is due to shared risk factors. The present study indicated that different isotypes of MGUS differ in the strength of the effect on PCa-risk. Based on these findings, future studies investigating the pathophysiological background of the association will be needed.
Published: 2021

3. High Depressive Symptoms in Previously Undetected Diabetes – 10-Year Follow-Up Results of the Heinz Nixdorf Recall Study

Author: Susanne Moebus, Miriam Engel, Bernd Kowall, Silke Andrich, Charlotte Wittgens, Bernd Kulzer, Norbert Hermanns, Johannes Kruse, Andrea Icks, Andreas Stang, Burkhard Haastert, Christian Herder, Raimund Erbel, and Karl-Heinz Jöckel
Subjects: medicine.medical_specialty, Epidemiology, Population, Medizin, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, depressive symptoms, Diabetes mellitus, Internal medicine, medicine, Hyperinsulinemia, Clinical Epidemiology, Cumulative incidence, 030212 general & internal medicine, education, undetected diabetes, Stroke, Original Research, education.field_of_study, diabetes, business.industry, Odds ratio, medicine.disease, Confidence interval, prospective population-based cohort study, business, Cohort study
Abstract: Andrea Icks,1– 3 Charlotte Wittgens,1 Burkhard Haastert,2,4 Karl-Heinz Jöckel,5 Miriam Engel,5 Raimund Erbel,5 Silke Andrich,1,2 Johannes Kruse,6 Bernd Kulzer,7 Norbert Hermanns,7 Christian Herder,3,8,9 Susanne Moebus,5 Andreas Stang,5 Bernd Kowall5 1Institute for Health Services Research and Health Economics, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany; 2Institute for Health Services Research and Health Economics, Centre for Health and Society, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany; 3German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany; 4mediStatistica, Neuenrade, Germany; 5Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen, Germany; 6Institute for Psychosomatics and Psychotherapy, University Hospital Gießen, Gießen, Germany; 7Research Institute of the Diabetes Academy Mergentheim and Diabetes Centre Mergentheim, Bad Mergentheim, Germany; 8Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany; 9Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyCorrespondence: Andrea IcksInstitute for Health Services Research and Health Economics, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Auf’m Hennekamp 65, Düsseldorf, D-40225, GermanyTel +49 211 33 82 400Fax +49 211 33 82 677Email andrea.icks@uni-duesseldorf.deAim: To determine the 10-year cumulative incidence of high depressive symptoms in people with diagnosed and, in particular, previously undetected diabetes compared to those without diabetes in a population-based cohort study in Germany.Materials and Methods: We included 2813 participants (52.9% men, mean age (SD) 58.9 (7.7) years, 7.1% diagnosed diabetes, 5.6% previously undetected diabetes) from the Heinz Nixdorf Recall study. We calculated the odds ratios (OR) with 95% confidence intervals (CI) using multiple logistic regression analyses for diagnosed and undetected diabetes.Results: Cumulative 10-year incidences (95%-CI) of high depressive symptoms in participants with diagnosed diabetes, previously undetected diabetes, and without diabetes were 15.4% (10.7– 21.2), 10.1% (5.9– 15.9), and 12.4% (11.1– 13.8), respectively. Age-sex-adjusted ORs were 1.51 (1.01– 2.28) in participants with diagnosed diabetes compared to those without, 1.40 (0.92– 2.12) after adjustment for BMI, physical activity, education, and smoking, and 1.33 (0.87– 2.02) after further adjustment for stroke and myocardial infarction. ORs in participants with previously undetected diabetes were 0.96 (0.56– 1.65), 0.85 (0.49– 1.47), and 0.85 (0.49– 1.48), respectively, and lower in men than in women.Conclusion: As expected, we found an increased odds of developing high depressive symptoms in participants with diagnosed diabetes. However, the odds ratios decreased when we considered comorbidities and other covariates. Interestingly, in participants with previously undetected diabetes, the odds was not increased, even 10 years after detection of diabetes. These results support the hypothesis that high depressive symptoms develop due to diabetes-related burdens and comorbidities and not due to hyperglycemia or hyperinsulinemia.Keywords: diabetes, undetected diabetes, depressive symptoms, prospective population-based cohort study
Published: 2021

4. Cerebral cavernous malformations: Prevalence of cardiovascular comorbidities and allergic diseases compared to the normal population

Author: Ramazan Jabbarli, Karl-Heinz Jöckel, Ulrich Sure, Karsten H. Wrede, Bixia Chen, Philipp Dammann, Christoph Kleinschnitz, Michael Forsting, Börge Schmidt, Alejandro N Santos, Yuan Zhu, Dino Saban, Annika Herten, and Laurèl Rauschenbach
Subjects: Adult, Hemangioma, Cavernous, Central Nervous System, medicine.medical_specialty, Population, Medizin, Cohort Studies, Pathogenesis, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Epidemiology, Prevalence, medicine, Humans, 030212 general & internal medicine, education, education.field_of_study, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Odds ratio, Middle Aged, Cavernous malformations, medicine.disease, Magnetic Resonance Imaging, Cross-Sectional Studies, Neurology, Cohort, Female, Observational study, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Background To determine the prevalence of cardiovascular comorbidities and allergic diseases in patients with cavernous malformations of the central nervous system compared to the normal population. Methods Clinical and magnetic resonance imaging data of 1352 patients with cerebral cavernous malformations (CCM) from an observational, cross-sectional, single-institutional study were analyzed and compared to an age-and-gender stratified and matched sample from a population-based, epidemiological study assessing cardiovascular risk factors in the local normal population of the same area (RECALL study). Results Of 1352 patients, 810 (60%) were female. Mean age was 40.4 ± 16 years. 221 patients (16%) suffered from familial disease. Presence of cardiovascular risk factors and intake of certain drugs in the overall cohort was mostly equal to the normal population reference sample (n = 786). The prevalence of allergic diseases was found to be significantly higher in all CCM patients compared to the normal population (30% vs. 20%, odds ratio [OR] 1.35 [1.12-1.63]) and in sporadic CCM cases compared to the normal population and familial cases (32% vs. 20% (OR 1.46 [1.19-1.78], p = 0.0001) and 22% vs. 20%, respectively). Conclusions We present novel data on CCM using a large single-institution and population-based setup. The study elaborates disease characteristics of CCM patients in detail. For the first time, evidence for an unexplained high prevalence of allergic diseases in this patient population is described (differing between sporadic and familial cases), supporting the hypothesis that immune response is involved in the pathogenesis of CCM.
Published: 2021

5. Effects of Life Events and Social Isolation on Stroke and Coronary Heart Disease

Author: Karl W. Lauterbach, Janine Gronewold, Ela Emsal Duman, Miriam Engels, Martha Jokisch, Karl-Heinz Jöckel, Raimund Erbel, Dirk M. Hermann, Christoph Kleinschnitz, Sarah Van de Velde, and Thomas K.M. Cudjoe
Subjects: Gerontology, Distancing, Medizin, Vulnerability, Coronary Disease, Disease, Anxiety, Pandemic, Humans, Medicine, Social isolation, Stroke, Advanced and Specialized Nursing, Social stress, SARS-CoV-2, business.industry, COVID-19, medicine.disease, Coronary heart disease, Social Isolation, Communicable Disease Control, Human medicine, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: The current coronavirus disease 2019 (COVID-19) pandemic represents a severe, life-changing event for people across the world. Life changes may involve job loss, income reduction due to furlough, death of a beloved one, or social stress due to life habit changes. Many people suffer from social isolation due to lockdown or physical distancing, especially those living alone and without family. This article reviews the association of life events and social isolation with cardiovascular disease, assembling the current state of knowledge for stroke and coronary heart disease. Possible mechanisms underlying the links between life events, social isolation, and cardiovascular disease are outlined. Furthermore, groups with increased vulnerability for cardiovascular disease following life events and social isolation are identified, and clinical implications of results are presented.
Published: 2021

6. Genetic variations in G-protein signal pathways influence progression of coronary artery calcification: Results from the Heinz Nixdorf Recall study

Author: Jürgen Peters, Winfried Siffert, Raimund Erbel, Ulrich H. Frey, Nils Lehmann, Stefanie Klenke, and Karl-Heinz Jöckel
Subjects: 0301 basic medicine, medicine.medical_specialty, Medizin, Single-nucleotide polymorphism, Coronary Artery Disease, 030204 cardiovascular system & hematology, Polymorphism, Single Nucleotide, Article, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, GTP-Binding Proteins, Risk Factors, Internal medicine, Genetic variation, medicine, GNAS complex locus, Humans, cardiovascular diseases, Vascular Calcification, Coronary atherosclerosis, biology, business.industry, nutritional and metabolic diseases, Heritability, medicine.disease, 030104 developmental biology, Coronary artery calcification, Disease Progression, Cardiology, biology.protein, population characteristics, Cardiology and Cardiovascular Medicine, business, Signal Transduction, GNB3
Abstract: Background and aims Coronary artery calcification (CAC) is one of the most sensitive and specific markers of coronary atherosclerosis and believed to be heritable. We hypothesized that functionally relevant single-nucleotide polymorphisms (SNPs) in the G-protein signal pathway, which have been previously related to coronary artery disease, are associated with CAC progression. Methods 3108 participants from the Heinz Nixdorf Recall study with CAC measurements at both baseline (CACb) and 5-year follow-up (CAC5y) were included. We genotyped SNPs rs1042714 (ADRB2), rs6026584 and rs12481583 (GNAS), and rs5443 (GNB3) and defined a priori risk alleles derived from literature data. Regression analyses were applied to measures of 5-year CAC progression, unadjusted, adjusted for age, sex, and adjusted for age, sex, log(CACb+1) as well as for cardiovascular risk factors. Results The presence of one or more risk alleles was associated with a 26.9% (95% CI 5.5–52.4) increase in 5-year CAC progression (p = 0.011) and a 29.2% (95% CI 5.9–57.6) accelerated increase of CAC over the 5-year period compared to what was expected with respect to the baseline CAC percentile value (p = 0.012). Each of those risk alleles increased the 5-year CAC progression by 4.4% (95% CI 1.3–7.6, p = 0.006) and resulted in a 4.9% accelerated increase of CAC over the 5-year period (95% CI 1.6–8.4, p = 0.004). These unadjusted data did not change after adjustment. Conclusions Genetic variations in the G-protein signal pathway are associated with CAC progression in a cumulative fashion, indicating the importance of the pathway for genetic heritability in CAC progression and coronary artery disease.
Published: 2020

7. Associations between shift work and risk of colorectal cancer in two German cohort studies

Author: Lewin Eisele, Nico Dragano, Carsten Oliver Schmidt, Katharina Wichert, Henry Völzke, Andrea Keimer, Thomas Behrens, Andreas Stang, Wolfgang Hoffmann, Karl-Heinz Jöckel, Markus M. Lerch, Frederick Charles Roskoden, Sylvia Rabstein, Raimund Erbel, Marina Arendt, and Thomas Brüning
Subjects: Male, Physiology, Colorectal cancer, Medizin, 030209 endocrinology & metabolism, Cohort Studies, Shift work, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Risk Factors, Work Schedule Tolerance, Physiology (medical), Humans, Medicine, Poisson regression, Risk factor, Night work, business.industry, Shift Work Schedule, Cancer, medicine.disease, Circadian Rhythm, Study of Health in Pomerania, symbols, Colorectal Neoplasms, business, 030217 neurology & neurosurgery, Cohort study, Demography
Abstract: The association between shift work and the risk of colorectal cancer (CRC) is still unclear. Therefore, we studied the associations between exposure to shift or night work and incident CRC in two German population-based cohort studies, the Heinz Nixdorf Recall Study (HNR) and the Study of Health in Pomerania (SHIP). Including up to 6,903 participants, we analyzed the cohorts pooled and individually. We estimated incidence rate ratios (IRRs) with adjusted log-linear Poisson regression models with the natural logarithm of person-years as offset and performed subgroup analyses by sex and tumor localization in HNR. The pooled analysis revealed no increased risks for men working in night shifts (IRR: 1.03, 95% CI: 0.62; 1.71). In male HNR participants, we found an increased risk estimate for cancer of the distal colon in shift workers (IRR: 1.60, 95% CI: 0.53; 4.87) and in shift workers who did not perform night work (IRR: 3.93, 95% CI: 0.98; 15.70), but not in night workers. In SHIP, we observed elevated CRC risk estimates for rotating shift work including night work (IRR: 1.45, 95% CI: 0.72; 2.92) and for long-term exposure (IRR: 1.79, 95% CI: 0.81; 3.92) for men. In conclusion, night-shift work was not associated with CRC, although an increased risk was suggested for rotating shift work including nights in SHIP. The heterogeneity of shift-work jobs and schedules and associated lifestyle factors should be taken into account to disentangle a possible relationship between shift work and the risk for CRC in future investigations.
Published: 2020

8. Dynamic risk assessment based on positron emission tomography scanning in diffuse large B-cell lymphoma: Post-hoc analysis from the PETAL trial

Author: Ulrich Dührsen, Jan Rekowski, Andreas Hüttmann, Stefan P. Müller, Karl-Heinz Jöckel, Maher Hanoun, Christine Schmitz, Marcus Brinkmann, Ronald Boellaard, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, and CCA - Imaging and biomarkers
Subjects: Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Adolescent, Medizin, Standardized uptake value, Risk Assessment, Young Adult, 03 medical and health sciences, 0302 clinical medicine, International Prognostic Index, hemic and lymphatic diseases, Internal medicine, Post-hoc analysis, medicine, Humans, Positron emission, Aged, Retrospective Studies, Aged, 80 and over, medicine.diagnostic_test, business.industry, Proportional hazards model, Middle Aged, Prognosis, medicine.disease, Lymphoma, 030104 developmental biology, Positron emission tomography, Positron-Emission Tomography, 030220 oncology & carcinogenesis, Female, Lymphoma, Large B-Cell, Diffuse, business, Diffuse large B-cell lymphoma
Abstract: Background Valid prognostic tools are needed to guide risk-adjusted treatment approaches in patients with diffuse large B-cell lymphoma (DLBCL). Methods We assessed total metabolic tumor volume (TMTV) and standardized uptake value (SUV)-based interim positron emission tomography (iPET) response in 510 patients with DLBCL participating in the positron emission tomography-guided therapy of aggressive non-Hodgkin lymphomas (PETAL) trial (NCT00554164). TMTV was analyzed with a relative (SUV41max) and a fixed thresholding method (SUV4), and iPET was evaluated using the ΔSUVmax procedure. We determined associations between TMTV and international prognostic index (IPI) factors using Welch's t-test, investigated effects of TMTV, iPET response, and the IPI factors on time to progression (TTP), progression-free survival (PFS), and overall survival (OS) by Cox regression, and estimated the outcome using Kaplan–Meier curves. Findings TMTV was associated with all IPI factors except age. Irrespective of the thresholding method used, TMTV and iPET response were correlated with TTP, PFS, and OS, and remained the only independent outcome predictors in Cox regression analysis. By dichotomizing TMTV (cut-off: 328 cm³ by SUV41max) and iPET response (cut-off: 66% SUVmax reduction), we defined three groups at different risk of treatment failure (low [57.1% of patients]: low TMTV/good iPET response; intermediate [37.8%]: high TMTV/good iPET response or low TMTV/poor iPET response; and high [5.1%]: high TMTV/poor iPET response), with corresponding 2-year probabilities of 93.8% vs. 67.3% vs. 38.5% for TTP, 90.9% vs. 62.5% vs. 29.9% for PFS, and 95.5% vs. 77.4% vs. 37.1% for OS. Interpretation The PET-based risk model proposed may help identify patients who may benefit from treatment modifications or novel approaches.
Published: 2020

9. Trail Making Test Normative Data for the German Older Population

Author: Andreas Stang, Christian Weimar, Karl-Heinz Jöckel, Sarah Sanchez Hoffmann, Michael Specka, Bernd Kowall, Martha Jokisch, and Norbert Scherbaum
Subjects: 050103 clinical psychology, Trail Making Test, Population, Medizin, Neuropsychological Tests, 03 medical and health sciences, 0302 clinical medicine, Reference Values, medicine, Dementia, Humans, 0501 psychology and cognitive sciences, Cognitive Dysfunction, education, education.field_of_study, 05 social sciences, General Medicine, Center for Epidemiologic Studies Depression Scale, medicine.disease, Mental Status and Dementia Tests, Educational attainment, Psychiatry and Mental health, Clinical Psychology, Neuropsychology and Physiological Psychology, Categorization, Normative, Psychology, Neurocognitive, 030217 neurology & neurosurgery, Demography
Abstract: Objective We provide normative data for the Trail Making Test (TMT)-A and B and the derived scores B − A and B/A, for the German general population aged 57–84 years. Methods Data were derived from the third examination of the population-based Heinz Nixdorf Recall study. We excluded participants with a history of dementia or stroke, a depression score above cutoff (CES-D Center for Epidemiologic Studies Depression Scale score ≥ 18), or mild cognitive impairment according to a neurocognitive test battery. The normative sample (n = 2,182) was stratified by age, using the interval superposition approach, and by three levels of educational attainment (up to 10 years of schooling; >10 years of schooling; and university degree). Results We tabulated test performance scores at percentage rank thresholds 5, 10, 15, 20, 25, 50, 75, and 90. In multiple linear regression, TMT-A performance declined by 1 s each year of life, and TMT-B performance by 3 s; educational level had an impact of up to 30 s in TMT-B. TMT-B/A was only weakly associated with age and education. TMT-B and B − A correlated r = 0.96. Completion of the TMT-B within the time limit of 300 s was not achieved by 10.9% of participants >74 years, and especially by those >74 years who were on the lowest educational level (13.9%). Conclusions For TMT-A, TMT-B, and B − A, the narrow age categorization and distinction between three educational levels proved meaningful. The 300 s limit for the TMT-B impedes the identification of thresholds for very low performance in this age group and needs reconsideration.
Published: 2022

10. Perioperative course and quality of life in a prospective randomized multicenter phase III trial, comparing standard lobectomy versus anatomical segmentectomy in patients with non-small cell lung cancer up to 2 cm, stage IA (7th edition of TNM staging system)

Author: Walter Weder, Gunda Leschber, Thomas Krbek, Christian Kugler, Georgios Stamatis, Gerhard Weinreich, M.R. Müller, Hendrik Dienemann, Erich Hecker, Birte Schwarz, Clemens Aigner, Rudolf Hatz, Diana Lütke Brintrup, Karl-Heinz Jöckel, S Eggeling, Bernward Passlick, and Claudia Ose
Subjects: Adult, Male, 0301 basic medicine, Pulmonary and Respiratory Medicine, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Medizin, TNM staging system, Perioperative Care, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Carcinoma, Non-Small-Cell Lung, medicine, Humans, In patient, Prospective Studies, Stage (cooking), Pneumonectomy, Lung cancer, Aged, Neoplasm Staging, Aged, 80 and over, Lung, business.industry, Perioperative, Middle Aged, medicine.disease, Tumor Burden, Surgery, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Quality of Life, Female, Non small cell, business
Abstract: For early stage non-small cell lung cancer (NSCLC) retrospective data of functionally compromised patients undergoing segmentectomy showed equal outcomes for perioperative complications and quality of life (QoL) compared with lobectomy patients. However no prospectively randomized data comparing patients eligible for both procedures are available.We conducted a prospective, randomized, multicenter phase III trial and investigated perioperative complications and QoL in patients with NSCLC stage IA (7th edition) undergoing segmentectomy versus lobectomy. The EORTC Questionnaire Core-30 (QLQ C-30) supplemented by thirteen-item lung cancer-specific module (LC13) was assessed before surgery, at discharge, 6 weeks, 3, 6 and 12 months post-surgery.108 patients with verified or suspected NSCLC up to 2 cm diameter were enrolled, whereby 54 were assigned to lobectomy and 54 to segmentectomy. Due to nodal disease, tumor size and surgical reasons estimated during the operation, eight patients of the segmentectomy group received a lobectomy. In hospital and 90 days mortality was 0% in both groups. Perioperative complications were observed in 6 (11.3%) patients after segmentectomy and in 8 patients (14.8%) after lobectomy (p = 0.563), while the 90-day morbidity were 17% and 25.9% (9 and 14 patients), respectively (p = 0.452). Twelve months after surgery, there was a significant deterioration to the baselines of physical (p 0.001) and cognitive functioning (p = 0.025), dyspnea (p 0.001) and fatigue (p = 0.003) in the lobectomy group. Dyspnea showed a faster recovery in the segmentectomy compared to lobectomy group with statistical significance (p = 0.016 after 12 months).In patients with early-stage NSCLC, segmentectomy is associated with a statistically not significant lower perioperative morbidity and appears to provide a superior recovery in QoL compared with lobectomy patients.
Published: 2019

11. Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author: Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Luxia Zhang, Young-Ho Khang, Ellina Rakhimova, Kairit Mikkel, Tiina Vlasoff, Eruke E. Egbagbe, Sidsel Graff-Iversen, Ilona Nenko, Magdalena Klimek, Mathilde Savy, Sanjib Kumar Sharma, Alfonso Siani, Luís Lopes, Vanina Bongard, Gregor Jurak, Jacqueline F. Price, Christina-Paulina Lambrinou, Maria Lc Iurilli, Rainford J. Wilks, Bontha V. Babu, Fereidoun Azizi, Harunobu Nakamura, Marialaura Bonaccio, Angela Döring, Zhenyu Zhang, Naser Ahmadi, Jolanta Słowikowska-Hilczer, Ana Paula Carlos Cândido, Clive Osmond, Thirunavukkarasu Sathish, Robert J. Adams, Themistoklis Tzotzas, Reina Engle-Stone, Atul Trivedi, Shoichiro Tsugane, Niels Møller, Jorge Bezerra, Dénes Molnár, Muhammad Fadhli Mohd Yusoff, Badreya Al-Lahou, J. Jaime Miranda, Bahram Mohajer, Sigmund A. Anderssen, Lital Keinan Boker, Eero Kajantie, Martin Gulliford, Maties Torrent, Sumit Bharadwaj, Toshiharu Ninomiya, Zbigniew Gaciong, Nayu Ikeda, Li Juan Wu, Adrian Richter, Licia Iacoviello, Marc J. Gunter, Wenbin Wei, Norsyamlina Che Abdul Rahim, Eman Aly, Ambady Ramachandran, Nils Lehmann, Soile E. Puhakka, Giovanni Veronesi, Hongsheng Bi, Eiji Oda, Jia Li Duan, Per Tynelius, José María Huerta, Janne Schurmann Tolstrup, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Hanno Ulmer, Shukri F. Mohamed, Anthony Kafatos, Suyeon Park, Mohsen Ibrahim, Hamed Pouraram, Bin Zhou, May Soe Aung, Lars Bo Andersen, Erfan Ghasemi, René Charles Sylva, Himanshu K. Chaturvedi, Luc Dauchet, Ahmad Ali Zainuddin, Angela Chetrit, Dan Zhu, Valérie Deschamps, Ko Ko Zaw, Peter Vollenweider, Tomas Vega, Yves Martin-Prével, Mahfuzar Rahman, Dorja Vočanec, Roman Topor-Madry, Vinay Nangia, Herculina S. Kruger, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Aleksander Giwercman, Elżbieta Dziankowska-Zaborszczyk, Cecilia Björkelund, Tatjana Hejgaard, Maria Puiu, Maria Benedetta Donati, Andrew Wong, Carlos P. Boissonnet, Santosh K. Bhargava, Patrick Kolsteren, Dermot O'Reilly, Bahareh Kheiri, Wolfgang Kratzer, Susanne R. de Rooij, H. Bas Bueno-de-Mesquita, Günther Fink, José R. Banegas, Michele Monroy-Valle, Drude Molbo, Mahmudur Rahman, Hynek Pikhart, Rafael N. Pichardo, Massimo Salvetti, Hui Cai, Sarah Filippi, Georg Posch, Hung-Kwan So, Yonghua Hu, Katsuyasu Kouda, Joana Carvalho, Gailute Bernotiene, Hannu Uusitalo, Thein Thein Htay, Felix Kaducu, Maigeng Zhou, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Michel Joffres, Sabina Zambon, Ronald D. Gregor, Vayia Rarra, Seyed Mohammad Hashemi-Shahri, Loreto Santa Marina, Galina Obreja, Rudolf Kaaks, Aya Mostafa, Maria do Carmo Franco, Beata Gurzkowska, Chien-Jen Chen, Marie Moitry, Nizal Sarrafzadegan, Xiangjun Wang, Diego Giulliano Destro Christofaro, Imperia Brajkovich, Fangfang Chen, Francesco Panza, Ling Yang, Holly E. Syddall, Cecily Kelleher, Michael Tornaritis, Ningli Wang, Lutgarde Thijs, Marjolein Visser, Angelika Schaffrath Rosario, María José Tormo, Jostein Steene-Johannessen, Norbert Amougou, Emmanuella Magriplis, Mar Alvarez-Pedrerol, Jingli Gao, Stig E. 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Magliano, Jitendra Jonnagaddala, Konstantinos Gkiouras, Paola Nardone, Alberto Barceló, Tomi-Pekka Tuomainen, Francesco Gianfagna, Stefania Maggi, Mohammad Hossein Somi, Behrooz Hamzeh, Miquel Porta, Vesna Jureša, Alexander D. Deev, David Faeh, Antonio Bernabe-Ortiz, Sirkka Keinänen-Kiukaanniemi, Ian Hambleton, Stefan Savin, Andre Pascal Kengne, R. Krishna Kumar, Kurt Widhalm, Marco M Ferrario, Parisa Amiri, Anjani Kumar Jha, Thamara Hubler Figueiró, Jana Kratenova, Claudia M. Hormiga, Maria Tsigga, Zivka Dika, Indrapal I. Meshram, Ei Ei K. Nang, Ian Rouse, Rusidah Selamat, Paul Korrovits, Grethe S. Tell, Julie Taylor, Anabela Mota-Pinto, Paolo Vineis, Kotsedi D Monyeki, Khuong Quynh Long, Frank J Rühli, Shelly R. McFarlane, Sara Santos Sanz, Edyta Łuszczki, Maria G. Stathopoulou, Tara Coppinger, Karin De Ridder, Lucie Viet, Anna Bugge, Mehdi Yaseri, Safiah Md Yusof, Sandra C. Fuchs, Muhammad Islam, Irfan Nuhoglu, Rui Providência, Bernard Maire, Leandra Abarca-Gómez, Sinead Brophy, Maria Ruiz-Castell, Daniela Pierannunzio, Cristina Taddei, Gowri Mahasampath, Gustavo Velasquez-Melendez, Hanna Tolonen, Sudhir Kowlessur, Bagher Larijani, Laura Torres-Collado, Susi Kriemler, Ali Akbar Shayesteh, Cynthia Robitaille, Jorge Escobedo-de la Peña, Yufang Bi, Chinh Nguyen Huu, Line Tang Møllehave, Vincent Jr DeGennaro, Noor Ani Ahmad, Anar Dushpanova, Agustinus Soemantri, Susana Sans, Ionela Pascanu, Gwenaëlle Le Coroller, Inger Ariansen, Kodanda R Kanala, Gert B. M. Mensink, Abhijit Sen, Sergej M. Ostojic, Hanan F. Abdul Rahim, Hélène Delisle, Francisco J. Félix-Redondo, Yadlapalli S. Kusuma, Michael Knoflach, Moein Yoosefi, Tanja G. M. Vrijkotte, Wolfgang Ahrens, Osvaldo Santos, Bethlehem D. Solomon, Erik Lykke Mortensen, Nikhil D. 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Aounallah-Skhiri , Joana Araújo , Inger Ariansen , Tahir Aris , Raphael E Arku , Nimmathota Arlappa , Krishna K Aryal , Thor Aspelund , Felix K Assah , Maria Cecília F Assunção , May Soe Aung , Juha Auvinen , Mária Avdicová , Shina Avi , Ana Azevedo , Mohsen Azimi-Nezhad , Fereidoun Azizi , Mehrdad Azmin , Bontha V Babu , Maja Bæksgaard Jørgensen , Azli Baharudin , Suhad Bahijri , Jennifer L Baker , Nagalla Balakrishna , Mohamed Bamoshmoosh , Maciej Banach , Piotr Bandosz , José R Banegas , Joanna Baran , Barbagallo CM, Alberto Barceló , Amina Barkat , Aluisio Jd Barros , Mauro Virgílio Gomes Barros , Abdul Basit , Joao Luiz D Bastos , Iqbal Bata , Anwar M Batieha , Rosangela L Batista , Zhamilya Battakova , Assembekov Batyrbek , Louise A Baur , Robert Beaglehole , Silvia Bel-Serrat , Antonisamy Belavendra , Habiba Ben Romdhane , Judith Benedics , Mikhail Benet , Ingunn Holden Bergh , Salim Berkinbayev , Antonio Bernabe-Ortiz , Gailute Bernotiene , Heloísa Bettiol , Jorge Bezerra , Aroor Bhagyalaxmi , Sumit Bharadwaj , Santosh K Bhargava , Zulfiqar A Bhutta , Hongsheng Bi , Yufang Bi , Daniel Bia , Elysée Claude Bika Lele, Mukharram M Bikbov , Bihungum Bista , Dusko J Bjelica , Peter Bjerregaard , Espen Bjertness , Marius B Bjertness , Cecilia Björkelund , Katia V Bloch , Anneke Blokstra , Simona Bo , Martin Bobak , Lynne M Boddy , Bernhard O Boehm , Heiner Boeing , Jose G Boggia , Elena Bogova , Carlos P Boissonnet , Stig E Bojesen , Marialaura Bonaccio , Vanina Bongard , Alice Bonilla-Vargas , Matthias Bopp , Herman Borghs , Lien Braeckevelt , Lutgart Braeckman , Marjolijn Ce Bragt , Imperia Brajkovich , Francesco Branca , Juergen Breckenkamp , João Breda , Hermann Brenner , Lizzy M Brewster , Garry R Brian , Lacramioara Brinduse , Sinead Brophy , Graziella Bruno , H Bas Bueno-de-Mesquita , Anna Bugge , Marta Buoncristiano , Genc Burazeri , Con Burns , Antonio Cabrera de León , Joseph Cacciottolo , Hui Cai , Tilema Cama , Christine Cameron , José Camolas , 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Cottel , Chris Cowell , Cora L Craig , Amelia C Crampin , Ana B Crujeiras , Semánová Csilla , Alexandra M Cucu , Liufu Cui , Felipe V Cureau , Ewelina Czenczek-Lewandowska , Graziella D'Arrigo , Eleonora d'Orsi , Liliana Dacica , María Ángeles Dal Re Saavedra , Jean Dallongeville , Camilla T Damsgaard , Rachel Dankner , Thomas M Dantoft , Parasmani Dasgupta , Saeed Dastgiri , Luc Dauchet , Kairat Davletov , Guy De Backer , Dirk De Bacquer , Giovanni de Gaetano , Stefaan De Henauw , Paula Duarte de Oliveira , David De Ridder , Karin De Ridder , Susanne R de Rooij , Delphine De Smedt , Mohan Deepa , Alexander D Deev , Vincent Jr DeGennaro , Abbas Dehghan , Hélène Delisle , Francis Delpeuch , Stefaan Demarest , Elaine Dennison , Katarzyna Dereń , Valérie Deschamps , Meghnath Dhimal , Augusto F Di Castelnuovo , Juvenal Soares Dias-da-Costa , María Elena Díaz-Sánchez , Alejandro Diaz , Zivka Dika , Shirin Djalalinia , Visnja Djordjic , Ha Tp Do , Annette J Dobson , Maria Benedetta Donati , 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, Daniel Fernández-Bergés , Daniel Ferrante , Thomas Ferrao , Marika Ferrari , Marco M Ferrario , Catterina Ferreccio , Eldridge Ferrer , Jean Ferrieres , Thamara Hubler Figueiró , Anna Fijalkowska , Günther Fink , Krista Fischer , Leng Huat Foo , Maria Forsner , Heba M Fouad , Damian K Francis , Maria do Carmo Franco , Ruth Frikke-Schmidt , Guillermo Frontera , Flavio D Fuchs , Sandra C Fuchs , Isti I Fujiati , Yuki Fujita , Matsuda Fumihiko , Takuro Furusawa , Zbigniew Gaciong , Mihai Gafencu , Andrzej Galbarczyk , Henrike Galenkamp , Daniela Galeone , Myriam Galfo , Fabio Galvano , Jingli Gao , Manoli Garcia-de-la-Hera , Marta García-Solano , Dickman Gareta , Sarah P Garnett , Jean-Michel Gaspoz , Magda Gasull , Adroaldo Cesar Araujo Gaya , Anelise Reis Gaya , Andrea Gazzinelli , Ulrike Gehring , Harald Geiger , Johanna M Geleijnse , Ali Ghanbari , Erfan Ghasemi , Oana-Florentina Gheorghe-Fronea , Simona Giampaoli , Francesco Gianfagna , Tiffany K Gill , Jonathan Giovannelli , Glen Gironella , Aleksander Giwercman , Konstantinos Gkiouras , Justyna Godos , Sibel Gogen , Marcel Goldberg , Rebecca A Goldsmith , David Goltzman , Santiago F Gómez , Aleksandra Gomula , Bruna Goncalves Cordeiro da Silva , Helen Gonçalves , David A Gonzalez-Chica , Marcela Gonzalez-Gross , Margot González-Leon , Juan P González-Rivas , Clicerio González-Villalpando , María-Elena González-Villalpando , Angel R Gonzalez , Frederic Gottrand , Antonio Pedro Graça , Sidsel Graff-Iversen , Dušan Grafnetter , Aneta Grajda , Maria G Grammatikopoulou , Ronald D Gregor , Tomasz Grodzicki , Else Karin Grøholt , Anders Grøntved , Giuseppe Grosso , Gabriella Gruden , Dongfeng Gu , Emanuela Gualdi-Russo , Pilar Guallar-Castillón , Andrea Gualtieri , Elias F Gudmundsson , Vilmundur Gudnason , Ramiro Guerrero , Idris Guessous , Andre L Guimaraes , Martin C Gulliford , Johanna Gunnlaugsdottir , Marc J Gunter , Xiu-Hua Guo , Yin Guo , Prakash C Gupta , Rajeev Gupta , Oye Gureje , Beata Gurzkowska , 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Huiart , Constanta Huidumac Petrescu , Martijn Huisman , Abdullatif Husseini , Chinh Nguyen Huu , Inge Huybrechts , Nahla Hwalla , Jolanda Hyska , Licia Iacoviello , Jesús M Ibarluzea , Mohsen M Ibrahim , Norazizah Ibrahim Wong , M Arfan Ikram , Violeta Iotova , Vilma E Irazola , Takafumi Ishida , Muhammad Islam , Sheikh Mohammed Shariful Islam , Masanori Iwasaki , Jeremy M Jacobs , Hashem Y Jaddou , Tazeen Jafar , Kenneth James , Kazi M Jamil , Konrad Jamrozik , Imre Janszky , Edward Janus , Juel Jarani , Marjo-Riitta Jarvelin , Grazyna Jasienska , Ana Jelakovic , Bojan Jelakovic , Garry Jennings , Anjani Kumar Jha , Chao Qiang Jiang , Ramon O Jimenez , Karl-Heinz Jöckel , Michel Joffres , Mattias Johansson , Jari J Jokelainen , Jost B Jonas , Jitendra Jonnagaddala , Torben Jørgensen , Pradeep Joshi , Farahnaz Joukar , Dragana P Jovic , Jacek J Jóźwiak , Anne Juolevi , Gregor Jurak , Iulia Jurca Simina , Vesna Juresa , Rudolf Kaaks , Felix O Kaducu , Anthony Kafatos , Eero O Kajantie , Zhanna Kalmatayeva , Ofra Kalter-Leibovici , Yves Kameli , Freja B Kampmann , Kodanda R Kanala , Srinivasan Kannan , Efthymios Kapantais , Argyro Karakosta , Line L Kårhus , Khem B Karki , Marzieh Katibeh , Joanne Katz , Peter T Katzmarzyk , Jussi Kauhanen , Prabhdeep Kaur , Maryam Kavousi , Gyulli M Kazakbaeva , Ulrich Keil , Lital Keinan Boker , Sirkka Keinänen-Kiukaanniemi , Roya Kelishadi , Cecily Kelleher , Han Cg Kemper , Andre P Kengne , Maryam Keramati , Alina Kerimkulova , Mathilde Kersting , Timothy Key , Yousef Saleh Khader , Davood Khalili , Kay-Tee Khaw , Bahareh Kheiri , Motahareh Kheradmand , Alireza Khosravi , Ilse Msl Khouw , Ursula Kiechl-Kohlendorfer , Stefan Kiechl , Japhet Killewo , Dong Wook Kim , Hyeon Chang Kim , Jeongseon Kim , Jenny M Kindblom , Heidi Klakk , Magdalena Klimek , Jeannette Klimont , Jurate Klumbiene , Michael Knoflach , Bhawesh Koirala , Elin Kolle , Patrick Kolsteren , Jürgen König , Raija Korpelainen , Paul Korrovits , Magdalena Korzycka , 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, Yves Martin-Prevel , Rosemarie Martin , Reynaldo Martorell , Eva Martos , Katharina Maruszczak , Stefano Marventano , Luis P Mascarenhas , Shariq R Masoodi , Ellisiv B Mathiesen , Prashant Mathur , Alicia Matijasevich , Tandi E Matsha , Christina Mavrogianni , Artur Mazur , Jean Claude N Mbanya , Shelly R McFarlane , Stephen T McGarvey , Martin McKee , Stela McLachlan , Rachael M McLean , Scott B McLean , Breige A McNulty , Sounnia Mediene Benchekor , Jurate Medzioniene , Parinaz Mehdipour , Kirsten Mehlig , Amir Houshang Mehrparvar , Aline Meirhaeghe , Jørgen Meisfjord , Christa Meisinger , Ana Maria B Menezes , Geetha R Menon , Gert Bm Mensink , Maria Teresa Menzano , Alibek Mereke , Indrapal I Meshram , Andres Metspalu , Haakon E Meyer , Jie Mi , Kim F Michaelsen , Nathalie Michels , Kairit Mikkel , Karolina Milkowska , Jody C Miller , Cláudia S Minderico , G K Mini , Juan Francisco Miquel , Mohammad Reza Mirjalili , Daphne Mirkopoulou , Erkin Mirrakhimov , Marjeta 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Theodoridis , Lutgarde Thijs , Nihal Thomas , Betina H Thuesen , Lubica Tichá , Erik J Timmermans , Anne Tjonneland , Hanna K Tolonen , Janne S Tolstrup , Murat Topbas , Roman Topór-Madry , Liv Elin Torheim , María José Tormo , Michael J Tornaritis , Maties Torrent , Laura Torres-Collado , Stefania Toselli , Giota Touloumi , Pierre Traissac , Thi Tuyet-Hanh Tran , Dimitrios Trichopoulos , Antonia Trichopoulou , Oanh Th Trinh , Atul Trivedi , Lechaba Tshepo , Maria Tsigga , Shoichiro Tsugane , Azaliia M Tuliakova , Marshall K Tulloch-Reid , Fikru Tullu , Tomi-Pekka Tuomainen , Jaakko Tuomilehto , Maria L Turley , Gilad Twig , Per Tynelius , Themistoklis Tzotzas , Christophe Tzourio , Peter Ueda , Eunice Ugel , Flora Am Ukoli , Hanno Ulmer , Belgin Unal , Zhamyila Usupova , Hannu Mt Uusitalo , Nalan Uysal , Justina Vaitkeviciute , Gonzalo Valdivia , Susana Vale , Damaskini Valvi , Rob M van Dam , Johan Van der Heyden , Yvonne T van der Schouw , Koen Van Herck , Hoang Van Minh , Natasja M Van Schoor , Irene Gm van Valkengoed , Dirk Vanderschueren , Diego Vanuzzo , Anette Varbo , Gregorio Varela-Moreiras , Patricia Varona-Pérez , Senthil K Vasan , Tomas Vega , Toomas Veidebaum , Gustavo Velasquez-Melendez , Biruta Velika , Giovanni Veronesi , Wm Monique Verschuren , Cesar G Victora , Giovanni Viegi , Lucie Viet , Salvador Villalpando , Paolo Vineis , Jesus Vioque , Jyrki K Virtanen , Marjolein Visser , Sophie Visvikis-Siest , Bharathi Viswanathan , Mihaela Vladulescu , Tiina Vlasoff , Dorja Vocanec , Peter Vollenweider , Henry Völzke , Ari Voutilainen , Sari Voutilainen , Martine Vrijheid , Tanja Gm Vrijkotte , Alisha N Wade , Aline Wagner , Thomas Waldhör , Janette Walton , Elvis Oa Wambiya , Wan Mohamad Wan Bebakar , Wan Nazaimoon Wan Mohamud , Rildo de Souza Wanderley Júnior , Ming-Dong Wang , Ningli Wang , Qian Wang , Xiangjun Wang , Ya Xing Wang , Ying-Wei Wang , S Goya Wannamethee , Nicholas Wareham , Adelheid Weber , Niels Wedderkopp , Deepa Weerasekera , Daniel Weghuber , Wenbin Wei , Aneta Weres , Bo Werner , Peter H Whincup , Kurt Widhalm , Indah S Widyahening , Andrzej Wiecek , Rainford J Wilks , Johann Willeit , Peter Willeit , Julianne Williams , Tom Wilsgaard , Bogdan Wojtyniak , Roy A Wong-McClure , Andrew Wong , Jyh Eiin Wong , Tien Yin Wong , Jean Woo , Mark Woodward , Frederick C Wu , Jianfeng Wu , Li Juan Wu , Shouling Wu , Haiquan Xu , Liang Xu , Nor Azwany Yaacob , Uruwan Yamborisut , Weili Yan , Ling Yang , Xiaoguang Yang , Yang Yang , Nazan Yardim , Mehdi Yaseri , Tabara Yasuharu , Xingwang Ye , Panayiotis K Yiallouros , Moein Yoosefi , Akihiro Yoshihara , Qi Sheng You , San-Lin You , Novie O Younger-Coleman , Safiah Md Yusof , Ahmad Faudzi Yusoff , Luciana Zaccagni , Vassilis Zafiropulos , Ahmad A Zainuddin , Seyed Rasoul Zakavi , Farhad Zamani , Sabina Zambon , Antonis Zampelas , Hana Zamrazilová , Maria Elisa Zapata , Abdul Hamid Zargar , Ko Ko Zaw , Tomasz Zdrojewski , Kristyna Zejglicova , Tajana Zeljkovic Vrkic , Yi Zeng , Luxia Zhang , Zhen-Yu Zhang , Dong Zhao , Ming-Hui Zhao , Wenhua Zhao , Shiqi Zhen , Wei Zheng , Yingfeng Zheng , Bekbolat Zholdin , Maigeng Zhou , Dan Zhu , Marie Zins , Emanuel Zitt , Yanina Zocalo , Julio Zuñiga Cisneros , Monika Zuziak , Majid Ezzati , Sarah Filippi, Epidemiology, Iurilli, Maria LC, Zhou, Bin, Bennett, James E, Carrillo-Larco, Rodrigo M, Sophiea, Marisa K, Rodriguez-Martinez, Andrea, Bixby, Honor, Solomon, Bethlehem D, Taddei, Cristina, Danaei, Goodarz, Di Cesare, Mariachiara, Stevens, Gretchen A, Riley, Leanne M, Savin, Stefan, Cowan, Melanie J, Bovet, Pascal, Damasceno, Albertino, Chirita-Emandi, Adela, Hayes, Alison J, Ikeda, Nayu, Jackson, Rod T, Khang, Young-Ho, Laxmaiah, Avula, Liu, Jing, Miranda, J Jaime, Saidi, Olfa, Sebert, Sylvain, Sorić, Maroje, Starc, Gregor, Gregg, Edward W, Abarca-Gómez, Leandra, Abdeen, Ziad A, Abdrakhmanova, Shynar, Ghaffar, Suhaila Abdul, Rahim, Hanan F Abdul, Abu-Rmeileh, Niveen M, Garba, Jamila Abubakar, Acosta-Cazares, 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Mohebbi, Iraj, Mohebi, Farnam, Moitry, Marie, Molbo, Drude, Møllehave, Line T, Møller, Niels C, Molnár, Déne, Momenan, Amirabba, Mondo, Charles K, Monroy-Valle, Michele, Monterrubio-Flores, Eric, Monyeki, Kotsedi Daniel K, Moon, Jin Soo, Moosazadeh, Mahmood, Moreira, Leila B, Morejon, Alain, Moreno, Luis A, Morgan, Karen, Morin, Suzanne N, Mortensen, Erik Lykke, Moschonis, George, Mossakowska, Malgorzata, Mostafa, Aya, Mota-Pinto, Anabela, Mota, Jorge, Motlagh, Mohammad Esmaeel, Motta, Jorge, Moura-dos-Santos, Marcos André, Mridha, Malay K, Msyamboza, Kelias P, Mu, Thet Thet, Muc, Magdalena, Mugoša, Boban, Muiesan, Maria L, Mukhtorova, Parvina, Müller-Nurasyid, Martina, Murphy, Neil, Mursu, Jaakko, Murtagh, Elaine M, Musa, Kamarul Imran, Milanovic, Sanja Music, Musil, Vera, Mustafa, Norlaila, Nabipour, Iraj, Naderimagham, Shohreh, Nagel, Gabriele, Naidu, Balkish M, Najafi, Farid, Nakamura, Harunobu, Námešná, Jana, Ei K Nang, Ei, Nangia, Vinay B, Nankap, Martin, Narake, Sameer, Nardone, Paola, Nauck, Matthia, Neal, William A, Nejatizadeh, Azim, Nekkantti, Chandini, Nelis, Keiu, Nelis, Lii, Nenko, Ilona, Neovius, Martin, Nervi, Flavio, Nguyen, Chung T, Nguyen, Nguyen D, Nguyen, Quang Ngoc, Nieto-Martínez, Ramfis E, Nikitin, Yury P, Ning, Guang, Ninomiya, Toshiharu, Nishtar, Sania, Noale, Marianna, Noboa, Oscar A, Nogueira, Helena, Norat, Teresa, Nordendahl, Maria, Nordestgaard, Børge G, Noto, Davide, Nowak-Szczepanska, Natalia, Al Nsour, Mohannad, Nuhoglu, Irfan, Nurk, Eha, O'Neill, Terence W, O'Reilly, Dermot, Obreja, Galina, Ochimana, Caleb, Ochoa-Avilés, Angélica M, Oda, Eiji, Oh, Kyungwon, Ohara, Kumiko, Ohlsson, Clae, Ohtsuka, Ryutaro, Olafsson, Örn, Olinto, Maria Teresa A, Oliveira, Isabel O, Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M, Ordunez, Pedro, Ornelas, Rui, Ortiz, Ana P, Ortiz, Pedro J, Osler, Merete, Osmond, Clive, Ostojic, Sergej M, Ostovar, Afshin, Otero, Johanna A, Overvad, Kim, Owusu-Dabo, Elli, Paccaud, Fred Michel, Padez, Cristina, Pagkalos, Ioanni, Pahomova, Elena, de Paiva, Karina Mary, Pajak, Andrzej, Palli, Domenico, Palloni, Alberto, Palmieri, Luigi, Pan, Wen-Harn, Panda-Jonas, Songhomitra, Pandey, Arvind, Panza, Francesco, Papandreou, Dimitrio, Park, Soon-Woo, Park, Suyeon, Parnell, Winsome R, Parsaeian, Mahboubeh, Pascanu, Ionela M, Pasquet, Patrick, Patel, Nikhil D, Pecin, Ivan, Pednekar, Mangesh S, Peer, Nasheeta, Pei, Gao, Peixoto, Sergio Viana, Peltonen, Markku, Pereira, Alexandre C, Peres, Marco A, Pérez-Farinós, Napoleón, Pérez, Cynthia M, Peterkova, Valentina, Peters, Annette, Petersmann, Astrid, Petkeviciene, Janina, Petrauskiene, Ausra, Pettenuzzo, Emanuela, Peykari, Niloofar, Pham, Son Thai, Pichardo, Rafael N, Pierannunzio, Daniela, Pigeot, Iri, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pistelli, Francesco, Pitakaka, Freda, Piwonska, Aleksandra, Pizarro, Andreia N, Plans-Rubió, Pedro, Poh, Bee Koon, Pohlabeln, Hermann, Pop, Raluca M, Popovic, Stevo R, Porta, Miquel, Posch, Georg, Poudyal, Anil, Poulimeneas, Dimitrio, Pouraram, Hamed, Pourfarzi, Farhad, Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Price, Alison J, Price, Jacqueline F, Providencia, Rui, Puder, Jardena J, Pudule, Iveta, Puhakka, Soile E, Puiu, Maria, Punab, Margu, Qasrawi, Radwan F, Qorbani, Mostafa, Bao, Tran Quoc, Radic, Ivana, Radisauskas, Ricarda, Rahimikazerooni, Salar, Rahman, Mahfuzar, Rahman, Mahmudur, Raitakari, Olli, Raj, Manu, Rakhimova, Ellina, Rakhmatulloev, Sherali, Rakovac, Ivo, Rao, Sudha Ramachandra, Ramachandran, Ambady, Ramke, Jacqueline, Ramos, Elisabete, Ramos, Rafel, Rampal, Lekhraj, Rampal, Sanjay, Rarra, Vayia, Rascon-Pacheco, Ramon A, Rasmussen, Mette, Rech, Cassiano Ricardo, Redon, Josep, Reganit, Paul Ferdinand M, Regecová, Valéria, Revilla, Lui, Rezaianzadeh, Abba, Ribas-Barba, Lourde, Ribeiro, Robespierre, Riboli, Elio, Richter, Adrian, Rigo, Fernando, Rinaldo, Natascia, de Wit, Tobias F Rinke, Rito, Ana, Ritti-Dias, Raphael M, Rivera, Juan A, Robitaille, Cynthia, Roccaldo, Romana, Rodrigues, Daniela, Rodríguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, María, Rodríguez-Villamizar, Laura A, Roggenbuck, Ulla, Rojas-Martinez, Rosalba, Rojroongwasinkul, Nipa, Romaguera, Dora, Romeo, Elisabetta L, Rosario, Rafaela V, Rosengren, Annika, Rouse, Ian, Roy, Joel GR, Rubinstein, Adolfo, Rühli, Frank J, Ruidavets, Jean-Bernard, Ruiz-Betancourt, Blanca Sandra, Ruiz-Castell, Maria, Moreno, Emma Ruiz, Rusakova, Iuliia A, Jonsson, Kenisha Russell, Russo, Paola, Rust, Petra, Rutkowski, Marcin, Sabanayagam, Charumathi, Sacchini, Elena, Sachdev, Harshpal S, Sadjadi, Alireza, Safarpour, Ali Reza, Safiri, Saeid, Saki, Nader, Salanave, Benoit, Martinez, Eduardo Salazar, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Samoutian, Margarita, Sánchez-Abanto, Jose, Sandjaja, null, Sans, Susana, Marina, Loreto Santa, Santos, Diana A, Santos, Ina S, Santos, Lèlita C, Santos, Maria Paula, Santos, Osvaldo, Santos, Rute, Sanz, Sara Santo, Saramies, Jouko L, Sardinha, Luis B, Sarrafzadegan, Nizal, Sathish, Thirunavukkarasu, Saum, Kai-Uwe, Savva, Savva, Savy, Mathilde, Sawada, Norie, Sbaraini, Mariana, Scazufca, Marcia, Schaan, Beatriz D, Rosario, Angelika Schaffrath, Schargrodsky, Herman, Schienkiewitz, Anja, Schipf, Sabine, Schmidt, Carsten O, Schmidt, Ida Maria, Schnohr, Peter, Schöttker, Ben, Schramm, Sara, Schramm, Stine, Schröder, Helmut, Schultsz, Constance, Schutte, Aletta E, Sein, Aye Aye, Selamat, Rusidah, Sember, Vedrana, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Sequera, Victor, Serra-Majem, Lui, Servais, Jennifer, Ševcíková, Ludmila, Shalnova, Svetlana A, Shamah-Levy, Teresa, Shamshirgaran, Morteza, Shanthirani, Coimbatore Subramaniam, Sharafkhah, Maryam, Sharma, Sanjib K, Shaw, Jonathan E, Shayanrad, Amaneh, Shayesteh, Ali Akbar, Shengelia, Lela, Shi, Zumin, Shibuya, Kenji, Shimizu-Furusawa, Hana, Shin, Dong Wook, Shirani, Majid, Shiri, Rahman, Shrestha, Namuna, Si-Ramlee, Khairil, Siani, Alfonso, Siantar, Rosalynn, Sibai, Abla M, Silva, Antonio M, Silva, Diego Augusto Santo, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöberg, Agneta, Sjöström, Michael, Skodje, Gry, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, So, Hung-Kwan, Soares, Fernanda Cunha, Sobek, Grzegorz, Sobngwi, Eugène, Sodemann, Morten, Söderberg, Stefan, Soekatri, Moesijanti YE, Soemantri, Agustinu, Sofat, Reecha, Solfrizzi, Vincenzo, Somi, Mohammad Hossein, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild IA, Sørgjerd, Elin P, Jérome, Charles Sossa, Soto-Rojas, Victoria E, Soumaré, Aïcha, Sovic, Slavica, Sparboe-Nilsen, Bente, Sparrenberger, Karen, Spinelli, Angela, Spiroski, Igor, Staessen, Jan A, Stamm, Hanspeter, Stathopoulou, Maria G, Staub, Kaspar, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stevanovic, Ranko, Stieber, Jutta, Stöckl, Dori, Stocks, Tanja, Stokwiszewski, Jakub, Stoyanova, Ekaterina, Stratton, Gareth, Stronks, Karien, Strufaldi, Maria Wany, Sturua, Lela, Suárez-Medina, Ramón, Suka, Machi, Sun, Chien-An, Sundström, Johan, Sung, Yn-Tz, Sunyer, Jordi, Suriyawongpaisal, Paibul, Swinburn, Boyd A, Sy, Rody G, Syddall, Holly E, Sylva, René Charle, Szklo, Moyse, Szponar, Lucjan, Tai, E Shyong, Tammesoo, Mari-Lii, Tamosiunas, Abdona, Tan, Eng Joo, Tang, Xun, Tanrygulyyeva, Maya, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarp, Jakob, Tarqui-Mamani, Carolina B, Braunerová, Radka Taxová, Taylor, Anne, Taylor, Julie, Tchibindat, Félicité, Tebar, William R, Tell, Grethe S, Tello, Tania, Tham, Yih Chung, Thankappan, KR, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thomas, Nihal, Thuesen, Betina H, Tichá, Lubica, Timmermans, Erik J, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Torheim, Liv Elin, Tormo, María José, Tornaritis, Michael J, Torrent, Matie, Torres-Collado, Laura, Toselli, Stefania, Touloumi, Giota, Traissac, Pierre, Tran, Thi Tuyet-Hanh, Trichopoulos, Dimitrio, Trichopoulou, Antonia, Trinh, Oanh TH, Trivedi, Atul, Tshepo, Lechaba, Tsigga, Maria, Tsugane, Shoichiro, Tuliakova, Azaliia M, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Twig, Gilad, Tynelius, Per, Tzotzas, Themistokli, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice, Ukoli, Flora AM, Ulmer, Hanno, Unal, Belgin, Usupova, Zhamyila, Uusitalo, Hannu MT, Uysal, Nalan, Vaitkeviciute, Justina, Valdivia, Gonzalo, Vale, Susana, Valvi, Damaskini, van Dam, Rob M, Van der Heyden, Johan, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, Van Schoor, Natasja M, van Valkengoed, Irene GM, Vanderschueren, Dirk, Vanuzzo, Diego, Varbo, Anette, Varela-Moreiras, Gregorio, Varona-Pérez, Patricia, Vasan, Senthil K, Vega, Toma, Veidebaum, Tooma, Velasquez-Melendez, Gustavo, Velika, Biruta, Veronesi, Giovanni, Verschuren, WM Monique, Victora, Cesar G, Viegi, Giovanni, Viet, Lucie, Villalpando, Salvador, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visser, Marjolein, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vladulescu, Mihaela, Vlasoff, Tiina, Vocanec, Dorja, Vollenweider, Peter, Völzke, Henry, Voutilainen, Ari, Voutilainen, Sari, Vrijheid, Martine, Vrijkotte, Tanja GM, Wade, Alisha N, Wagner, Aline, Waldhör, Thoma, Walton, Janette, Wambiya, Elvis OA, Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, de Souza Wanderley Júnior, Rildo, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Weber, Adelheid, Wedderkopp, Niel, Weerasekera, Deepa, Weghuber, Daniel, Wei, Wenbin, Weres, Aneta, Werner, Bo, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Julianne, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Andrew, Wong, Jyh Eiin, Wong, Tien Yin, Woo, Jean, Woodward, Mark, Wu, Frederick C, Wu, Jianfeng, Wu, Li Juan, Wu, Shouling, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yamborisut, Uruwan, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yardim, Nazan, Yaseri, Mehdi, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K, Yoosefi, Moein, Yoshihara, Akihiro, You, Qi Sheng, You, San-Lin, Younger-Coleman, Novie O, Md Yusof, Safiah, Yusoff, Ahmad Faudzi, Zaccagni, Luciana, Zafiropulos, Vassili, Zainuddin, Ahmad A, Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antoni, Zamrazilová, Hana, Zapata, Maria Elisa, Zargar, Abdul Hamid, Ko Zaw, Ko, Zdrojewski, Tomasz, Zejglicova, Kristyna, Vrkic, Tajana Zeljkovic, Zeng, Yi, Zhang, Luxia, Zhang, Zhen-Yu, Zhao, Dong, Zhao, Ming-Hui, Zhao, Wenhua, Zhen, Shiqi, Zheng, Wei, Zheng, Yingfeng, Zholdin, Bekbolat, Zhou, Maigeng, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Cisneros, Julio Zuñiga, Zuziak, Monika, Ezzati, Majid, Filippi, Sarah, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: Population -- Health aspects, Leanness, Baixo peso/Underweight, none, Double burden, alipainoisuus, tulotaso, global health, systematic analysis, Sedentary behaviors, RC1200, Prospective associations, 0302 clinical medicine, underweight, nälänhätä, Biology (General), skin and connective tissue diseases, Children, ComputingMilieux_MISCELLANEOUS, Body mass index, Human Nutrition & Health, education.field_of_study, Humane Voeding & Gezondheid, ylipaino, General Medicine, kansainvälinen vertailu, 3. Good health, World health, Medicine, A100 Pre-clinical Medicine, Population distribution, medicine.medical_specialty, QH301-705.5, Science, Socio-culturale, Nursing, Social sciences, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Thinness, SDG 3 - Good Health and Well-being, BMI, epidemiology, obesity, None, Humans, Obesidade/Obesity, SDG 2 - Zero Hunger, education, VLAG, US adults, Omvårdnad, body mass index, malnutrition, obesity, underweight, nutritional and metabolic diseases, medicine.disease, terveellisyys, Obesity, Faculdade de Ciências Sociais, Body Mass Index, Prevalence, Risk Factors, General Biochemistry, WIAS, lihavuus, RA, Demography, N.A, double burden, Settore MED/09 - Medicina Interna, alueelliset erot, Nutrition and Disease, Animal Nutrition, [SDV]Life Sciences [q-bio], Medizin, 030204 cardiovascular system & hematology, 0601 Biochemistry and Cell Biology, Change distribution of body mass index, RA0421, Voeding en Ziekte, Epidemiology, Medicine and Health Sciences, Global health, Índice de massa corporal/Body Mass Index, 030212 general & internal medicine, Underweight, painoindeksi, 2. Zero hunger, General Neuroscience, aliravitsemus, elintarvikkeet, health, Public Health, Global Health, Social Medicine and Epidemiology, Diervoeding, 3142 Public health care science, environmental and occupational health, purl.org/pe-repo/ocde/ford#3.01.03 [https], Chinese adults, pooled analysis, medicine.symptom, Diet quality, B120 Physiology, Research Article, trends, purl.org/pe-repo/ocde/ford#1.06.03 [https], prevalence, Population, Mothers, Genetics and Molecular Biology, 3121 Internal medicine, medicine, Life Science, ddc:610, 3125 Otorhinolaryngology, ophthalmology, kehonkoostumus, Nutrition, Australian adults, General Immunology and Microbiology, purl.org/pe-repo/ocde/ford#3.01.04 [https], Ciências sociais, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Malnutrition, Epidemiology and Global Health, sense organs, Estilos de Vida e Impacto na Saúde
Abstract: From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions., Wellcome Trust, Medical Research Council, peer-reviewed
Published: 2021

12. Survival of patients with chronic lymphocytic leukemia before and after the introduction of chemoimmunotherapy in Germany

Author: Laura Khil, Can Zhang, Karl-Heinz Jöckel, Anna-Maria Fink, Andreas Stang, I. Wellmann, Hiltraud Kajüter, and Michael Hallek
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Adolescent, Epidemiology, Chronic lymphocytic leukemia, Medizin, Ofatumumab, Antibodies, Monoclonal, Humanized, Article, Disease-Free Survival, chemistry.chemical_compound, Chemoimmunotherapy, Obinutuzumab, immune system diseases, Internal medicine, hemic and lymphatic diseases, Germany, medicine, Humans, Registries, RC254-282, Aged, Retrospective Studies, Relative survival, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Hematology, Middle Aged, medicine.disease, Prognosis, Leukemia, Lymphocytic, Chronic, B-Cell, Cancer registry, Survival Rate, Leukemia, chemistry, Rituximab, Female, business, medicine.drug, Follow-Up Studies
Abstract: Chronic lymphocytic leukemia (CLL) is the most common leukemia of adults in western countries. Therapy is indicated in symptomatic and advanced stages and has changed fundamentally since 2010 when rituximab, an anti-CD20 antibody, has been approved for treatment of CLL. Until then therapy had been based on chemotherapy drugs. This study investigates whether survival in CLL patients improved at the population level after the introduction of combined chemoimmunotherapy. Data from the cancer registry North-Rhine Westphalia was used to calculate relative survival (RS) by applying period analyses. Age-standardized 5-year RS increased from 79% in 1998–2002 (75% in 2003–2007) to 81% in the calendar period 2008–2012 and 88% in 2013–2016 for men and continuously from 71% in 1998–2002 to 92% in 2013–2016 for women. In CLL patients aged 15–69 years 5-year RS increased from 83% to 90% for men and from 82% to 94% for women after adding an anti-CD20-antibody to chemotherapy while in the older age group of 70–79-year-old CLL patients an increase by 20 percentage points was observed. These findings show marked improvements in the survival of CLL patients at the population level subsequently to the approval of anti-CD 20 antibodies like rituximab, ofatumumab or obinutuzumab for CLL treatment.
Published: 2021

13. Impact of time to diagnosis on Mayo stages, treatment outcome, and survival in patients with AL amyloidosis and cardiac involvement

Author: Tienush Rassaf, Lukas Kessler, Ulrich Dührsen, Christoph Kimmich, Christoph Rischpler, Andreas Thimm, Jan Dürig, Hans Christian Reinhardt, Alexander Carpinteiro, Stefan Schönland, Tim Hagenacker, Karl-Heinz Jöckel, Eyad Naser, Maria Papathanasiou, Ute Hegenbart, Peter Luedike, and Sara Oubari
Subjects: Cardiac response, Adult, Male, medicine.medical_specialty, Delayed Diagnosis, Databases, Factual, Treatment outcome, Medizin, Antineoplastic Agents, Disease, Time-to-Treatment, Internal medicine, Surveys and Questionnaires, Antineoplastic Combined Chemotherapy Protocols, Overall survival, AL amyloidosis, Medicine, Humans, In patient, Medical history, Immunoglobulin Light-chain Amyloidosis, Aged, Retrospective Studies, Aged, 80 and over, Heart Failure, business.industry, Hematology, General Medicine, Middle Aged, medicine.disease, Prognosis, Survival Analysis, Treatment Outcome, Female, business, Time to diagnosis
Abstract: OBJECTIVE To study the impact of time to diagnosis on cardiac Mayo stages, treatment outcome, and overall survival. METHODS We retrospectively analyzed 77 consecutive patients diagnosed between 2015 and 2020 with AL amyloidosis and cardiac involvement. Medical history was recorded in standardized form with the help of a questionnaire. RESULTS Time from onset of symptoms of cardiac failure to diagnosis was correlated with the severity of cardiac involvement in modified Mayo 2004 and revised Mayo 2012 staging systems (rs = 0.30, 95% CI: 0.07-0.50, P = .007 and rs = 0.25, 95% CI: 0.01-0.45, P = .03). Patients with advanced Mayo 2004 stages received reduced-intensity regimens and had a lower probability to achieve adequate hematologic- and cardiac response after first-line treatment than patients with early stages (rs = 0.28, 95% CI: 0.04-0.48, P = .01 and rs = 0.72, 95% CI: 0.55-0.82, P
Published: 2021

14. Socioeconomic Position is Positively Associated with Monoclonal Gammopathy of Undetermined Significance in a Population-based Cohort Study

Author: Susanne Moebus, Jan Dürig, Ulrich Dührsen, Marina Arendt, Karl-Heinz Jöckel, Lewin Eisele, Elisabeth Debold, Nico Dragano, Mirjam Frank, Raimund Erbel, and Börge Schmidt
Subjects: Male, Population, Medizin, Logistic regression, Monoclonal Gammopathy of Undetermined Significance, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Risk Factors, immune system diseases, hemic and lymphatic diseases, Humans, Medicine, Prospective Studies, cardiovascular diseases, education, Aged, education.field_of_study, business.industry, Hematology, General Medicine, Odds ratio, Middle Aged, medicine.disease, Confidence interval, Socioeconomic Factors, 030220 oncology & carcinogenesis, Cohort, Etiology, Female, business, Body mass index, Monoclonal gammopathy of undetermined significance, Follow-Up Studies, 030215 immunology, Demography
Abstract: Knowledge of social inequalities in monoclonal gammopathy of undetermined significance (MGUS) will contribute to understanding multiple myeloma (MM) etiology, as MGUS consistently precedes MM. The aim of the present study was to examine whether socioeconomic position (SEP) is associated with MGUS in a population-based cohort including information on potential MGUS risk factors. Overall, 4787 study participants aged 45-75 years with information on MGUS were included. SEP indicators (education, income) and potential risk factors (i.e., body mass index, diabetes, smoking, dietary factors) were assessed at baseline. Overall, 260 MGUS cases were detected at baseline and prospectively over a 10-year follow-up. In age-adjusted logistic regression models, a lower chance of having MGUS at baseline or developing MGUS during 10 years of follow-up was indicated for groups of low SEP with odds ratios (OR) of 0.39 (95% confidence interval [95%-CI] 0.19-0.76) for women and 0.48 (95% CI 0.10-1.16) for men in the lowest compared to the highest educational group. After additionally including potential mediating risk factors in the regression models, the estimated ORs changed only slightly in magnitude. Similar results were obtained for income. Current smoking and low fruit consumption were associated with MGUS independently of SEP in women, but not in men. The present study indicates a lower MGUS risk in lower SEP groups. Supporting evidence is given that smoking and diet play a role in the development of MGUS independently of SEP, while it has to be assumed that risk factors unknown to date are responsible for the observed social inequalities in MGUS.
Published: 2019

15. CSF and blood Kallikrein-8: a promising early biomarker for Alzheimer’s disease

Author: Andreas Stang, Jan Rekowski, Markus Otto, Kathy Keyvani, Karl-Heinz Jöckel, Herrmann Esselmann, Hayrettin Tumani, Jonathan Vogelgsang, Sarah Teuber-Hanselmann, Christine A. F. von Arnim, Arne Herring, Kathrin Reetz, and Jens Wiltfang
Subjects: Male, Oncology, Parkinson's disease, affective disorders, Medizin, Neuropsychological Tests, 0302 clinical medicine, Blood serum, Cerebrospinal fluid, Kallikrein-8, 0303 health sciences, Area under the curve, Human brain, Middle Aged, Prognosis, 3. Good health, Psychiatry and Mental health, medicine.anatomical_structure, Disease Progression, biomarker, Biomarker (medicine), Female, Kallikreins, Alzheimer’s disease, medicine.medical_specialty, KLK8, psychiatric disease, tau Proteins, cerebrospinal fluid, 03 medical and health sciences, mild cognitive impairment, blood, Alzheimer Disease, Internal medicine, medicine, Humans, Dementia, Cognitive Dysfunction, ddc:610, Neurodegeneration, neuropsin, Aged, 030304 developmental biology, Amyloid beta-Peptides, Receiver operating characteristic, business.industry, Reproducibility of Results, medicine.disease, Cross-Sectional Studies, Parkinson’s disease, Surgery, Neurology (clinical), business, Biomarkers, 030217 neurology & neurosurgery
Abstract: ObjectiveThere is still an urgent need for supportive minimally invasive and cost-effective biomarkers for early diagnosis of Alzheimer’s disease (AD). Previous work in our lab has identified Kallikrein-8 (KLK8) as a potential candidate since it shows an excessive increase in human brain in preclinical disease stages. The aim of this study was to evaluate the diagnostic performance of cerebrospinal fluid (CSF) and blood KLK8 for AD and mild cognitive impairment (MCI) due to AD.MethodsIn this multi-centre trans-sectional study, clinical and laboratory data as well as CSF and/or blood serum samples of 237 participants, including 98 patients with mild AD, 21 with MCI due to AD and 118 controls were collected. CSF and/or serum KLK8 levels were analysed by ELISA. The diagnostic accuracy of KLK8 in CSF and blood was determined using receiver operating characteristic (ROC) analyses and compared with that of CSF core biomarkers Aβ42, P-tau and T-tau.ResultsThe diagnostic accuracy of CSF KLK8 was as good as that of core CSF biomarkers for AD (area under the curve (AUC)=0.89) and in case of MCI (AUC=0.97) even superior to CSF Aβ42. Blood KLK8 was a similarly strong discriminator for MCI (AUC=0.94) but slightly weaker for AD (AUC=0.83).ConclusionsThis is the first study to demonstrate the potential clinical utility of blood and CSF KLK8 as a biomarker for incipient AD. Future prospective validation studies are warranted.
Published: 2019

16. Natural language processing of German clinical colorectal cancer notes for guideline-based treatment evaluation

Author: Isabel Virchow, Matthias Becker, Britta Böckmann, Karl-Heinz Jöckel, and Stefan Kasper
Subjects: Male, 020205 medical informatics, Medizin, Health Informatics, 02 engineering and technology, computer.software_genre, Clinical decision support system, Terminology, 03 medical and health sciences, 0302 clinical medicine, Germany, 0202 electrical engineering, electronic engineering, information engineering, Electronic Health Records, Humans, Medicine, 030212 general & internal medicine, Medical diagnosis, Natural Language Processing, Retrospective Studies, business.industry, Gold standard, Unified Medical Language System, Cancer, Guideline, Middle Aged, medicine.disease, Information extraction, Practice Guidelines as Topic, Female, Artificial intelligence, Colorectal Neoplasms, business, computer, Algorithms, Software, Natural language processing
Abstract: Background Colorectal cancer is the most commonly occurring cancer in Germany, and the second and third most commonly diagnosed cancer in women and men, respectively. The therapy for this disease is based primarily on the tumor stages, which are usually documented in an unstructured form in medical information systems. In order to re-use this knowledge, the information must be extracted and annotated using the correct terminology. Methods In this study, a natural language processing pipeline is developed to identify specific guideline-based patient information and to annotate it with Unified Medical Language System concepts for manual evaluation by a physician. The gold standard for one-time evaluation is determined using the human abstraction of 2513 German clinical notes from electronic health records. Results Using this approach to process the narrative clinical notes on colorectal cancer for retrospective evaluation of the therapy recommendation, the algorithm achieves a precision value of 96.64% for tumor stage detection and 97.95% for diagnosis recognition with recall values of 94.89% and 99.54%, respectively. The average precision value across all concepts relevant to treatment decisions for patients with known cancer diagnoses (11 concept groups) achieved a precision value of 82.05% with a recall value of 82.45% and an F1-score of 81.81%, respectively. Conclusions The identification of guideline-based information from narrative clinical notes has the potential for implementation as clinical decision support tools.
Published: 2019

17. Re-evaluation of potential predictors of calretinin and mesothelin in a population-based cohort study using assays for the routine application in clinical medicine

Author: Daniel G. Weber, Carmen Töpfer, Georg Johnen, Swaantje Casjens, Dirk Taeger, Irina Raiko, Beate Pesch, Susanne Moebus, Thomas Brüning, Karl-Heinz Jöckel, and Sandra Schonefeld
Subjects: Male, Mesothelioma, medicine.medical_specialty, hypertension, Lung Neoplasms, Population, Medizin, GPI-Linked Proteins, Gastroenterology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, chronic renal failure, Internal medicine, medicine, Biomarkers, Tumor, molecular biology, Humans, Mesothelin, 030212 general & internal medicine, education, Aged, Occupational and Environmental Medicine, education.field_of_study, biology, medicine.diagnostic_test, business.industry, General Medicine, medicine.disease, 030220 oncology & carcinogenesis, Immunoassay, Calbindin 2, Cohort, biology.protein, Medicine, Bronchitis, epidemiology, Calretinin, Clinical Medicine, business, Blood sampling
Abstract: ObjectivesCalretinin and mesothelin are molecular markers for the detection of malignant mesothelioma at early stages. Our objective was the re-evaluation of factors influencing calretinin and mesothelin concentrations in plasma of cancer-free men in order to minimise false-positive tests when using commercial assays approved for clinical diagnostics.SettingThis re-evaluation used data and archived blood samples of the population-based Heinz Nixdorf Recall Study (HNRS) collected from 2011 to 2014.ParticipantsThe present analysis comprised of 569 cancer-free men at the time of blood sampling (median age 70 years) from HNRS.Primary and secondary outcomesMesothelin plasma concentration was determined using ELISA and CLEIA (chemiluminescent enzyme immunoassay). Calretinin plasma concentration was assessed using ELISA.ResultsCompared with the previous determination of concentrations, we detected less false-positive tests using the commercial assays. In this analysis, we found nine false-positive calretinin tests using the ELISA (specificity 98.4%, 95% CI 97.0% to 99.2%) and 24 false-positive mesothelin tests using both ELISA and CLEIA (specificity 95.8%, 95% CI 93.8% to 97.2%). We confirmed renal dysfunction as major predictor of elevated marker concentrations. Mesothelin was additionally affected by bronchitis. Furthermore, elevated inflammation values and hypertension only affected the mesothelin concentration determined by ELISA.ConclusionsThe newly available assays of calretinin and mesothelin approved for clinical diagnostics showed high specificities in the population-based cohort of elderly men without a malignant disease. The current evaluation provides a basis to consider influencing factors in order to further improve the diagnostic procedure.
Published: 2021

18. Prevalence and risk factors of migraine and non-migraine headache in older people : Results of the Heinz Nixdorf Recall study

Author: Susanne Moebus, Zaza Katsarava, Börge Schmidt, Dagny Holle-Lee, Isabell Tenhagen, Sara Schramm, Karl-Heinz Jöckel, and Steffen Naegel
Subjects: Male, Migraine without Aura, medicine.medical_specialty, Aura, Home Environment, Medizinische Fakultät » Universitätsklinikum Essen » Klinik für Neurologie, Population, Migraine with Aura, Medizin, Blood Pressure, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Epidemiology, Prevalence, Medicine, Humans, 030212 general & internal medicine, ddc:610, education, Psychiatry, Child, Medizinische Fakultät » Universitätsklinikum Essen » Institut für Medizinische Informatik, Biometrie und Epidemiologie, Depression (differential diagnoses), Antihypertensive Agents, Aged, education.field_of_study, Epilepsy, Recall, business.industry, Depression, Age Factors, Headache, General Medicine, medicine.disease, Blood pressure, Sleep Quality, Migraine, Hypertension, Female, Neurology (clinical), aura -- blood pressure -- depression -- epidemiology -- Migraine -- older people -- sleep -- sports, business, Older people, Sleep, 030217 neurology & neurosurgery
Abstract: Background The prevalence of migraine and non-migraine headache declines with age. Methods Data from the third visit (2011–2015) of the population-based Heinz Nixdorf Recall study were analysed (n = 2038, 51% women, 65–86 years). Possible risk factors for headache activity (obesity, education, smoking, sports, alcohol, partnership status, living alone, having children, sleep quality, depression, hypertension, diabetes mellitus, stroke, coronary heart disease, medication), and headache symptoms were assessed. We estimated the lifetime prevalence and the prevalence of current active headache of migraine with and without aura, and non-migraine headache. The associations between possible risk factors and headache activity (active vs. inactive) were estimated by age and sex-adjusted odds ratios and 95% confidence intervals (OR [95% CI]) using multiple logistic regression. Results The lifetime prevalence of migraine was 28.6% (n = 584). One hundred and ninety-two (9.4%) had still-active migraine, 168 (3.5%) had migraine with aura, and 416 (5.9%) had migraine without aura. One hundred and sixty-eight (8.2%) had “episodic infrequent migraine, 0–8 headache days/month”, 10 (0.5%) had “episodic frequent migraine, 9–14 headache days/month”, and five (0.2%) had “chronic migraine, ≥15 headache days/month”. Overall, 10 (0.5%) had “chronic headache, any headache on ≥15 days/month”. Female gender and younger age were the most important associated migraine risk factors. Depression (1.62 [1.06; 2.47]) and poor sleep (1.06 [1.00; 1.12]) were associated with migraine and headache activity in general. Antihypertensives were associated with headache remission (0.80 [0.64; 1.00]). Additionally, undertaking less sports (0.72 [0.51; 1.03]) was associated with higher migraine activity. Conclusions Headaches and migraines are not rare in the older population. They are related to mood and sleep disturbance, and migraine even to less physical activity. Antihypertensives are related to headache remission.
Published: 2021

19. Association between socioeconomic position and cystatin C in the Heinz Nixdorf Recall Study

Author: Mirjam Frank, Börge Schmidt, Tanja Zamrik, Raimund Erbel, Carina Emmel, Lars Christian Rump, Nico Dragano, and Karl-Heinz Jöckel
Subjects: Male, medicine.medical_specialty, Epidemiology, Science, Population, Medizin, Blood lipids, Article, Internal medicine, Diabetes mellitus, medicine, Humans, Cystatin C, education, Subclinical infection, Aged, education.field_of_study, Multidisciplinary, biology, business.industry, Middle Aged, medicine.disease, Early Diagnosis, Quartile, Risk factors, Socioeconomic Factors, Cardiovascular Diseases, biology.protein, Medicine, Female, Cystatin, business, Body mass index, Biomarkers
Abstract: Social inequalities in health and disease are well studied. Less information is available on inequalities in biomarker levels indicating subclinical stages of disease such as cystatin C, an early diagnostic marker of renal dysfunction and predictor for cardiovascular disease. We evaluated the relationship between cystatin C, socioeconomic position (SEP) and established cardiovascular risk factors in a population-based study. In 4475 men and women aged 45–75 years participating in the baseline examination of the Heinz Nixdorf Recall Study cystatin C was measured from serum samples with a nephelometric assay. SEP was assessed by education and household income. Linear regression models were used to analyse the association between SEP and cystatin C as well as the impact of cardiovascular risk factors (i.e., body mass index, blood pressure, blood glucose, diabetes mellitus, blood lipids, C-reactive protein, smoking) on this association. After adjustment for age and sex cystatin C decreased by 0.019 mg/l (95% confidence interval (CI) − 0.030 to − 0.008) per five years of education. While using a categorical education variable cystatin C presented 0.039 mg/l (95% CI 0.017–0.061) higher in men and women in the lowest educational category (≤ 10 years of education) compared to the highest category (≥ 18 years). Concerning income, cystatin C decreased by 0.014 mg/l (95% CI − 0.021 to − 0.006) per 1000 € after adjustment for age and sex. For men and women in the lowest income quartile cystatin C was 0.024 mg/l (95% CI 0.009–0.038) higher compared to the highest income quartile. After adjusting for established cardiovascular risk factors the observed associations were substantially diminished. Social inequalities seem to play a role in subclinical stages of renal dysfunction, which are also related to development of cardiovascular disease. Adjustment for traditional cardiovascular risk factors showed that these risk factors largely explain the association between SEP and cystatin C.
Published: 2021

20. Dose-escalated radiotherapy with PET/CT based treatment planning in combination with induction and concurrent chemotherapy in locally advanced (uT3/T4) squamous cell cancer of the esophagus : mature results of a phase I/II trial

Author: Hildegard Lax, Michael Stahl, Ken Herrmann, J. Abu Jawad, Karl-Heinz Jöckel, Nils Lehmann, Thomas Gauler, Christoph Pöttgen, Tanja Trarbach, Martin Stuschke, Stefan Kasper, and Eleni Gkika
Subjects: Male, lcsh:Medical physics. Medical radiology. Nuclear medicine, medicine.medical_specialty, Esophageal Neoplasms, medicine.medical_treatment, lcsh:R895-920, Esophageal cancer, Urology, Medizin, Neutropenia, lcsh:RC254-282, 03 medical and health sciences, Folinic acid, 0302 clinical medicine, Positron Emission Tomography Computed Tomography, Squamous cell carcinoma, Dose-escalation, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Radiology, Nuclear Medicine and imaging, Progression-free survival, Prospective Studies, Radiation treatment planning, 030304 developmental biology, Aged, 0303 health sciences, business.industry, Research, Radiotherapy Planning, Computer-Assisted, Induction chemotherapy, Radiotherapy Dosage, Chemoradiotherapy, Induction Chemotherapy, Middle Aged, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Definitive chemoradiation, Irinotecan, Radiation therapy, Oncology, 030220 oncology & carcinogenesis, Female, Esophageal Squamous Cell Carcinoma, business, medicine.drug
Abstract: Background This prospective phase I/II trial assessed feasibility and efficacy of dose-escalated definitive chemoradiation after induction chemotherapy in locally advanced esophageal cancer. Primary study endpoint was loco-regional progression-free survival at 1 year. Methods Eligible patients received 2 cycles of induction chemotherapy with irinotecan, folinic acid and 5-fluorouracil weekly and cisplatin every 2 weeks (weeks 1–6, 8–13) followed by concurrent chemoradiation with cisplatin and irinotecan (weeks 14, 15, 17, 18, 20). Radiotherapy dose escalation was performed in three steps (60 Gy, 66 Gy, 72 Gy) using conventional fractionation, planning target volumes were delineated with the aid of 18F-FDG-PET/CT scans. During follow-up, endoscopic examinations were performed at regular intervals. Results Between 09/2006 and 02/2010, 17 patients were enrolled (male/female:13/4, median age: 59 [range 48–66] years, stage uT3N0/T3N1/T4N1: 4/12/1). One patient progressed during induction chemotherapy and underwent surgery. Of 16 patients treated with definitive chemoradiotherapy, 9 (56%) achieved complete response after completion of chemoradiation. One-, 2-, 3- and 5-year overall survival rates (OS) were 77% [95%CI: 59–100], 53% [34–83], 41% [23–73], and 29% [14–61], respectively. Loco-regional progression-free survival at 1, 3, and 5 years was 59% [40–88], 35% [19–67], and 29% [14–61], corresponding cumulative incidences of loco-regional progressions were 18% [4–39%], 35% [14–58%], and 41% [17–64%]. No treatment related deaths occurred. Grade 3 toxicities during induction therapy were: neutropenia (41%), diarrhoea (41%), during combined treatment: neutropenia (62%) and thrombocytopenia (25%). Conclusions Dose-escalated radiotherapy and concurrent cisplatin/irinotecan after cisplatin/irinotecan/5FU induction chemotherapy was tolerable. The hypothesized phase II one-year loco-regional progression free survival rate of 74% was not achieved. Long-term survival compares well with other studies on definitive radiotherapy using irinotecan and cisplatin but is not better than recent trials using conventionally fractionated radiotherapy ad 50 Gy with concurrent paclitaxel or 5FU and platinum compound. Trial registration The present trial was registered as a phase I/II trial at the EudraCT database: Nr. 2005-006097-10 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-006097-10/DE) and authorized to proceed on 2006-09-25.
Published: 2021

21. Associations between haemoglobin A(1c)and mortality rate in the KORA S4 and the Heinz Nixdorf Recall population-based cohort studies

Author: Oliver Kuß, Barbara Thorand, Michael Roden, Bernd Kowall, Christa Meisinger, Annette Peters, Karl-Heinz Jöckel, Cornelia Huth, Andreas Stang, Christian Herder, Raimund Erbel, and Wolfgang Rathmann
Subjects: medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Mortality rate, Epidemiology, Hba(1c), Mortality, Pre-diabetes, Type-2 Diabetes, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, medicine.disease, Confidence interval, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Diabetes mellitus, Relative risk, Internal Medicine, medicine, Prediabetes, ddc:610, business, Demography, Cohort study
Abstract: Background There is limited knowledge about mortality risk in persons with increased haemoglobin A(1c)(HbA(1c)) levels below the diabetes threshold. Moreover, little is known about how associations between increased HbA(1c)and mortality depend on the length of follow-up. Therefore, we studied associations between HbA(1c)and mortality over long-term follow-up in persons with and without known diabetes. Methods We used data from two German population-based cohort studies: KORA S4 Study (Southern Germany, n = 1458, baseline visits in 1999 to 2001, baseline age 55 to 74 years, mortality follow-up 16.8 years) and Heinz Nixdorf Recall (HNR) Study (Ruhr area, n = 4613, baseline visits in 2000 to 2003, baseline age 45 to 75 years, mortality follow-up 17.8 years). Adjusted log-linear models were fitted to estimate relative risks (RRs) with 95% confidence intervals (CI). Results In both cohorts, participants with HbA(1c)39 to 41 mmol/mol (5.7%-5.9%) and HbA(1c)42 to 46 mmol/mol (6.0% to 6.4%) did not have a larger overall mortality risk than participants with HbA(1c) < 39 mmol/mol (5.7%): the corresponding adjusted RRs were 1.00 (95% CI: 0.83-1.21) and 1.01 (0.80-1.27) in KORA and 0.99 (0.82-1.21) and 0.83 (0.65-1.07) in the HNR Study. For the pooled cohorts, the RR for HbA(1c)39 to 46 mmol/mol (5.7%-6.4%) was 0.96 (0.85-1.07). Associations between newly detected diabetes (HbA(1c) >= 6.5%) and mortality were weak after 4 and 8 years of follow-up, but were stronger after 12 years of follow-up, whereas associations between previously known diabetes (baseline) and mortality decreased. Conclusions HbA(1c)-defined pre-diabetes is not associated with overall mortality. For newly detected and previously known diabetes, mortality risks vary with length of follow-up.
Published: 2021

22. Interim PET Evaluation in Diffuse Large B-Cell Lymphoma Using Published Recommendations : Comparison of the Deauville 5-Point Scale and the ΔSUVmₐₓ Method

Author: Fonyuy Nyuyki, Daniëlle M. E. van Assema, Thomas Krohn, Matthias Weckesser, Lilli Geworski, A. Hertel, Jan Rekowski, Christine Schmitz, Lars Kurch, Frank M. Bengel, Christiane Franzius, Ingo Brink, Jens Holzinger, Karl-Heinz Jöckel, Ulrich Dührsen, Dirk Hasenclever, Andreas Hüttmann, Jörg Kotzerke, Martin Freesmeyer, Uwe Haberkorn, Stefan P. Müller, and VU University medical center
Subjects: Oncology, medicine.medical_specialty, business.industry, Proportional hazards model, Concordance, Hazard ratio, Medizin, medicine.disease, Interim pet, Spearman's rank correlation coefficient, Confidence interval, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Medicine, Cutoff, Radiology, Nuclear Medicine and imaging, business, Diffuse large B-cell lymphoma, 030215 immunology
Abstract: The value of interim 18F-FDG PET/CT (iPET)-guided treatment decisions in patients with diffuse large B-cell lymphoma (DLBCL) has been the subject of much debate. This investigation focuses on a comparison of the Deauville score and the change-in-SUV max (DSUV max) approach-2 methods to assess early metabolic response to standard chemotherapy in DLBCL. Methods: Of 609 DLBCL patients participating in the PET-Guided Therapy of Aggressive Non-Hodgkin Lymphomas trial, iPET scans of 596 patients originally evaluated using the DSUV max method were available for post hoc assessment of the Deauville score. A commonly used definition of an unfavorable iPET result according to the Deauville score is an uptake greater than that of the liver, whereas an unfavorable iPET scan with regard to the ΔSUV max approach is characterized as a relative reduction of the SUV max between baseline and iPET staging of less than or equal to 66%. We investigated the 2 methods' correlation and concordance by Spearman rank correlation coefficient and the agreement in classification, respectively. We further used Kaplan-Meier curves and Cox regression to assess differences in survival between patient subgroups defined by the prespecified cutoffs. Time-dependent receiver-operating-characteristic curve analysis provided information on the methods' respective discrimination performance. Results: Deauville score and DSUV max approach differed in their iPET-based prognosis. The ΔSUV max approach outperformed the Deauville score in terms of discrimination performance-most likely because of a high number of false-positive decisions by the Deauville score. Cutoff-independent discrimination performance remained low for both methods, but cutoff-related analyses showed promising results. Both favored the ΔSUV max approach, for example, for the segregation by iPET response, where the event-free survival hazard ratio was 3.14 (95% confidence interval, 2.22-4.46) for ΔSUV max and 1.70 (95% confidence interval, 1.29-2.24) for the Deauville score. Conclusion: When considering treatment intensification, the currently used Deauville score cutoff of an uptake above that of the liver seems to be inappropriate and associated with potential harm for DLBCL patients. The ΔSUV max criterion of a relative reduction in SUV max of less than or equal to 66% should be considered as an alternative.
Published: 2021

23. Application of two job indices for general occupational demands in a pooled analysis of case–control studies on lung cancer

Author: Neil E. Caporaso, Ann Olsson, Dana Mates, Cristina Fortes, Tamás Pándics, Simonato Lorenzo, Jolanta Lissowska, Kurt Straif, Beate Pesch, Jan Hovanec, Guillermo Fernández-Tardón, Hans Kromhout, Pascal Guénel, Karl-Heinz Jöckel, Eleonora Fabianova, Roel Vermeulen, Wolfgang Ahrens, Stefan Karrasch, Hermann Pohlabeln, John K. Field, Joachim Schüz, Vladimir Bencko, Beata Świątkowska, Thomas Brüning, Dario Consonni, Danièle Luce, Thomas Behrens, Maria Teresa Landi, David I. Conway, John R. McLaughlin, Per Gustavsson, Paolo Boffetta, Marie-Élise Parent, Vladimir Janout, Franco Merletti, Lorenzo Richiardi, Lenka Foretova, Heinz-Erich Wichmann, David Zaridze, Swaantje Casjens, Paul A. Demers, Jack Siemiatycki, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Ruhr-Universität Bochum [Bochum], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), University of Glasgow, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Ruhrlandklinik University Hospital, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, Universität Bremen, Helmholtz Zentrum München = German Research Center for Environmental Health, Ludwig-Maximilians-Universität München (LMU), Karolinska Institute, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli studi di Torino = University of Turin (UNITO), Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Toronto, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Universidad de Oviedo [Oviedo], CIBER de Epidemiología y Salud Pública (CIBERESP), N.N. Blokhin National Medical Research Center of Oncology, Nofer Institute of Occupational Medicine (NIOM), National Public Health Centre, Medical University of Warsaw - Poland, University of Liverpool, National Institute of Public Health [Romania] (INSP), Charles University [Prague] (CU), Masaryk Memorial Cancer Institute (MMCI), Palacky University Olomouc, Universiteit Utrecht, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Stony Brook University [SUNY] (SBU), State University of New York (SUNY), German Social Accident Insurance [FP 271], Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Helmholtz-Zentrum München (HZM), University of Turin, University Hospital of Padua, Masaryk Memorial Cancer Institute (RECAMO), Chard-Hutchinson, Xavier, Hovanec J., Siemiatycki J., Conway D.I., Olsson A., Guenel P., Luce D., Jockel K.-H., Pohlabeln H., Ahrens W., Karrasch S., Wichmann H.-E., Gustavsson P., Consonni D., Merletti F., Richiardi L., Simonato L., Fortes C., Parent M.-E., McLaughlin J.R., Demers P., Landi M.T., Caporaso N., Fernandez-Tardon G., Zaridze D., Swiatkowska B., Pandics T., Lissowska J., Fabianova E., Field J.K., Mates D., Bencko V., Foretova L., Janout V., Kromhout H., Vermeulen R., Boffetta P., Straif K., Schuz J., Casjens S., Pesch B., Bruning T., and Behrens T.
Subjects: Male, Lung Neoplasms, Occupational prestige, Short Communication, [SDV]Life Sciences [q-bio], Medizin, Logistic regression, 03 medical and health sciences, occupational demand, 0302 clinical medicine, Occupational Exposure, medicine, Odds Ratio, case–control, Humans, cancer, Risk factor, Occupations, Lung cancer, job index, business.industry, Environmental and Occupational Health, Smoking, Public Health, Environmental and Occupational Health, Cancer, Odds ratio, Social prestige, medicine.disease, 030210 environmental & occupational health, Confidence interval, Key terms job index, [SDV] Life Sciences [q-bio], lung cancer, Tumor subtype, Case-Control Studies, Female, Public Health, Public aspects of medicine, RA1-1270, business, Psychosocial, Tumor Subtype, Job index, Social Prestige, Demography
Abstract: The German Social Accident Insurance supported this study (grant number FP 271)., Hovanec J, Siemiatycki J, Conway DI, Olsson A, Guenel P, Luce D, Jöckel KH, Pohlabeln H, Ahrens W, Karrasch S, Wichmann HE, Gustavsson P, Consonni D, Merletti F, Richiardi L, Lorenzo S, Fortes C, Parent MÉ, McLaughlin JR, Demers P, Landi MT, Caporaso N, Fernández-Tardón G, Zaridze D, Świątkowska B, Pándics T, Lissowska J, Fabianova E, Field JK, Mates D, Bencko V, Foretova L, Janout V, Kromhout H, Vermeulen R, Boffetta P, Straif K, Schüz J, Casjens S, Pesch B, Brüning T, Behrens T.
Published: 2021

24. Long-term low-level ambient air pollution exposure and risk of lung cancer – A pooled analysis of 7 European cohorts

Author: Klea Katsouyanni, Jochem O. Klompmaker, Per E. Schwarze, Göran Pershagen, Massimo Stafoggia, Alois Lang, Carla H. van Gils, Richard Atkinson, Sophia Rodopoulou, Giulia Cesaroni, Danielle Vienneau, Kathrin Wolf, Ulla Arthur Hvidtfeldt, Torben Sigsgaard, Gabriele Nagel, Bert Brunekreef, Francesco Forastiere, Amar Mehta, Mette Kildevæld Simonsen, Annette Peters, Gudrun Weinmayr, Mariska Bauwelinck, Tom Bellander, Matthias Ketzel, Jørgen Brandt, Norun Hjertager Krog, Evangelia Samoli, John S. Gulliver, Matteo Renzi, Karl-Heinz Jöckel, Ole Hertel, Jeanette Therming Jørgensen, Hans Concin, Petter Ljungman, Daniela Fecht, Nicole Janssen, Kees de Hoogh, Gianluca Severi, Karin Leander, Ole Raaschou-Nielsen, Barbara Hoffmann, Debora Rizzuto, Zorana Jovanovic Andersen, Patrik K. E. Magnusson, Maciek Strak, Shuo Liu, Jie Chen, Gerard Hoek, Marie-Christine Boutron-Ruault, Raphael Simon Peter, Bente Oftedal, Interface Demography, Faculty of Economic and Social Sciences and Solvay Business School, and Sociology
Subjects: Lung Neoplasms, 010504 meteorology & atmospheric sciences, Air pollution, Medizin, 010501 environmental sciences, medicine.disease_cause, 01 natural sciences, Environmental Science(all), Environmental health, Medicine, Humans, Lung cancer, Air quality index, lcsh:Environmental sciences, 0105 earth and related environmental sciences, General Environmental Science, lcsh:GE1-350, Air Pollutants, business.industry, Proportional hazards model, Incidence (epidemiology), Air Pollution, Dose Response Relationship, Lung Cancer Incidence, Particulate Matter, Environmental exposure, Environmental Exposure, medicine.disease, Europe, Dose response relationship, Cohort, Lung cancer incidence, business, Particulate matter, Body mass index, Environmental Sciences
Abstract: Background/aim: Ambient air pollution has been associated with lung cancer, but the shape of the exposure-response function - especially at low exposure levels - is not well described. The aim of this study was to address the relationship between long-term low-level air pollution exposure and lung cancer incidence. Methods: The “Effects of Low-level Air Pollution: a Study in Europe” (ELAPSE) collaboration pools seven cohorts from across Europe. We developed hybrid models combining air pollution monitoring, land use data, satellite observations, and dispersion model estimates for nitrogen dioxide (NO2), fine particulate matter (PM2.5), black carbon (BC), and ozone (O3) to assign exposure to cohort participants’ residential addresses in 100 m by 100 m grids. We applied stratified Cox proportional hazards models, adjusting for potential confounders (age, sex, calendar year, marital status, smoking, body mass index, employment status, and neighborhood-level socio-economic status). We fitted linear models, linear models in subsets, Shape-Constrained Health Impact Functions (SCHIF), and natural cubic spline models to assess the shape of the association between air pollution and lung cancer at concentrations below existing standards and guidelines. Results: The analyses included 307,550 cohort participants. During a mean follow-up of 18.1 years, 3956 incident lung cancer cases occurred. Median (Q1, Q3) annual (2010) exposure levels of NO2, PM2.5, BC and O3 (warm season) were 24.2 µg/m3 (19.5, 29.7), 15.4 µg/m3 (12.8, 17.3), 1.6 10−5m−1 (1.3, 1.8), and 86.6 µg/m3 (78.5, 92.9), respectively. We observed a higher risk for lung cancer with higher exposure to PM2.5 (HR: 1.13, 95% CI: 1.05, 1.23 per 5 µg/m3). This association was robust to adjustment for other pollutants. The SCHIF, spline and subset analyses suggested a linear or supra-linear association with no evidence of a threshold. In subset analyses, risk estimates were clearly elevated for the subset of subjects with exposure below the EU limit value of 25 µg/m3. We did not observe associations between NO2, BC or O3 and lung cancer incidence. Conclusions: Long-term ambient PM2.5 exposure is associated with lung cancer incidence even at concentrations below current EU limit values and possibly WHO Air Quality Guidelines.
Published: 2021

25. Author response: Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author: Zahra Mohammadi, Abdul Basit, Helena I. S. Nogueira, Soile E. Puhakka, Hongsheng Bi, Ari Voutilainen, Davood Khalili, Bin Zhou, Dermot O'Reilly, Natascia Rinaldo, Paulo A. Lotufo, Bahareh Kheiri, Thein Thein Htay, Simona Giampaoli, Goodarz Danaei, M. Fernanda Lima-Costa, Simona Bo, Peter Schnohr, Jerzy Chudek, Francesco Panza, Ling Yang, Katia Vergetti Bloch, Vincenzo Capuano, Holly E. Syddall, Dong Zhao, Indah Suci Widyahening, Maria Lorenza Muiesan, Leng Huat Foo, Mohsen Azimi-Nezhad, Merete Osler, Laura Torres-Collado, Manu Raj, Adroaldo Cesar Araujo Gaya, Susi Kriemler, Ali Akbar Shayesteh, Aneta Grajda, Anette Varbo, Kazem Mohammad, Leila Beltrami Moreira, Shu Ti Chiou, Iuliia A Rusakova, Jyh Eiin Wong, Torben Jørgensen, Lela Sturua, Lubica Ticha, Hamid Hakimi, Hazzaa M. Al-Hazzaa, Yanina Zócalo, Freda Pitakaka, Savvas C. Savva, Rajeev Gupta, Jennifer Servais, Marie Kunešová, Johanna M. Geleijnse, Elysée Claude Bika Lele, Yannis Manios, Jorge Escobedo-de la Peña, Yufang Bi, Chinh Nguyen Huu, Sibel Gogen, Viviane Cunha Cardoso, Kristine H. Allin, Ana Azevedo, Line Tang Møllehave, Vincent Jr DeGennaro, Novie O. Younger-Coleman, Gretchen A Stevens, Dickman Gareta, Holger Theobald, Anja Schienkiewitz, Bekbolat Zholdin, Janice Luisa Lukrafka, Adela Chirita-Emandi, Ulla Roggenbuck, Kenisha Russell Jonsson, Robespierre Ribeiro, Gabriele Eiben, Eero Kajantie, Sounnia Mediene Benchekor, Fariborz Mansour-Ghanaei, Mary Simon, Prakash C. Gupta, Mohammad Esmaeel Motlagh, Emanuela Gualdi-Russo, María Elena Díaz-Sánchez, Pilar Guallar-Castillón, Bee Koon Poh, Cristina Padez, Azaliia M Tuliakova, Sarah P. Garnett, William R. Tebar, Yingfeng Zheng, Suhad Bahijri, Christina Mavrogianni, Mihaela Vladulescu, Jan A. Staessen, Paula Duarte de Oliveira, Rui Ornelas, Michael Sjöström, Charles Agyemang, Slawomir Koziel, Shohreh Naderimagham, Jari Jokelainen, Stephen T. McGarvey, Patrick Pasquet, Farnam Mohebi, Nader Saki, Aida Pilav, Azim Nejatizadeh, Marianna Noale, Habiba Ben Romdhane, Luís B. Sardinha, Laura Lauria, Jun Hata, Kodanda R Kanala, Gert B. M. Mensink, Nils Lehmann, Elio Riboli, Carolina Tarqui-Mamani, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Luis Serra-Majem, Martina Müller-Nurasyid, Felipe Vogt Cureau, Lekhraj Rampal, Zhamilya Battakova, Ludmila Sevcikova, Suhaila Abdul Ghaffar, Fikru Tullu, Aung Soe Htet, Angel R. Gonzalez, Annette J. Dobson, Kavumpurathu Raman Thankappan, Hélène Delisle, Francisco J. Félix-Redondo, Ramón Suárez-Medina, Annika Rosengren, Sania Nishtar, Tanja G. M. Vrijkotte, Wolfgang Ahrens, Osvaldo Santos, Maria Cecília Formoso Assunção, Kazi M. Jamil, Stefano Marventano, Wenbin Wei, Norsyamlina Che Abdul Rahim, Shukri F. Mohamed, Bente Sparboe-Nilsen, Soon-Woo Park, Ana Isabel Rito, David Goltzman, W. M. Monique Verschuren, Catterina Ferreccio, Marta Buoncristiano, Ramón Alberto Rascón-Pacheco, Pradeep Joshi, Edward D Janus, Laetitia Huiart, Ala'a Alkerwi, Lorenza Pilotto, Mohannad Al Nsour, Daan Kromhout, Marius B. Bjertness, Oanh T. H. Trinh, Nico Dragano, Angélica Ochoa-Avilés, Ingunn Holden Bergh, Yuki Fujita, Juraci Almeida Cesar, Hajer Aounallah-Skhiri, Maria Dorobantu, Jordi Sunyer, Wolfgang Kratzer, Susanne R. de Rooij, Drude Molbo, Rebecca Goldsmith, Jean Woo, Mohammad El-khateeb, Tiffany K. Gill, Nish Chaturvedi, Benjamin Acosta-Cazares, Erik Lykke Mortensen, Nikhil D. Patel, Francesco Pistelli, Yuan He, Ivana Radic, Yi Zeng, Ilse Khouw, Reynaldo Martorell, Ching-Yu Cheng, Stine Schramm, Hana Shimizu-Furusawa, Jacek Jóźwiak, Radwan Qasrawi, Isti Ilmiati Fujiati, Charles Sossa Jérome, Ben Schöttker, Mikhail Benet, Anastasia Markaki, Christopher T. Cowell, Bharathi Viswanathan, Renata Kuciene, Jose Eugenio Lozano, Pedro J Ortiz, Delphine De Smedt, Elaine M. Murtagh, Kamel Ajlouni, Carlos A. Aguilar-Salinas, Graziella D'Arrigo, Xiangjun Wang, Lars Lind, Macia Enguerran, Marjeta Mišigoj-Duraković, Bo Werner, Jean-Michel Gaspoz, Kyungwon Oh, Seyed Rasoul Zakavi, Daniel Fernández-Bergés, Felix Kaducu, Ramon O. Jimenez, Jonathan E. Shaw, Nipa Rojroongwasinkul, Aicha Soumare, Astrid Petersmann, Tomasz Grodzicki, Parvina Mukhtorova, Eha Nurk, Bhawesh Koirala, Óscar Lopes, Ana Jelakovic, Karolina Milkowska, Magda Gasull, Regina Heidinger-Felso, Marcela González-Gross, Belong Cho, Daphne Mirkopoulou, Salvador Villalpando, Tran Quoc Bao, José Boggia, Daniela Galeone, Josep Redon, Matthias Bopp, Abbas Rezaianzadeh, Dusko Bjelica, Amir Houshang Mehrparvar, Felipe F. Casanueva, Khairil Si-Ramlee, Soheir H Ahmed, Maria Nordendahl, Luciana Zaccagni, Mahboubeh Parsaeian, Rod Jackson, Jorge Motta, Keiu Nelis, Fernando Rigo, Andrzej Pajak, Christa Meisinger, Clara Homs, Namuna Shrestha, Mar Alvarez-Pedrerol, Xun Tang, Johann Willeit, Motahareh Kheradmand, Jean Dallongeville, Jean-Bernard Ruidavets, Anne Tjønneland, Diana A. Santos, Lynne M. Boddy, Jie Hao, David Alejandro González-Chica, Elin Kolle, Jingli Gao, Małgorzata Mossakowska, Isabel O. Oliveira, Giuseppe Grosso, Seongjun Ha, Olfa Saidi, Albina A Fakhretdinova, Oye Gureje, Raluca Pop, Iulia Jurca Simina, Nuno Lunet, Maria Forsner, Peter Bjerregaard, Rachael McLean, Antonio Cabrera de León, Guy De Backer, José A. Casajús, Guang Ning, Emmanuella Magriplis, Laura Censi, Graziella Bruno, Valentina Peterkova, Angelique Chan, Yvonne T. van der Schouw, Charalambos Hadjigeorgiou, Anjani Kumar Jha, Toomas Veidebaum, Thamara Hubler Figueiró, Jana Kratenova, Michelle Cilia, Ivo Rakovac, Bill Stavreski, Ya Xing Wang, Oscar Noboa, Romana Roccaldo, Sara Magnacca, Johan Sundström, Peter Stehle, Tania Lopez, Francis Delpeuch, Julianne Williams, Ellisiv B. Mathiesen, Leanne M. Riley, Claudia M. Hormiga, Joanne Katz, Ekaterina Stoyanova, Heloisa Bettiol, Gabriele Nagel, Alireza Khosravi, Lars Bo Andersen, João Breda, Jørgen Meisfjord, Ahmad Faudzi Yusoff, Marjeta Majer, Robert Beaglehole, Caleb Ochimana, Shynar Abdrakhmanova, George S. Stergiou, Blanca Sandra Ruiz-Betancourt, Leon A. Simons, Eng Joo Tan, Victoria Farrugia Sant'Angelo, Gry Skodje, Maryam Keramati, Liv Elin Torheim, Seppo Koskinen, Assembekov Batyrbek, Jaakko Tuomilehto, Marjo-Riitta Järvelin, Ming-Hui Zhao, Krista Fischer, Tobias F. Rinke de Wit, Agnès Le Port, Reza Homayounfar, James E. Bennett, Yuna He, Matsuda Fumihiko, Qi Sheng You, Angela Spinelli, Scott B. McLean, Shirin Djalalinia, Thet Thet Mu, Yves Martin-Prével, Rafael N. Pichardo, Gailute Bernotiene, Pietro Amedeo Modesti, Frederick C. W. Wu, Chandini Nekkantti, Daniela Rodrigues, Tandi E. Matsha, Mihai Gafencu, Xingwang Ye, Salar Rahimikazerooni, Trevor S. Ferguson, Christophe Tzourio, Marie Zins, Fernando Rodríguez-Artalejo, Xu Ma, Elin Pettersen Sørgjerd, Lourdes Ribas-Barba, Nalan Uysal, Salim Berkinbayev, Enisa Kujundzic, Sari Voutilainen, Iraj Mohebbi, Heiner Boeing, Jorge Mota, Jana Námešná, Maria Tsigga, Zivka Dika, Gulmira Aitmurzaeva, Xu Lin, Valéria Regecová, Herman Schargrodsky, Stevo Popovic, Amelia C. Crampin, Hannu Uusitalo, André Luiz Sena Guimarães, Ali Esmaeili, Catherine Kyobutungi, Virginija Dulskiene, Diego Augusto Santos Silva, David De Ridder, Lizzy M. Brewster, Hashem Jaddou, Eunice Ugel, José Camolas, Azli Baharudin, Idris Guessous, Sok King Ong, Tabara Yasuharu, Ali Ghanbari, Anne W. Taylor, Iraj Nabipour, Justyna Godos, Cyrus Cooper, Bruna Gonçalves Cordeiro da Silva, Gonzalo Valdivia, Gyulli M. Kazakbaeva, Takuro Furusawa, Pawel Kurjata, Diego Vanuzzo, Marvin Cervantes-Loaiza, Karen Morgan, Mostafa Qorbani, Rute Santos, Marika Ferrari, Diego Salmerón, Ida Maria Schmidt, Gao Pei, Abu Am Hanif, Balkish M. Naidu, Maria Wany Louzada Strufaldi, Moesijanti Soekatri, Marcia Scazufca, Katharina Maruszczak, Jacqueline Ramke, Elvis Oa Wambiya, Kairit Mikkel, Napoleón Pérez-Farinós, Natalia Nowak-Szczepanska, Miao Li Chee, Jose Sanchez-Abanto, Rajaa Al-Raddadi, Michel Joffres, Vayia Rarra, Ningli Wang, Charmaine A. Duante, Sheikh Mohammed Shariful Islam, Manoli Garcia-de-la-Hera, Weili Yan, Dong Wook Shin, Rômulo Araújo Fernandes, Ilona Nenko, Sanjib Kumar Sharma, Alfonso Siani, Indrapal I. Meshram, Imelda A. Agdeppa, Ei Ei K. Nang, Ian Rouse, Avula Laxmaiah, Ana M. B. Menezes, Yih Chung Tham, Ebrahim Eftekhar, María José Tormo, Felicia Cañete, Marie Eliasen, Lutgart Braeckman, Dirk Vanderschueren, Genc Burazeri, Kari Kuulasmaa, Jesús Vioque, Marisa K. Sophiea, Agneta Sjöberg, Katarzyna Dereń, Albertino Damasceno, Jochanan Stessman, Stig E. Bojesen, Aline Meirhaeghe, Else Karin Grøholt, Flávio Danni Fuchs, Robert Lundqvist, Frédéric Gottrand, Jeongseon Kim, Helmut Schröder, Joanna Baran, Karina Mary de Paiva, Yousef Khader, Eric Monterrubio-Flores, Aneta Weres, Hans Concin, Damaskini Valvi, Sari Hantunen, Machi Suka, Elena Sacchini, Norbert Amougou, Ursula Kiechl-Kohlendorfer, Edwige Landais, Viktoria Anna Kovacs, Rosemarie Martin, Kenneth James, Amaneh Shayanrad, Grethe S. Tell, Norazizah Ibrahim Wong, Vedrana Sember, Anelise Reis Gaya, Konrad Jamrozik, Thorkild I. A. Sørensen, Martin Neovius, Urho M. Kujala, Nathalie Michels, Marcel Goldberg, Alexandra Cucu, Liliana Dacica, Adelheid Weber, Hermann Pohlabeln, Sandjaja, Jukka T. Salonen, Patricia Varona-Pérez, Tiina Laatikainen, Jolanta Słowikowska-Hilczer, Ana Paula Carlos Cândido, Julie Taylor, Anabela Mota-Pinto, Cora L. Craig, Teresa Shamah-Levy, María Dolores Chirlaque, Mohd Azahadi Omar, Dominique Cottel, Charumathi Sabanayagam, Andrea Gazzinelli, Mieczysław Litwin, Sadaf G. Sepanlou, Adolfo Rubinstein, Abbas Dehghan, Rildo de Souza Wanderley Júnior, Wenhua Zhao, Aleksandra Piwońska, Yong Tao, Bontha V. Babu, Marc J. Gunter, Harunobu Nakamura, Wojciech Drygas, Eiji Oda, Jia Li Duan, Stefan Söderberg, Anthony Kafatos, Lynell V Maniego, Els Clays, Wei-Yen Lim, Marshall K. Tulloch-Reid, Mariachiara Di Cesare, Mattias Johansson, Simona Costanzo, Margot González-León, Matthias Nauck, Henry Völzke, George Luiz Lins Machado-Coelho, Annette Peters, Rajiv T Erasmus, Juan Francisco Miquel, Andrea Gualtieri, Abdul Hamid Zargar, Kaare Christensen, Peter Willeit, Tanja Stocks, Christine Cameron, Samuel C. Dumith, Janina Petkeviciene, Boyd Swinburn, Magdalena Muc, Sabine Schipf, Tajana Zeljkovic Vrkic, Martin Bobak, Damian K Francis, Veronica Mocanu, Karien Stronks, Antonisamy Belavendra, Artur Mazur, Nagalla Balakrishna, Jardena J. Puder, Mehrdad Azmin, Shelly R. McFarlane, Sara Santos Sanz, Yang Yang, Anneke Blokstra, Rafel Ramos, Ertugrul Celikcan, Jody C Miller, Jesús Ibarluzea, Svetlana A. Shalnova, Maria Elisa Zapata, Guansheng Ma, Fereidoun Azizi, Beatriz D'Agord Schaan, Pedro Marques-Vidal, William A. Neal, Ana B. Crujeiras, Zhenyu Zhang, Naser Ahmadi, Abdullatif Husseini, Alun Evans, Jiang He, Edyta Łuszczki, Maria G. Stathopoulou, Alibek Mereke, Mari-Liis Tammesoo, Axel C. Carlsson, Helen Gonçalves, Idowu O Senbanjo, Jim Mann, Rajendra Pradeepa, Juel Jarani, Eva Martos, Eugene Sobngwi, Themistoklis Tzotzas, Vassilis Zafiropulos, Reina Engle-Stone, Atul Trivedi, Hui Cai, Sarah Filippi, Georg Posch, Galina Obreja, Cecily Kelleher, Sareh Eghtesad, Chung T Nguyen, Kay-Tee Khaw, Joseph Cacciottolo, Ana Henriques, Yi-Ting Lin, Anil Poudyal, Liam Smeeth, Kenji Shibuya, Emma Ruiz Moreno, Annamari Lundqvist, Thor Aspelund, Caroline H.D. Fall, Philippe Amouyel, Kristyna Zejglicova, Argyro Karakosta, Piotr Bandosz, Juvenal Soares Dias-da-Costa, Maria Lazo-Porras, Maung Maung Than Htike, Dalia Luksiene, Jutta Stieber, Augusto Di Castelnuovo, Aryeh D. Stein, Lechaba Tshepo, Judith Benedics, Aletta E. Schutte, Jürgen König, Magdalena Korzycka, Grzegorz Sobek, Dimitrios Trichopoulos, Tai Hing Lam, Yn-Tz Sung, Masanori Iwasaki, Elias F. Gudmundsson, Antonio Mistretta, Daniel Lemogoum, Nimmathota Arlappa, Isabelle Herter-Aeberli, Khanh Le Nguyen Bao, Shoichiro Tsugane, Kaosar Afsana, Alireza Sadjadi, Myriam Galfo, Jean Claude Mbanya, Bernardo L. Horta, Marleen E. Hendriks, M. Arfan Ikram, Fadia AlBuhairan, Huashuai Chen, Marzieh Katibeh, Sidsel Graff-Iversen, Sahar Saeedi Moghaddam, Larissa Pruner Marques, Louise Eriksen, Aleksandra Gomula, Ricky Eddie, Maciej Banach, Jost B. Jonas, Andrea R. V. R. Horimoto, Slavica Sović, Charles Mondo, Felix Gutzwiller, Mariana Sbaraini, Aye Aye Sein, Henrike Galenkamp, Jaume Marrugat, Nazan Yardim, Cecilia Björkelund, Luigi Palmieri, Roya Kelishadi, Jie Mi, Nahla Hwalla, Jing Liu, Davide Noto, Panayiotis K. Yiallouros, Kelias P. Msyamboza, Judith Simons, Sofia Malyutina, Michele Monroy-Valle, Andres Metspalu, Lariane M Ono, Rafaela Rosário, Flora A. Ukoli, Efthymios Kapantais, Enzo Manzato, S. Goya Wannamethee, Alison J Price, Gregorio Varela-Moreiras, Ali Reza Safarpour, Erfan Ghasemi, Janine Clarke, René Charles Sylva, Wan Nazaimoon Wan Mohamud, Zhamyila Usupova, Chaoqiang Jiang, Julio Zuñiga Cisneros, Freja B Kampmann, Wei Cheng Lo, Reza Mohammadpourhodki, Kaspar Staub, Mojtaba Farjam, Vincenzo Solfrizzi, Garry L. Jennings, Fabio Galvano, Monika Zuziak, Karin De Ridder, Lucie Viet, Anna Bugge, Mehdi Yaseri, Safiah Md Yusof, Sandra C. Fuchs, Emmanuel Cohen, Snehalatha Chamukuttan, Maria Ruiz-Castell, Karen Sparrenberger, Pedro Plans-Rubio, Wei Zheng, Eldridge Ferrer, Martijn Huisman, Maria Hassapidou, Iris Pigeot, Jakub Stokwiszewski, Domenico Palli, Ewelina Czenczek-Lewandowska, Ramiro Guerrero, Farzad Hadaegh, Han Cg Kemper, Saeid Safiri, Ivan Pećin, Arnaud Chiolero, Niels Møller, Jorge Bezerra, Ulrike Gehring, Iná S. Santos, Dénes Molnár, Muhammad Fadhli Mohd Yusoff, Marie Moitry, Nizal Sarrafzadegan, Jacqueline F. Price, Ranko Stevanovic, Sai Yin Ho, Georg Lappas, Alberto Palloni, Malay K. Mridha, Elaine M. Dennison, Jeonghee Lee, Saeid Eslami, Rahman Shiri, Japhet Killewo, Juergen Breckenkamp, Mathilde Kersting, Y Nikitin, Iqbal Bata, Geetha R Menon, Maria Avdicova, Sanjay Rampal, Antônio Augusto Moura da Silva, Kirsten Mehlig, Chien-An Sun, Ramin Heshmat, Violeta Iotova, Stefaan Demarest, Mette Rasmussen, Dirk De Bacquer, San-Lin You, Suzanne N Morin, Martin Gulliford, Maties Torrent, Luc Dauchet, Fred Paccaud, Paibul Suriyawongpaisal, Sherali Rakhmatulloev, Hyeon Chang Kim, Markku Peltonen, Ruth Frikke-Schmidt, Vera Musil, Ahmad Ali Zainuddin, Angela Chetrit, Dan Zhu, Gowri Mahasampath, Ulrich Keil, Sérgio Viana Peixoto, Haiquan Xu, Helle-Mai Loit, Valérie Deschamps, Ilpo Huhtaniemi, Lijuan Liu, Marialaura Bonaccio, Altan Onat, Rody G. Sy, José María Huerta, Ko Ko Zaw, Akihiro Yoshihara, Peter Ueda, Belgin Ünal, Rachel Dankner, Andrzej Wiecek, Eman Aly, Ruzena Kubinova, Justina Vaitkeviciute, Hanna Tolonen, Priscilla Duboz, Orn Olafsson, Yin Guo, Chiara Donfrancesco, Salim Mohanna, Dusan Grafnetter, Daniel Weghuber, Ali Ahmadi, Rosemary B. Duda, E. Shyong Tai, Louise A. Baur, Nihal Thomas, Prabhdeep Kaur, Norlaila Mustafa, Shariq Rashid Masoodi, Liis Nelis, Badreya Al-Lahou, J. Jaime Miranda, Lèlita Santos, Aroor Bhagyalaxmi, Mohamed Bamoshmoosh, Børge G. Nordestgaard, Jeannette Lee, Ahmad Reza Dorosty, Alain Morejon, Ying-Wei Wang, Jakob Tarp, Rosalba Rojas-Martínez, Luxia Zhang, Bahram Mohajer, Maja Bæksgaard Jørgensen, Jurate Klumbiene, Zhengming Chen, Ambady Ramachandran, Andrea Rodriguez-Martinez, Alisha N. Wade, Suyeon Park, Janne Schurmann Tolstrup, Lucjan Szponar, Krishna Kumar Aryal, Tahir Aris, Mahfuzar Rahman, Dorja Vočanec, Juan P. González-Rivas, Rob M. van Dam, Daniel Bia, Oonagh Markey, Ryutaro Ohtsuka, Kumiko Ohara, Ričardas Radišauskas, Jurate Medzioniene, Tiina Vlasoff, Tania Tello, Suzanne C. Ho, Kodavanti Mallikharjuna Rao, May Soe Aung, Vesselka Duleva, Michael Hobbs, Lutgarde Thijs, Marjolein Visser, Parasmani Dasgupta, Inge Huybrechts, Raimund Erbel, Alice Bonilla-Vargas, Hermann Brenner, Mohammad Reza Fattahi, Jolanda Hyska, Roman Topor-Madry, Ranjit Mohan Anjana, Merike Liivak, Eruke E. Egbagbe, Mathilde Savy, Herculina S. Kruger, Neil Murphy, Vinay Nangia, Cesar G. Victora, Mostafa K. Mohamed, H. Bas Bueno-de-Mesquita, Gabriella Gruden, Marcos André Moura-dos-Santos, Mohammed Rasoul Tarawneh, Maria Teresa Menzano, Francesco Branca, Abdonas Tamosiunas, Elena Bogova, Niveen M E Abu-Rmeileh, Maroje Sorić, Aleksander Giwercman, Elżbieta Dziankowska-Zaborszczyk, Tatjana Hejgaard, Yves Kameli, Margarita Samoutian, Andreia N. Pizarro, Jin Soo Moon, Frank Claessens, Zulfiqar A Bhutta, Frank Tanser, Nor Azwany Yaacob, Vanina Bongard, Gregor Jurak, Johan G. Eriksson, Christina-Paulina Lambrinou, Hanspeter Stamm, Kim Overvad, Yanping Li, Carsten Oliver Schmidt, Thomas Meinertz Dantoft, Wichai Aekplakorn, Anwar Batieha, Eduardo Capuano, Teresa Haugsgjerd, Jeremy M. Jacobs, Paola Russo, Nguyen D Nguyen, Luis Revilla, Hossein Poustchi, Farid Najafi, Giovanni de Gaetano, Wan Mohamad Wan Bebakar, Paul Elliott, Denise Eldemire-Shearer, Angela Döring, Giovanni Viegi, Xiaoguang Yang, María-Elena González-Villalpando, Maria Puiu, Maria Benedetta Donati, Andrew Wong, Tomasz Zdrojewski, Carlos P. Boissonnet, Mohamad Hasnan Ahmad, Mahmudur Rahman, Günther Fink, Marcia Makdisse, Dragana P Jovic, Aline Wagner, Coimbatore Subramaniam Shanthirani, Pascal Bovet, Dong Wook Kim, Tom Wilsgaard, Anders Grøntved, Thirunavukkarasu Sathish, Antonia Trichopoulou, Noushin Mohammadifard, Igor Spiroski, Natasja M. van Schoor, Cláudia S. Minderico, Betina H. Thuesen, Queenie Chan, Ulf Ekelund, Laura A. Rodríguez-Villamizar, Line Lund Kårhus, Cihangir Erem, Amina Barkat, Maria Paula Santos, Fernanda Cunha Soares, Constanta Huidumac Petrescu, Allan G. Hill, Honor Bixby, Benoît Salanave, Joana Carvalho, Maigeng Zhou, Ofra Kalter-Leibovici, Roy A Wong-McClure, Kim F. Michaelsen, Doris Stöckl, Rosalynn Siantar, Jouko Saramies, José R. Banegas, Quang Ngoc La, Uruwan Yamborisut, Parinaz Mehdipour, Farhad Pourfarzi, Sudha Ramachandra Rao, Katsuyasu Kouda, Chien-Jen Chen, Rafael dos Santos Henrique, Martin Nankap, Allan Linneberg, Ronald D. Gregor, Rudolf Kaaks, Maria do Carmo Franco, Marta García-Solano, Beata Gurzkowska, Bahman Cheraghian, Stefaan De Henauw, Daniel Ferrante, Johanna A. Otero, Jamila Abubakar Garba, Antonio Pedro Graça, Sumit Bharadwaj, Shiqi Zhen, Xiu-Hua Guo, Prashant Mathur, Raphael Mendes Ritti-Dias, Kouamelan Doua, Esteban Carmuega, Majid Shirani, Przemyslaw Slusarczyk, Petra Rust, Visnja Djordjic, Farahnaz Joukar, Johanna Gunnlaugsdottir, Leila Houti, Nayu Ikeda, Imperia Brajkovich, Amirabbas Momenan, Erik J. Timmermans, Marcin Rutkowski, Biruta Velika, Joana Araújo, Jostein Steene-Johannessen, Christa L. Lilly, Per Tynelius, Michael Tornaritis, Anne Juolevi, Fatima Zahra Laamiri, Carl Lachat, Kai-Uwe Saum, Espen Bjertness, Ana P. Ortiz, Joel G. R. Roy, Himanshu K. Chaturvedi, Michelle Holdsworth, Niels Wedderkopp, Johan Van der Heyden, Mukharram M. Bikbov, Hsien-Ho Lin, Eva Corpeleijn, Harshpal Singh Sachdev, Mohammad Reza Mirjalili, Maria del Cristo Rodriguez-Perez, Michala Lustigová, Tuyen D Le, Teresa Norat, Hana Zamrazilová, Garry Brian, Tien Yin Wong, Rosa Haghshenas, Clive Osmond, Diego Giulliano Destro Christofaro, Mahmood Moosazadeh, Vilma Irazola, Olli T. Raitakari, Marco Aurélio Peres, Terho Lehtimäki, Shuohua Chen, Dimitrios Papandreou, Robert J. Adams, Sigmund A. Anderssen, Peter T. Katzmarzyk, Luisa M Macieira, Félicité Tchibindat, Lital Keinan Boker, Toshiharu Ninomiya, Morten Sodemann, Jytte Halkjær, Zbigniew Kułaga, Sophie Visvikis-Siest, Farshad Farzadfar, N Capkova, Zumin Shi, Maria Turley, Zbigniew Gaciong, Giovanni Veronesi, Martin McKee, Veikko Salomaa, Gilad Twig, Elisabetta L. Romeo, Peter Kristensen, Grazyna Jasienska, Victor Guillermo Sequera, Mario V. Capanzana, Con Burns, Emanuela Pettenuzzo, Ming-Dong Wang, Jonathan Giovannelli, Stela McLachlan, Ellis Owusu-Dabo, Stefania Toselli, Maria Teresa Anselmo Olinto, Senthil K Vasan, Sara Schramm, Xenophon Theodoridis, Moyses Szklo, Ramfis Nieto-Martínez, Viswanathan Mohan, Guillermo Frontera, Rahul Malhotra, Thomas Ferrao, Dongfeng Gu, Tomas Vega, Hynek Pikhart, Päivi Mäki, Heba Fouad, Vilnis Dzerve, Christina Howitt, Seyed Mohammad Hashemi-Shahri, Jenny M. Kindblom, Marjolijn C. E. Bragt, G. K. Mini, Qian Wang, Liufu Cui, Andrzej Galbarczyk, Sylvain Sebert, Vilmundur Gudnason, Loreto Santa Marina, Kairat Davletov, Afshin Ostovar, Niloofar Peykari, Nicholas J. Wareham, Wilma M. Hopman, Karl-Heinz Jöckel, Jussi Kauhanen, Breige A. McNulty, Alina Kerimkulova, Youcef Laid, Claes Ohlsson, Stefan Kiechl, Alicia Matijasevich, Boban Mugoša, Srinivasan Kannan, Jyrki K. Virtanen, Mohan Deepa, Mangesh S. Pednekar, Shahla AlDhukair, Cynthia M. Pérez, Vera Lanska, Tint Swe Latt, Dominique Hange, João Luiz Bastos, Eliza Markidou Ioannidou, Leticia Hernandez Cadena, Maya Tanrygulyyeva, Reza Malekzadeh, Dimitrios Poulimeneas, Pedro Ordunez, Thomas Waldhör, Ioannis Pagkalos, Carlo M. Barbagallo, Abla M. Sibai, Peter Vollenweider, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Santosh K. Bhargava, Patrick Kolsteren, Aya Mostafa, Fangfang Chen, Flavio Nervi, Imre Janszky, Arvind Pandey, Renata Cifkova, Alexandre C. Pereira, Alejandro Diaz, Alireza Ansari-Moghaddam, Rachakulla Hari Kumar, Jaakko Mursu, Luis A. Moreno, Glen Gironella, Jelena Kos, Tilema Cama, Haakon E. Meyer, Jun Ma, Raphael E. Arku, Ziad Abdeen, Rusidah Selamat, Dianna J. Magliano, Jitendra Jonnagaddala, Konstantinos Gkiouras, Paul Korrovits, Paola Nardone, Paolo Vineis, Kotsedi D Monyeki, Khuong Quynh Long, Alberto Barceló, Camilla T. Damsgaard, Constance Schultsz, Frank J Rühli, Santiago F. Gomez, Tara Coppinger, Muhammad Islam, Pierre Traissac, Eleonora d'Orsi, Irfan Nuhoglu, Rui Providência, Bernard Maire, Leandra Abarca-Gómez, Sinead Brophy, Daniela Pierannunzio, Cristina Taddei, Wen-Harn Pan, Gregor Starc, Abdullah Alkandari, Saeed Dastgiri, Lien Braeckevelt, Gustavo Velasquez-Melendez, Sudhir Kowlessur, Bagher Larijani, Cynthia Robitaille, Mohamed M. Ali, Steiner Krokstad, Noor Ani Ahmad, Anar Dushpanova, Agustinus Soemantri, Susana Sans, Ionela Pascanu, Gwenaëlle Le Coroller, Inger Ariansen, Abhijit Sen, Sergej M. Ostojic, Silvana Donoso, Felix K. Assah, Juan A Rivera, Peter H. Whincup, Oana-Florentina Gheorghe-Fronea, Hanan F. Abdul Rahim, Yadlapalli S. Kusuma, Michael Knoflach, Moein Yoosefi, Cassiano Ricardo Rech, Paul Ferdinand M. Reganit, Tomi-Pekka Tuomainen, Francesco Gianfagna, Stefania Maggi, Mohammad Hossein Somi, Behrooz Hamzeh, Bethlehem D. Solomon, Herman Borghs, Zhanna Kalmatayeva, Heidi Klakk, Akram Pourshams, Naomi S. Levitt, Miquel Porta, Vesna Jureša, Alexander D. Deev, Son Thai Pham, Paula Margozzini, Silvia Bel-Serrat, Dora Romaguera, Monira Alarouj, Winsome R. Parnell, Marloes Cardol, David Faeh, Antonio Bernabe-Ortiz, Giota Touloumi, Maryam Kavousi, Sanja Musić Milanović, Jalila El Ati, Sauli Herrala, Liang Xu, Sirkka Keinänen-Kiukaanniemi, Ian Hambleton, Stefan Savin, Andre Pascal Kengne, R. Krishna Kumar, Kurt Widhalm, Marco M Ferrario, Parisa Amiri, Yi Song, Jianfeng Wu, Jeannette Klimont, Jean Ferrières, Farhad Zamani, Shina Avi, Luis Paulo Gomes Mascarenhas, Aluísio J D Barros, Reecha Sofat, Koen Van Herck, Hoang Van Minh, Enrique Gutiérrez-González, Martine Vrijheid, Susana Cararo Confortin, Antonis Zampelas, Bogdan Wojtyniak, Ausra Petrauskiene, Juha Auvinen, Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Young-Ho Khang, Ellina Rakhimova, Magdalena Klimek, Luís Lopes, Erkin M. Mirrakhimov, Maria Lc Iurilli, Günay Can, Mark Woodward, Esther Lopez-Garcia, Mauro Virgílio Gomes de Barros, Ahmed A. Madar, Rainford J. Wilks, Shoaib Afzal, Melanie J. Cowan, Gareth Stratton, Eduardo Salazar Martinez, Sameer Narake, Norie Sawada, Li Juan Wu, Adrian Richter, Licia Iacoviello, Hanno Ulmer, Deepak Amarapurkar, Mohsen Ibrahim, Hamed Pouraram, Massimo Salvetti, Hung-Kwan So, Yonghua Hu, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Sabina Zambon, Angelika Schaffrath Rosario, Lauren Lissner, Kamarul Imran Musa, Deepa Weerasekera, Bihungum Bista, Takafumi Ishida, Ekaterina Chikova-Iscener, Mirjam M. Heinen, Tazeen H. Jafar, Semánová Csilla, Raija Korpelainen, Edward W. Gregg, Laura Gutierrez, Victor M. Herrera, Aristides M. Machado-Rodrigues, Fatemeh Malekzadeh, Shouling Wu, Jennifer L. Baker, Clicerio González-Villalpando, Irene G. M. van Valkengoed, Anna Fijałkowska, Meghnath Dhimal, Murat Topbaş, George Moschonis, Robert Eggertsen, Quang Ngoc Nguyen, Janette Walton, Elnaz Faramarzi, Nasheeta Peer, Radka Taxová Braunerová, Harald Geiger, Morteza Shamshirgaran, Lela Shengelia, María Ángeles Dal Re Saavedra, Khem Bahadur Karki, Timothy J. Key, Maria G. Grammatikopoulou, Susana Vale, Bernhard O. Boehm, Songhomitra Panda-Jonas, Iveta Pudule, Elisabete Ramos, Lacramioara Aurelia Brinduse, Paul H. Lee, Terence W O'Neill, Javad Aghazadeh-Attari, Margus Punab, Bojan Jelaković, Eliza Cinteza, Ha Tp Do, and Alison J. Hayes
Subjects: education.field_of_study, business.industry, Population, Distribution (economics), medicine.disease, Obesity, Geography, medicine, Underweight, medicine.symptom, education, business, Body mass index, Demography
Published: 2020

26. Baseline and interim PET-based outcome prediction in peripheral T-cell lymphoma:A subgroup analysis of the PETAL trial

Author: Heinz Dürk, Arnold Ganser, Jan Rekowski, Andreas Hertel, Bernd Hertenstein, Lars Kurch, Matthias Sandmann, Winfried Brenner, Christiane Kreisel-Büstgens, Christiane Franzius, Wolfram Klapper, Matthias Weckesser, Aristoteles Giagounidis, Martin Freesmeyer, Thomas Krohn, Volker Runde, Dirk Behringer, Michael Heike, Stefan P. Müller, Frank Kroschinsky, Regina Moeller, Rolf Larisch, Hubertus Hautzel, Christine Schmitz, Gerhard Heil, Rolf M. Mesters, Ulrich Dührsen, Karl-Heinz Jöckel, Ferras Alashkar, Helga Bernhard, Dietmar Wacker, Uwe M. Martens, Stefan Mahlmann, Stefan Wilop, Jörg Kotzerke, Ronald Boellaard, Paul La Rosée, Gabriele Prange-Krex, Andreas Hüttmann, Heinz Gert Hoeffkes, Uwe Haberkorn, Guido Trenn, Dieter Hoelzer, Marcus Brinkmann, Frank M. Bengel, Radiology and nuclear medicine, and CCA - Imaging and biomarkers
Subjects: Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Adolescent, Population, Medizin, Standardized uptake value, Subgroup analysis, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Fluorodeoxyglucose F18, hemic and lymphatic diseases, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Anaplastic lymphoma kinase, Humans, Prospective cohort study, education, Aged, Aged, 80 and over, education.field_of_study, business.industry, Hazard ratio, Lymphoma, T-Cell, Peripheral, Hematology, General Medicine, Middle Aged, medicine.disease, Prognosis, Peripheral T-cell lymphoma, Lymphoma, Survival Rate, 030220 oncology & carcinogenesis, Positron-Emission Tomography, Female, Radiopharmaceuticals, business, 030215 immunology, Follow-Up Studies
Abstract: The prospective randomized Positron Emission Tomography (PET)-Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL) trial was designed to test the ability of interim PET (iPET) to direct therapy. As reported previously, outcome remained unaffected by iPET-based treatment changes. In this subgroup analysis, we studied the prognostic value of baseline total metabolic tumor volume (TMTV) and iPET response in 76 patients with T-cell lymphoma. TMTV was measured using the 41% maximum standardized uptake value (SUV41max) and SUV4 thresholding methods. Interim PET was performed after two treatment cycles and evaluated using the ΔSUVmax approach and the Deauville scale. Because of significant differences in outcome, patients with anaplastic lymphoma kinase (ALK)-positive lymphoma were analyzed separately from patients with ALK-negative lymphoma. In the latter, TMTV was statistically significantly correlated with progression-free survival, with thresholds best dichotomizing the population, of 232 cm3 using SUV41max and 460 cm3 using SUV4. For iPET response, the respective thresholds were 46.9% SUVmax reduction and Deauville score 1-4 vs 5. The proportion of poor prognosis patients was 46% and 29% for TMTV by SUV41max and SUV4, and 29% and 25% for iPET response by ΔSUVmax and Deauville, respectively. At diagnosis, the hazard ratio (95% confidence interval) for poor prognosis vs good prognosis patients according to TMTV was 2.291 (1.135-4.624) for SUV41max and 3.206 (1.524-6.743) for SUV4. At iPET, it was 3.910 (1.891-8.087) for ΔSUVmax and 4.371 (2.079-9.187) for Deauville. On multivariable analysis, only TMTV and iPET response independently predicted survival. Patients with high baseline TMTV and poor iPET response (22% of the population) invariably progressed or died within the first year (hazard ratio, 9.031 [3.651-22.336]). Due to small numbers and events, PET did not predict survival in ALK-positive lymphoma. Baseline TMTV and iPET response are promising tools to select patients with ALK-negative T-cell lymphoma for early allogeneic transplantation or innovative therapies.
Published: 2020

27. Psychological burden of healthcare professionals in Germany during the acute phase of the COVID-19 pandemic: differences and similarities in the international context

Author: Madeleine Hetkamp, Benjamin Weismüller, Florian Junne, Andreas Stang, Karl-Heinz Jöckel, Eva-Maria Skoda, Adam Schweda, Alexander Bäuerle, Martin Teufel, Venja Musche, Hannah Kohler, and Nora Dörrie
Subjects: Adult, Male, medicine.medical_specialty, Generalized anxiety disorder, Coronavirus disease 2019 (COVID-19), Health Personnel, generalized anxiety, Medizin, Context (language use), Vulnerable Populations, information, German, 03 medical and health sciences, 0302 clinical medicine, Germany, Pandemic, Medicine, Humans, AcademicSubjects/MED00860, 030212 general & internal medicine, Psychiatry, Pandemics, Depression (differential diagnoses), Psychiatric Status Rating Scales, Health professionals, psychological burden, business.industry, SARS-CoV-2, Mental Disorders, Public Health, Environmental and Occupational Health, COVID-19, General Medicine, healthcare professionals, medicine.disease, language.human_language, Generalized anxiety, Cross-Sectional Studies, language, Original Article, Female, business, 030217 neurology & neurosurgery
Abstract: Background Healthcare professionals (HPs) are the key figures to keep up the healthcare system during the COVID-19 pandemic and thus are one of the most vulnerable groups in this. To this point, the extent of this psychological burden, especially in Europe and Germany, remains unclear. This is the first study investigating German HPs after the COVID-19 outbreak. Methods We performed an online-based cross-sectional study after the COVID-19 outbreak in Germany (10–31 March 2020). In total, 2224 HPs (physicians n = 492, nursing staff n = 1511, paramedics n = 221) and 10 639 non-healthcare professionals (nHPs) were assessed including generalized anxiety (Generalized Anxiety Disorder-7), depression (Patient Health Questionnaire-2), current health status (EQ-5D-3L), COVID-19-related fear, subjective level of information regarding COVID-19. Results HPs showed less generalized anxiety, depression and COVID-19-related fear and higher health status and subjective level of information regarding COVID-19 than the nHPs. Within the HP groups, nursing staff were the most psychologically burdened. Subjective levels of information regarding COVID-19 correlated negatively with generalized anxiety levels across all groups. Among HPs, nursing staff showed the highest and paramedics the lowest generalized anxiety levels. Conclusions In the context of COVID-19, German HPs seem to be less psychological burdened than nHPs, and also less burdened compared with existing international data.
Published: 2020

28. Seasonality of non-SARS, non-MERS Corona viruses and the impact of meteorological factors

Author: Ulf Dittmer, Andreas Stang, Fotis Theodoropoulos, Karl-Heinz Jöckel, Johannes Korth, Olympia E. Anastasiou, Anika Hüsing, and Christian Taube
Subjects: endocrine system, Cloud cover, medicine, Environmental science, Relative humidity, Precipitation, Seasonality, medicine.disease, Atmospheric sciences, Logistic regression, Corona, Virus, Virus detection
Abstract: BackgroundSeasonality is a characteristic of some respiratory viruses. The aim of our study was to evaluate the seasonality and the potential effects of different meteorological factors on the detection rate of the non-SARS Corona Virus detection by PCR.MethodsWe performed a retrospective analysis of 12763 respiratory tract sample results (288 positive and 12475 negative) for non-SARS, non-MERS Corona viruses (NL63, 229E, OC43, HKU1). The effect of seven single weather factors on the Corona virus detection rate was fitted in a logistic regression model with and without adjusting for other weather factors.ResultsCorona virus infections followed a seasonal pattern peaking from December to March and plunging from July to September. The seasonal effect was less pronounced in immunosuppressed patients compared to immunocompetent. Different automatic variable selection processes agreed to select the predictors temperature, relative humidity, cloud cover and precipitation as remaining predictors in the multivariable logistic regression model including all weather factors, with low ambient temperature, low relative humidity, high cloud cover and high precipitation being linked to increased Corona virus detection rates.ConclusionsCorona virus infections followed a seasonal pattern, which was more pronounced in immunocompetent patients compared to immunosuppressed. Several meteorological factors were associated with the Corona virus detection rate. However, when mutually adjusting for all weather factors, only temperature, relative humidity, precipitation and cloud cover contributed independently to predicting the Corona virus detection rate.
Published: 2020
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29. Defective migration and dysmorphology of neutrophil granulocytes in atypical chronic myeloid leukemia treated with ruxolitinib

Author: Lea Bornemann, Matthias Gunzer, Thomas Haverkamp, Karl-Heinz Jöckel, Marc Schuster, Clara Bessen, Simon F. Merz, Joachim R. Göthert, Charlyn Sobczak, and Saskia Schmitz
Subjects: Male, 0301 basic medicine, Cancer Research, Ruxolitinib, Myeloid, Neutrophils, Neutrophil granulocyte, Medizin, Video microscopy, CD16, Cell morphology, lcsh:RC254-282, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, aCML, Nitriles, Case report, Biomarkers, Tumor, Genetics, medicine, Humans, Longitudinal Studies, Aged, Standardized migration analysis, business.industry, Neutrophil granulocytes, High-Throughput Nucleotide Sequencing, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Leukemia, Pyrimidines, 030104 developmental biology, medicine.anatomical_structure, Oncology, Case-Control Studies, 030220 oncology & carcinogenesis, Immunology, Atypical chronic myeloid leukemia, Pyrazoles, Female, business, Research Article, Granulocytes, medicine.drug
Abstract: Background The identification of pathologically altered neutrophil granulocyte migration patterns bears strong potential for surveillance and prognostic scoring of diseases. We recently identified a strong correlation between impaired neutrophil motility and the disease stage of myelodysplastic syndrome (MDS). Here, we apply this assay to study quantitively increased neutrophils of a patient suffering from a rare leukemia subtype, atypical chronic myeloid leukemia (aCML). Methods A 69-year-old male was analyzed in this study. Besides routine analyses, we purified the patient’s neutrophils from peripheral whole blood and studied their migration behavior using time-lapse video microscopy in a standardized assay. These live cell migration analyses also allowed for the quantification of cell morphology. Furthermore, the cells were stained for the markers CD15, CD16, fMLPR, CXCR1 and CXCR2. Results Despite cytoreductive therapy with hydroxyurea, the patient’s WBC and ANC were poorly controlled and severe dysgranulopoiesis with hypogranularity was observed. Neutrophils displayed strongly impaired migration when compared to healthy controls and migrating cells exhibited a more flattened-out morphology than control neutrophils. Because of a detected CSF3R (p.T618I) mutation and constitutional symptoms treatment with ruxolitinib was initiated. Within 1 week of ruxolitinib treatment, the cell shape normalized and remained indistinguishable from healthy control neutrophils. However, neutrophil migration did not improve over the course of ruxolitinib therapy but was strikingly altered shortly before a sinusitis with fever and bleeding from a gastric ulcer. Molecular work-up revealed that under ruxolitinib treatment, the CSF3R clone was depleted, yet the expansion of a NRAS mutated subclone was promoted. Conclusion These results demonstrate the usefulness of neutrophil migration analyses to uncover corresponding alterations of neutrophil migration in rare myeloid neoplasms. Furthermore, in addition to monitoring migration the determination of morphological features of live neutrophils might represent a useful tool to monitor the effectiveness of therapeutic approaches.
Published: 2020

30. Comparison of early tumour-associated versus late deaths in patients with central or7 cm T4 N0/1 M0 non-small-cell lung-cancer undergoing trimodal treatment: Only few risks left to improve

Author: Georgios Stamatis, Nika Guberina, Clemens Aigner, Thomas Gauler, Martin Stuschke, Maja Guberina, Dirk Theegarten, Wilfried Eberhardt, Kaid Darwiche, Martin Metzenmacher, Martin Schuler, Christoph Pöttgen, Till Plönes, Karl-Heinz Jöckel, and Bettina Krebs
Subjects: 0301 basic medicine, Adult, Male, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Time Factors, Medizin, Mediastinoscopy, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Carcinoma, Non-Small-Cell Lung, medicine, Humans, Stage (cooking), Lung cancer, Pneumonectomy, Survival analysis, Aged, Neoplasm Staging, Retrospective Studies, medicine.diagnostic_test, business.industry, Mortality rate, Hazard ratio, Induction chemotherapy, Chemoradiotherapy, Adjuvant, Induction Chemotherapy, Middle Aged, medicine.disease, Comorbidity, Neoadjuvant Therapy, Tumor Burden, 030104 developmental biology, Treatment Outcome, Oncology, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, business
Abstract: Background The optimal treatment for patients with locally advanced non-small-cell lung-cancer (NSCLC) cT4 cN0/1 cM0 is still under debate. The purpose of this study was to examine the long-term survival of cT4 cN0/1 cM0 NSCLC patients undergoing induction chemotherapy and concurrent radiochemotherapy before surgery. Methods All consecutive patients with confirmed NSCLC (cT4 cN0/1 cM0) treated with neoadjuvant chemotherapy, concurrent radiochemotherapy (RT/CTx) (45–46 Gy) and surgical resection between 2000 and 2015 were included. According to the UICC guidelines (8th edition), T4 stage was reanalysed by an expert radiologist. The mediastinal staging was performed by systematic EBUS-TBNA or mediastinoscopy. The primary end-point was overall-survival (OS). The power to detect an increase of early tumour-associated mortality (hazard ratio > 3.5) within the first 5 years after treatment in comparison to late deaths beyond 96 months was >80%. Results Overall, 67 patients were treated with concurrent RT/CTx. T4 criteria were fulfilled by all patients, and multiple T4 criteria by 53 patients. Seventy percent of patients had an initial PET/CT staging. The median follow-up period was 134 months. OS rates at 2, 5, 10 and 15 years were 83.6 ± 4.5%, 65.4 ± 5.9%, 53.3 ± 6.3% and 36.6 ± 6.8%, respectively. A total of 44.8% of patients achieved a pathologic complete response. In multivariable analysis, ypT category was the most predictive factor. OS at 5 years for ypT0 (n = 31) was 80.5%, and ypT1 (n = 11) was 62.5%. Main sites of failure were brain and pulmonary metastases in seven and three patients, respectively. The intercurrent annual death rate was estimated from the survival curve beyond 96 months and was found to be 4.75% (95% CI 2.40–9.27%). No significant increased mortality was observed during the first 5 years (annual death rate: 8.31% [95% CI 5.60–12.24%], hazard-ratio = 1.72 [95% CI 0.81–3.65]). Conclusions The effectiveness of this trimodality schedule is high in patients with cT4 cN0/1 cM0 NSCLC with excellent local control rates. Considering the annual death rate beyond 8 years of survival as an intercurrent death rate due to comorbidity, this treatment schedule reduces annual mortality to background even in the first 5 years after therapy.
Published: 2020

31. Characteristics of COVID-19 pandemic and public health consequences

Author: Fabian Standl, Andreas Stang, and Karl-Heinz Jöckel
Subjects: medicine.medical_specialty, 2019-20 coronavirus outbreak, biology, Coronavirus disease 2019 (COVID-19), Viral Epidemiology, business.industry, SARS-CoV-2, Public health, Pneumonia, Viral, MEDLINE, COVID-19, medicine.disease, biology.organism_classification, Pneumonia, Betacoronavirus, Pandemic, medicine, Humans, Public Health, Cardiology and Cardiovascular Medicine, Intensive care medicine, business, Coronavirus Infections, Pandemics
Published: 2020

32. Mapping Patient Data to Colorectal Cancer Clinical Algorithms for Personalized Guideline-Based Treatment

Author: Matthias Becker, Andreas Paul, Britta Böckmann, Isabel Virchow, Martin Stuschke, Stefan Kasper, and Karl-Heinz Jöckel
Subjects: 020205 medical informatics, Colorectal cancer, Medizin, Health Informatics, Context (language use), 02 engineering and technology, Health informatics, 03 medical and health sciences, 0302 clinical medicine, Clinical pathway, Health Information Management, 0202 electrical engineering, electronic engineering, information engineering, medicine, Humans, 030212 general & internal medicine, Precision Medicine, Point of care, Natural Language Processing, Neoplasm Staging, business.industry, Cancer, Guideline, medicine.disease, Precision medicine, Computer Science Applications, Practice Guidelines as Topic, business, Colorectal Neoplasms, Algorithm, Algorithms, Medical Informatics
Abstract: Background Colorectal cancer is the most commonly occurring cancer in Germany, and the second and third most commonly diagnosed cancer in women and men, respectively. In this context, evidence-based guidelines positively impact the quality of treatment processes for cancer patients. However, evidence of their impact on real-world patient care remains unclear. To ensure the success of clinical guidelines, a fast and clear provision of knowledge at the point of care is essential. Objectives The objectives of this study are to model machine-readable clinical algorithms for colon carcinoma and rectal carcinoma annotated by Unified Medical Language System (UMLS) based on clinical guidelines and the development of an open-source workflow system for mapping clinical algorithms with patient-specific information to identify patient's position on the treatment algorithm for guideline-based therapy recommendations. Methods This study qualitatively assesses the therapy decision of clinical algorithms as part of a clinical pathway. The solution uses rule-based clinical algorithms, which were developed based on the corresponding guidelines. These algorithms are executed on a newly developed open-source workflow system and are visualized at the point of care. The aim of this approach is to create clinical algorithms based on an established business process standard, the Business Process Model and Notation (BPMN), which is annotated by UMLS terminologies. The gold standard for the validation process was set by manual extraction of clinical datasets from 86 rectal cancer patients and 89 colon cancer patients. Results Using this approach, the algorithm achieved a precision value of 87.64% for colon cancer and 84.70% for rectal cancer with recall values of 87.64 and 83.72%, respectively. Conclusion The results indicate that the automatic positioning of a patient on the decision pathway is possible with tumor stages that have a less complex clinical algorithm with fewer decision points reaching a higher accuracy than complex stages.
Published: 2020

33. Long-term exposure to ambient source-specific particulate matter and its components and incidence of cardiovascular events - The Heinz Nixdorf Recall study

Author: Frauke Hennig, Simone Ohlwein, Barbara Hoffmann, U. Slomiany, Dirk M. Hermann, Vanessa J. Soppa, Sarah Lucht, Raimund Erbel, Vitalijs Rodins, Susanne Moebus, Sara Schramm, Karl-Heinz Jöckel, and Christian Weimar
Subjects: Male, 010504 meteorology & atmospheric sciences, Population, Medizin, 010501 environmental sciences, 01 natural sciences, Interquartile range, Environmental health, Air Pollution, Germany, medicine, Humans, Prospective Studies, education, Prospective cohort study, Stroke, Components, lcsh:Environmental sciences, 0105 earth and related environmental sciences, General Environmental Science, lcsh:GE1-350, education.field_of_study, Air Pollutants, business.industry, Incidence (epidemiology), Incidence, Hazard ratio, Environmental Exposure, medicine.disease, Confidence interval, Cardiovascular health, Coronary heart disease, Cohort, Female, Particulate Matter, business
Abstract: Background Few studies have examined the risk of long-term exposure to source-specific airborne pollutants on incidence of cerebrovascular and cardiovascular events. Objectives We aimed to estimate the effect of long-term exposure to source-specific air pollution and particulate matter (PM) components on incidence of stroke, coronary heart disease (CHD), and total cardiovascular events (CVE) in the population-based Heinz Nixdorf Recall study (HNR). Methods We used baseline (2000–2003) and 14-year follow-up data of the HNR Study, an ongoing population-based prospective cohort study in Western Germany. Participants’ residential mean exposures to NO2 and total and source-specific PM10, PM2.5, accumulation mode particle number concentration (PNAM), and PM components were modelled using a dispersion and chemical transport model. We used Cox regression to evaluate the effect of pollutants (per 1 μg/m3 increase and per interquartile range – IQR) on risk of stroke and CHD, adjusting for socio-demographic characteristics, lifestyle risk factors and nighttime traffic noise exposure. Results In 4,105 included participants (aged 45–76 at baseline, 52.5% women), we observed 118 cases of first stroke and 373 cases of first CHD during 46,748 person-years under risk. The median survival time within the cohort was 13.3 years. No effect of exposure to ambient air pollution on risk of CHD was observed, but distinct effects were observed for stroke. Ambient traffic-specific PM showed a stronger effect on stroke than industry-specific PM: hazard ratios (95% confidence interval) for total, traffic-specific, and industry-specific PM2.5 were 1.16 (1.02–1.34), 2.53 (1.07–5.97), and 1.27 (1.03–1.56) per 1 μg/m3 increase, respectively. PM components showed no substantially different effects from those of total PM per IQR, but higher associations were observed for NH4 and SO4 per 1 μg/m3. However, the exposure contrast of ammonium and sulfate components was very low. Conclusion Traffic-specific PM exhibited stronger effects than total and industry-specific PM on risk of stroke. Among components, NH4 and SO4 showed higher effects. No effect was observed for PM and CHD.
Published: 2020

34. The impact of RB1 genotype on incidence of second tumours in heritable retinoblastoma

Author: Börge Schmidt, Isabel Hülsenbeck, Karl-Heinz Jöckel, Mirjam Frank, Dietmar R. Lohmann, and Petra Ketteler
Subjects: 0301 basic medicine, Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Neoplasms, Radiation-Induced, Adolescent, Genotype, medicine.medical_treatment, Retinal Neoplasms, Medizin, Retinoblastoma Protein, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Gene Frequency, Internal medicine, Germany, medicine, Humans, In patient, Genetic Predisposition to Disease, Child, Retinoblastoma, business.industry, Incidence (epidemiology), Incidence, fungi, Neoplasms, Second Primary, Middle Aged, medicine.disease, Penetrance, eye diseases, Confidence interval, Radiation therapy, 030104 developmental biology, 030220 oncology & carcinogenesis, Child, Preschool, Female, Sarcoma, business, Follow-Up Studies
Abstract: Patients with heritable retinoblastoma are at risk for bilateral retinoblastoma and second primary malignancies (SPMs). The incidence of SPM is significantly raised after radiotherapy. We analysed the impact of the class of constitutional RB1 variant on the incidence of SPM in survivors with and without previous radiotherapy.From 1940 to 2008, 655 national patients were treated for heritable retinoblastoma at the German referral centre. Data on SPM, therapy and constitutional RB1 variant were available for 317 patients (48.3%). Heterozygous RB1 variants were classified into variants with regular and incomplete penetrance for retinoblastoma.SPM occurred in 51 of 317 survivors of heritable retinoblastoma. The incidence rate (IR) of SPM per 1000 person years was 8.4 (95% confidence interval (CI): 6.3-11.1) in individuals heterozygous for an oncogenic RB1 variant and 2.1 (95% CI: 0.0-11.4) with RB1 mosaicism. The incidence of SPM was higher in patients with regular penetrance compared with incomplete penetrance RB1 variants (IR 10.3 [95% CI: 7.5-13.8] vs. IR 3.2 [95% CI: 1.0-7.5]; p 0.05). In the subgroup without previous radiotherapy SPM were only observed in patients with regular penetrance variants (IR 6.3 [95% CI: 3.0-11.5]). Carriers of incomplete penetrance variants developed similar tumour entities as those with regular penetrance.Patients heterozygous for regular penetrance RB1 variants had a higher risk to develop SPM than patients with incomplete penetrance variants. Increased knowledge on genotype-phenotype relation regarding SPM may influence screening recommendations for SPM in survivors of heritable retinoblastoma.
Published: 2020

35. Fertility preservation and fulfillment of parenthood after treatment of hematological malignancies : results from the ‘Aftercare in Blood Cancer Survivors’ (ABC) study

Author: Ulrich Dührsen, Dietrich W. Beelen, Karl-Heinz Jöckel, Hildegard Lax, Christine Schmitz, Nils Lehmann, Julia Baum, and Tanja Gromke
Subjects: Infertility, Adult, Male, Pediatrics, medicine.medical_specialty, Allogeneic transplantation, Treatment-related infertility, Adolescent, media_common.quotation_subject, Medizin, Aftercare, Fertility, Blood cancer, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Cancer Survivors, Hematological malignancy, Surgical oncology, Surveys and Questionnaires, medicine, Humans, Fertility preservation, media_common, Aged, business.industry, Fertility Preservation, Posttreatment parenthood, Hematology, General Medicine, Middle Aged, medicine.disease, Oncology, 030220 oncology & carcinogenesis, Childlessness, Hematologic Neoplasms, Surgery, Female, Original Article, business, 030215 immunology, Cohort study
Abstract: Purpose Treatment of hematological malignancies carries the risk of lasting sterility. We aimed to identify fertility-related unmet needs. Methods The ‘Aftercare in Blood Cancer Survivors’ study is a cohort study of hematological patients who were in treatment-free remission for ≥ 3 years or stable under continuous oral medication. Female patients age 18–45 years and male patients age 18–65 years without a history of pre-treatment infertility were asked to answer a structured questionnaire including questions addressing fertility issues. Multivariable analyses were performed to detect risk factors. Results Of 1562 study participants, 1031 met the inclusion criteria for the fertility sub-study. A high proportion of patients (72.4%) received information about the risk of losing fertility, but only a minority (15%) took steps to preserve it. Female and older patients were less likely to be informed. A post-treatment wish for parenthood was expressed by 19.3% of patients. It was strongly associated with childlessness at time of diagnosis and could be fulfilled by 29.4%. Fulfillment of desired parenthood increased with increasing time from diagnosis and was low after allogeneic transplantation. Conclusions Female and older hematological patients are less likely to be informed about fertility-related issues than other patients. With societal changes towards first parenthood at higher age, the proportion of patients desiring a child after treatment is likely to increase. Fulfillment of desired parenthood remains challenging, especially after allogeneic transplantation. Implications for cancer survivors In patients likely to express a wish for post-treatment parenthood, fertility-related issues should routinely be addressed before gonadotoxic treatment is started.
Published: 2020

36. Occurrence of bronchial asthma and age at initial asthma diagnosis : First results of the German National Cohort

Author: Tobias Pischon, Alexander Kluttig, Rudolf Kaaks, Karin B. Michels, Klaus Berger, Tamara Schikowski, Efrat L. Amitay, Claudia Meinke-Franze, Oliver Kuß, Yvonne Kemmling, Karin Halina Greiser, Julia Fricke, Stefanie Castell, Wolfgang Ahrens, Stefan Karrasch, Sabina Waniek, Cornelia Gottschick, Thomas Keil, Börge Schmidt, Rafael T. Mikolajczyk, Markus Löffler, Korbinian Weigl, Johannes Horn, Nicole Legath, Annika Jagodzinski, Lina Jaeschke, Karl-Heinz Jöckel, Michael F. Leitzmann, Sabine Schipf, Holger Schulz, Heiko Becher, Wolfgang Lieb, Kathrin Günther, Hansjörg Baurecht, Claus-Werner Franzke, Kerstin Wirkner, Jakob Linseisen, Heinz-Erich Wichmann, and Susan Langer
Subjects: Gynecology, medicine.medical_specialty, Chronic diseases, General population, Cohort study, Respiratorische Erkrankung, Asthma, Kohortenstudie, Respiratory diseases, Chronische Erkrankungen, Allgemeinbevölkerung, business.industry, Public Health, Environmental and Occupational Health, Medizin, medicine.disease, National cohort, Chronic Diseases, Cohort Study, General Population, Respiratory Diseases, 03 medical and health sciences, 0302 clinical medicine, Chronic disease, 030228 respiratory system, medicine, ddc:610, 030212 general & internal medicine, business
Abstract: BACKGROUND: Asthma is one of the most common chronic diseases in both children and adults. Asthma first occurring in adulthood (adult-onset asthma, AOA) is associated with poorer prognosis compared to childhood-onset asthma (COA), which urgently calls for more research in this area. The aim of this work was to analyze the data on asthma collected in the German National Cohort and compare it with the German Health Interview and Examination Survey for Adults (DEGS), in particular regarding AOA. MATERIAL AND METHODS: Our analysis was based on the dataset of the main questionnaire at mid-term of the German National Cohort baseline examination, comprising 101,723 participants. Variables considered in the analyses were self-reported diagnosis of asthma, age at first diagnosis, asthma treatment in the past 12 months, age, and sex. RESULTS: In the midterm dataset, 8.7% of women and 7.0% of men in the German National Cohort reported that they had ever been diagnosed with asthma. Approximately one third of participants with asthma received their initial diagnosis before their 18th birthday. COA affected 2.2% of women and 2.8% of men, whereas AOA affected 6.5% of women and 4.2% of men. During the previous 12 months, 33% of COA cases and 60% of AOA cases were medically treated. CONCLUSION: The proportion of persons affected by asthma in the German National Cohort, as well as observed patterns regarding age and gender, corresponds to other data sources such as DEGS. However, in our analysis, the proportion of individuals with AOA was higher than described in the literature. The increase in cumulative asthma diagnoses with age is markedly steeper in younger participants, indicating a rising trend over time. HINTERGRUND: Asthma bronchiale stellt über alle Bildungsschichten hinweg eine der häufigsten chronischen Erkrankungen im Kindes- und Erwachsenenalter dar. Im Erwachsenenalter erstmals auftretendes Asthma (Adult-onset Asthma, AOA) ist im Vergleich zu Childhood-onset Asthma (COA) mit einer schlechteren Prognose assoziiert, was verstärkte Untersuchungen in diesem Bereich erfordert. Ziel der Arbeit war es, Häufigkeiten und das Alter bei Erstdiagnose aus Selbstangaben zu Asthma bei Erwachsenen in der NAKO Gesundheitsstudie darzustellen und mit Daten der Studie zur Gesundheit Erwachsener in Deutschland (DEGS) zu vergleichen. MATERIAL UND METHODEN: Unsere Analyse beruht auf einem Datensatz zur Halbzeit der NAKO-Basiserhebung mit 101.284 Personen. Verwendete Variablen waren die Selbstangabe zum jemals ärztlich diagnostizierten Asthma, Alter bei Erstdiagnose, Behandlung in den letzten 12 Monaten, Alter und Geschlecht. ERGEBNISSE: Laut Datenbasis zur Halbzeit berichteten in der NAKO 8,7 % der Frauen und 7,0 % der Männer, dass bei ihnen jemals Asthma diagnostiziert wurde. Etwa bei einem Drittel der Teilnehmenden mit Asthma wurde die Diagnose bereits im Kindes‑/Jugendalter (
Published: 2020

37. Long-term exposure to airborne particulate matter and NO 2 and prevalent and incident metabolic syndrome – Results from the Heinz Nixdorf Recall Study

Author: Hermann Jakobs, Frauke Hennig, Karl-Heinz Jöckel, Barbara Hoffmann, Susanne Moebus, Simone Ohlwein, Sarah Lucht, and Clara Matthiessen
Subjects: medicine.medical_specialty, Population, Medizin, 030204 cardiovascular system & hematology, 010501 environmental sciences, 01 natural sciences, Elevated blood, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, Epidemiology, medicine, education, lcsh:Environmental sciences, 0105 earth and related environmental sciences, General Environmental Science, lcsh:GE1-350, education.field_of_study, business.industry, Incidence (epidemiology), Odds ratio, medicine.disease, Obesity, Metabolic syndrome, business
Abstract: Introduction: Recently, epidemiological studies have found a link between air pollution (AP) and individual components of the metabolic syndrome (MetS), a condition predisposing to cardiometabolic diseases. However, very few studies have explored a possible association between air pollution and MetS. Objective: We analyzed the effects of long-term exposure to airborne particulate matter and NO2 on prevalence and incidence of MetS. Methods: We used data of the population-based prospective Heinz Nixdorf Recall study (baseline 2000–2003) to investigate the association(s) between AP exposure and MetS prevalence at baseline (n = 4457) and MetS incidence at first follow-up visit (n = 3074; average follow-up: 5.1 years). Mean annual exposure to size-fractioned particulate matter (PM10, PM2.5, PMcoarse, and PM2.5abs) and nitrogen dioxide (NO2) was assessed using a land use regression model. MetS was defined as central obesity plus two out of four additional risk factors (i.e., elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure or elevated plasma glucose). We estimated odds ratios (ORs) of MetS prevalence and incidence per interquartile range (IQR) of exposure, adjusting for demographic and lifestyle variables. Results: We observed a MetS prevalence of 20.7% (n = 922) and an incidence of 9.7% (n = 299). NO2 was positively associated with MetS prevalence, with an OR increase per IQR of 1.12 (95%-CI 1.02–1.24, IQR = 6.1 μg/m3). PM10 and PM2.5 were both borderline positively associated with MetS incidence, with ORs of 1.14 (95%-CI 0.99–1.32, IQR = 2.1 μg/m3) and 1.19 (95%-CI 0.98–1.44, IQR = 1.5 μg/m3) per IQR, respectively. Conclusion: In summary, we found a weak positive association between air pollution and MetS. The strongest and most consistent effects were observed between NO2 and prevalent MetS. Keywords: Air pollution, Particulate matter, NO2, Metabolic syndrome, Noise, Epidemiology
Published: 2018

38. Occupational exposure to organic solvents and risk of male breast cancer: a European multicenter case-control study

Author: Lorenzo Richiardi, Diane Cyr, Wolfgang Ahrens, Elsebeth Lynge, Franco Merletti, Nasser Laouali, Monica Neri, Linda Kaerlev, Mikael Eriksson, Corinne Pilorget, María Morales-Suárez-Varela, Noemia Afonso, Giuseppe Gorini, Karl-Heinz Jöckel, Pascal Guénel, Agustin Llopis-González, Jørn Olsen, Svend Sabroe, Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), Population-based Epidemiologic Cohorts Unit, Inserm, Villejuif, France, parent, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark, Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark, Occupational & Environmental Epidemiology Section, Cancer Research & Prevention Institute (ISPO), Florence, Italy, Department of Medical Sciences [Turin, Italy] (DMS), Università degli studi di Torino = University of Turin (UNITO), Unit of Public Health and Environmental Care, Department of Preventive Medicine, University of Valencia, Burjassot, Valencia, Spain, CIBER de Epidemiología y Salud Pública (CIBERESP), Institute for Prevention Research and Epidemiology, BIPS-Institute for Epidemiology and Prevention Research GmbH, Bremen, Germany, Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany, Centro Hospitalar do Porto, Porto, Portugal, Department of Oncology, Skane University Hospital, Lund, Sweden, Skane University Hospital [Lund], Department of Public Health, University of Copenhagen, Copenhagen, Denmark, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and University of Turin
Subjects: Male, european, BENZENE, trichloroethylene, Medizin, Cumulative Exposure, ethylene glycol, male breast cancer, jem, benzene, 0302 clinical medicine, Risk Factors, Surveys and Questionnaires, multicenter case-control study, POPULATION, Incidence, Incidence (epidemiology), WOMEN, WORKERS, job-exposure matrix, Middle Aged, 030210 environmental & occupational health, 3. Good health, Europe, Occupational Diseases, Occupational Diseases/chemically induced, Solvents/toxicity, 030220 oncology & carcinogenesis, Male breast cancer, organic solvent, petroleum solvent, Public aspects of medicine, RA1-1270, Adult, medicine.medical_specialty, Ethylene Glycol/toxicity, TRICHLOROETHYLENE, case-control study, Job-exposure matrix, ENDOCRINE-DISRUPTING CHEMICALS, chlorinated solvent, Trichloroethylene/toxicity, Breast Neoplasms, Male, Europe/epidemiology, 03 medical and health sciences, Breast cancer, breast cancer, Internal medicine, medicine, Humans, COHORT, Benzene/toxicity, Retrospective Studies, Aged, business.industry, ETHYLENE-GLYCOL ETHERS, MORTALITY, Occupational Exposure/adverse effects, Public Health, Environmental and Occupational Health, Case-control study, OXIDE, Retrospective cohort study, Odds ratio, occupational exposure, Breast Neoplasms, Male/chemically induced, medicine.disease, JEM, Logistic Models, Case-Control Studies, alcoholic solvent, Solvents, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Objectives The etiology of male breast cancer (MBC) is largely unknown but a causal role of exposure to organic solvents has been suggested. Previous studies on occupational risk factors of breast cancer were often restricted to women who are frequently exposed to lower levels and at a lower frequency than men. We investigated the association between MBC and occupational exposure to petroleum and oxygenated and chlorinated solvents in a multicenter case-control study of rare cancers in Europe. Methods The study included 104 MBC cases and 1901 controls. Detailed lifetime work history was obtained during interviews, together with sociodemographic characteristics, medical history and lifestyle factors. Occupational exposures to solvents were estimated from a job-exposure matrix. Odds ratios (OR) and their 95% confidence intervals (CI) were calculated using unconditional logistic regression models. Results Lifetime cumulative exposure to trichloroethylene >23.9 ppm years was associated with an increased MBC risk, compared to non-exposure [OR (95% CI): 2.1 (1.2-4.0); P trend
Published: 2018

39. 25-Hydroxvitamin D concentrations are not lower in children with bronchial asthma, atopic dermatitis, obesity, or attention-deficient/hyperactivity disorder than in healthy children

Author: Mirjam Frank, Cordula Koerner-Rettberg, Katharina Radkowski, Börge Schmidt, Stephanie Gest, Eckard Hamelmann, Karl-Heinz Jöckel, Thomas Reinehr, Tanja Legenbauer, Christian Langrock, Thomas Lücke, and Martin Holtmann
Subjects: Male, Pediatric Obesity, Endocrinology, Diabetes and Metabolism, Medizin, Physiology, Parathyroid hormone, 030209 endocrinology & metabolism, Disease, Body Mass Index, Dermatitis, Atopic, Bone remodeling, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Forced Expiratory Volume, Vitamin D and neurology, Humans, Medicine, Attention, 030212 general & internal medicine, Vitamin D, Child, Asthma, Nutrition and Dietetics, business.industry, Atopic dermatitis, Vitamin D Deficiency, medicine.disease, Obesity, Attention Deficit Disorder with Hyperactivity, Parathyroid Hormone, Case-Control Studies, Female, Cognition Disorders, business, Body mass index
Abstract: Vitamin D (vitD) is involved in immune regulation, and its receptor has been identified in several tissues including lung, adipose tissue, brain, and skin. Based on these observations, it has been suggested that vitD has an essential role not only in bone metabolism but also in other diseases such as atopic dermatitis (AD), bronchial asthma (BA), attention-deficit/hyperactivity disorder (ADHD), and obesity because the affected tissues express vitD receptors. Furthermore, obesity, AD, and BA are regarded as inflammatory diseases. Therefore, we hypothesized that vitD concentrations are lower in children with AD, BA, ADHD, and obesity compared to healthy children. We measured 25-hydroxyvitamin D concentrations in 235 children (60% boys, age 9.3±1.7years) with obesity, BA, AD, or ADHD and compared them to those of 3352 children from a healthy population. Additionally, parathyroid hormone was measured in the children with obesity, ADHD, BA, and AD. VitD concentrations were not lower in children with obesity, ADHD, BA, and AD compared to healthy children. In multiple regression analyses adjusted to migration background, time period of blood sample, age, and sex, VitD levels correlated significantly with the severity of AD measured by SCORing Atopic Dermatitis index and attention deficit measured by Conners questionnaire in ADHD. VitD levels were not linked to hyperactivity in ADHD, the severity of BA measured as forced expiration volume in the first second, or body mass index standard deviation score. Parathyroid hormone was not associated with the activity of any analyzed disease. In conclusion, most of our findings do not support the hypothesis that vitD is involved in the pathogenesis of these entities.
Published: 2018

40. Progression of coronary artery calcification is stronger in poorly than in well controlled diabetes: Results from the Heinz Nixdorf Recall Study

Author: A A Mahabadi, Karl-Heinz Jöckel, Thomas Budde, Susanne Moebus, Nils Lehmann, Dietrich Grönemeyer, Bernd Kowall, Andreas Stang, Rainer Seibel, and Raimund Erbel
Subjects: Male, endocrine system diseases, Computed Tomography Angiography, Endocrinology, Diabetes and Metabolism, Medizin, Coronary Artery Disease, Type 2 diabetes, 030204 cardiovascular system & hematology, Cohort Studies, 0302 clinical medicine, Endocrinology, Risk Factors, Germany, Prospective Studies, 030212 general & internal medicine, education.field_of_study, Middle Aged, Coronary Vessels, Coronary artery calcium, Diabetes control, Practice Guidelines as Topic, Disease Progression, cardiovascular system, Cardiology, population characteristics, Female, Cohort study, medicine.medical_specialty, Population, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, cardiovascular diseases, Vascular Calcification, education, Aged, Glycated Hemoglobin, business.industry, nutritional and metabolic diseases, Odds ratio, medicine.disease, Hypoglycemia, Diabetes Mellitus, Type 2, Hyperglycemia, Coronary artery calcification, business, Diabetic Angiopathies, Follow-Up Studies
Abstract: Aim To assess associations between HbA1c and progression of coronary artery calcification (CAC) in persons with and without diabetes. Methods In the Heinz Nixdorf Recall Study, a population-based cohort study in Germany (N=3453, aged 45–74years), CAC was assessed by electron-beam tomography at baseline and at 5-year follow-up. At baseline, participants were divided into five groups: poorly (HbA1c≥7.0%) and well (HbA1c 5 (factor by which CAC after 5-year follow-up is larger than baseline CAC), and categories of CAC change, respectively. Results Relative to group V, adjusted percentage increase of the geometric mean of PF 5 (95% CI) was: 69.1% (33.9%;113.6%), 15.4% (−5.6%;41.1%), −4.1% (−22.2%;18.2%), 4.2% (−5.4%;14.8%) for groups I–IV, respectively. The corresponding odds ratios for annual CAC increase ≥100 Agatston units (reference: Conclusions In known diabetes, CAC progression was stronger in poor diabetes control. For newly detected diabetes diagnosed by HbA1c ≥6.5%, associations with CAC progression were weak.
Published: 2017

41. Association of Coronary Artery Calcium Score vs Age With Cardiovascular Risk in Older Adults An Analysis of Pooled Population-Based Studies

Author: Yuichiro Yano, M. Arfan Ikram, Khurram Nasir, Udo Hoffmann, Anne B. Newman, Amir A. Mahabadi, Christopher J. O'Donnell, Raimund Erbel, Joseph M. Massaro, Donald M. Lloyd-Jones, Klodian Dhana, Oscar H. Franco, Ron Blankstein, Hongyan Ning, Karl-Heinz Jöckel, Nils Lehmann, Stefan Möhlenkamp, Ralph B. D'Agostino, Maryam Kavousi, Joao A.C. Lima, Lewis H. Kuller, Albert Hofman, Kiang Liu, Philip Greenland, Epidemiology, Neurology, and Radiology & Nuclear Medicine
Subjects: medicine.medical_specialty, education.field_of_study, Framingham Risk Score, Proportional hazards model, business.industry, Population, Medizin, 030204 cardiovascular system & hematology, medicine.disease, Coronary Calcium Score, 03 medical and health sciences, Rotterdam Study, 0302 clinical medicine, Framingham Heart Study, Internal medicine, medicine, Cardiology, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, education, business, Stroke, Cohort study, Original Investigation
Abstract: Importance Besides age, other discriminators of atherosclerotic cardiovascular disease (ASCVD) risk are needed in older adults. Objectives To examine the predictive ability of coronary artery calcium (CAC) score vs age for incident ASCVD and how risk prediction changes by adding CAC score and removing only age from prediction models. Design, Setting, and Participants We conducted an analysis of pooled US population-based studies, including the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study. Results were compared with 2 European cohorts, the Rotterdam Study and the Heinz Nixdorf Recall Study. Participants underwent CAC scoring between 1998 and 2006 using cardiac computed tomography. The participants included adults older than 60 years without known ASCVD at baseline. Exposures Coronary artery calcium scores. Main Outcomes and Measures Incident ASCVD events including coronary heart disease (CHD) and stroke. Results The study included 4778 participants from 3 US cohorts, with a mean age of 70.1 years; 2582 (54.0%) were women, and 2431 (50.9%) were nonwhite. Over 11 years of follow-up (44 152 person-years), 405 CHD and 228 stroke events occurred. Coronary artery calcium score (vs age) had a greater association with incident CHD (C statistic, 0.733 vs 0.690; C statistics difference, 0.043; 95% CI of difference, 0.009-0.075) and modestly improved prediction of incident stroke (C statistic, 0.695 vs 0.670; C statistics difference, 0.025; 95% CI of difference, −0.015 to 0.064). Adding CAC score to models including traditional cardiovascular risk factors, with only age being removed, provided improved discrimination for incident CHD (C statistic, 0.735 vs 0.703; C statistics difference, 0.032; 95% CI of difference, 0.002-0.062) but not for stroke. Coronary artery calcium score was more likely than age to provide higher category-free net reclassification improvement among participants who experienced an ASCVD event (0.390; 95% CI, 0.312-0.467 vs 0.08; 95% CI −0.001 to 0.181) and to result in more accurate reclassification of risk for ASCVD events among these individuals. The findings were similar in the 2 European cohorts (n = 4990). Conclusions and Relevance Coronary artery calcium may be an alternative marker besides age to better discriminate between lower and higher CHD risk in older adults. Whether CAC score can assist in guiding the decision to initiate statin treatment for primary prevention in older adults requires further investigation.
Published: 2017

42. Corrigendum to ‘Dynamic risk assessment based on positron emission tomography scanning in diffuse large B-cell lymphoma: Post-hoc analysis from the PETAL trial’ [Eur J Canc 124 (January 2020) 25–36]

Author: Maher Hanoun, Stefan P. Müller, Karl-Heinz Jöckel, Marcus Brinkmann, Ulrich Dührsen, Jan Rekowski, Andreas Hüttmann, Ronald Boellaard, and Christine Schmitz
Subjects: Cancer Research, Oncology, medicine.diagnostic_test, business.industry, Positron emission tomography, Post-hoc analysis, Medicine, Regret, business, Nuclear medicine, Risk assessment, medicine.disease, Diffuse large B-cell lymphoma
Abstract: The authors regret that they confused the colours of the time-to-progression curves in Figure 4C and Figure 4D. The correct Figure 4 appears below. [Figure presented] The authors would like to apologise for any inconvenience caused.
Published: 2020

43. Genome-wide association study of immunoglobulin light chain amyloidosis in three patient cohorts: comparison with myeloma

Author: H. Goldschmidt, Ute Hegenbart, Chiara Campo, Gareth J. Morgan, Kari Hemminki, Asta Försti, David W. Johnson, Richard S. Houlston, Jonathan S. Mitchell, Peter Hoffmann, Philip N. Hawkins, M. I. da Silva Filho, Anna Jauch, Karl-Heinz Jöckel, Stefanie Huhn, M. M. Nöthen, Iman Meziane, Giovanni Palladini, Paolo Milani, Jolanta Nickel, Stefano Landi, Niels Weinhold, Dorota Rowcieno, Ashutosh D. Wechalekar, Stefan Schönland, and Giampaolo Merlini
Subjects: Adult, Male, 0301 basic medicine, Cancer Research, Pathology, medicine.medical_specialty, Medizin, Single-nucleotide polymorphism, Genome-wide association study, Immunoglobulin light chain, Polymorphism, Single Nucleotide, Immunoglobulin Light-chain Amyloidosis, 03 medical and health sciences, AL amyloidosis, medicine, Humans, Cyclin D1, Genetic Predisposition to Disease, Multiple myeloma, Aged, Aged, 80 and over, business.industry, Amyloidosis, Hematology, Middle Aged, medicine.disease, 030104 developmental biology, Oncology, Female, Immunoglobulin Light Chains, Multiple Myeloma, business, Monoclonal gammopathy of undetermined significance, Genome-Wide Association Study
Abstract: Immunoglobulin light chain (AL) amyloidosis is characterized by tissue deposition of amyloid fibers derived from immunoglobulin light chain. AL amyloidosis and multiple myeloma (MM) originate from monoclonal gammopathy of undetermined significance. We wanted to characterize germline susceptibility to AL amyloidosis using a genome-wide association study (GWAS) on 1229 AL amyloidosis patients from Germany, UK and Italy, and 7526 healthy local controls. For comparison with MM, recent GWAS data on 3790 cases were used. For AL amyloidosis, single nucleotide polymorphisms (SNPs) at 10 loci showed evidence of an association at P
Published: 2016

44. HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype

Author: Xiuqing Guo, Caitlin O. Rourke, Vilmundur Gudnason, Udo Hoffmann, Hanna J. Barnes, Hagen Kälsch, Stéphanie Debette, Christopher J. Nicholson, Susanne Moebus, Sagar U. Nigwekar, Andreas C. Mauer, Shih-Jen Hwang, Emmanuel S. Buys, George Thanassoulis, Christopher J. O'Donnell, Haakon H. Sigurslid, Tamara B. Harris, Mary F. Feitosa, Matthew J. Budoff, Mark E. Lindsay, Michael H. Criqui, Barry I. Freedman, Jerome I. Rotter, Wendy S. Post, Sigurdur Sigurdsson, Andrew D. Johnson, Markus M. Nöthen, Ci Song, Quenna Wong, Judy Wang, Jie Yao, Aranya Bagchi, Nora Franceschini, Lingyi Lu, Mary D. Buswell, Daniel Bloch, Raimund Erbel, Florian Wunderer, Christian L. Lino Cardenas, Karl-Heinz Jöckel, Donald W. Bowden, Catherine Y. Campbell, Rajeev Malhotra, Sonali Pechlivanis, Xiaoling Zhang, Albert V. Smith, Georgia Shelton, Charles Slocum, Warren M. Zapol, David K. Rhee, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Pathology, Vascular smooth muscle, Medizin, Genome-wide association study, Inbred C57BL, Cardiovascular, Medical and Health Sciences, Muscle, Smooth, Vascular, Cohort Studies, Mice, 0302 clinical medicine, 2.1 Biological and endogenous factors, Aetiology, Aorta, Mice, Knockout, 0303 health sciences, Abdominal aorta, GTPase-Activating Proteins, Single Nucleotide, Middle Aged, Biological Sciences, Phenotype, 3. Good health, Heart Disease, cardiovascular system, Muscle, Female, Smooth, medicine.symptom, Muscle contraction, Muscle Contraction, medicine.medical_specialty, Knockout, Biology, Polymorphism, Single Nucleotide, Histone Deacetylases, Contractility, 03 medical and health sciences, Rare Diseases, medicine.artery, Vascular, medicine, Genetics, Animals, Humans, Genetic Predisposition to Disease, Polymorphism, Vascular Calcification, Heart Disease - Coronary Heart Disease, 030304 developmental biology, Aged, Prevention, HDAC9, Human Genome, medicine.disease, Atherosclerosis, Mice, Inbred C57BL, Repressor Proteins, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030217 neurology & neurosurgery, Calcification, Genome-Wide Association Study, Developmental Biology
Abstract: Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P
Published: 2019

45. Eight novel loci implicate shared genetic etiology in multiple myeloma, AL amyloidosis, and monoclonal gammopathy of unknown significance

Author: Miguel Inacio da Silva Filho, Markus M. Nöthen, Stefanie Huhn, Pavel Vodicka, Stefan Schönland, Göran Hallmans, Roman Hájek, Ludmila Vodickova, Giovanni Palladini, Kari Hemminki, Börge Schmidt, Paolo Milani, Ulrika Pettersson-Kymmer, Philip N. Hawkins, Per Hoffmann, Ashutosh D. Wechalekar, Hartmut Goldschmidt, Karl-Heinz Jöckel, Iman Meziane, Niels Weinhold, Stefano Landi, Hauke Thomsen, Ute Hegenbart, Claes Ohlsson, Richard S. Houlston, Dorota Rowcieno, Asta Försti, Subhayan Chattopadhyay, and Giampaolo Merlini
Subjects: 0301 basic medicine, Cancer Research, Monoclonal Gammopathy of Undetermined Significance, Polymorphism, Single Nucleotide, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Unknown Significance, Polymorphism (computer science), Genetic etiology, hemic and lymphatic diseases, medicine, AL amyloidosis, Biomarkers, Tumor, Humans, Immunoglobulin Light-chain Amyloidosis, Polymorphism, Multiple myeloma, Tumor, business.industry, Hematology, Single Nucleotide, medicine.disease, Prognosis, Monoclonal gammopathy, 030104 developmental biology, Oncology, Genetic Loci, 030220 oncology & carcinogenesis, Immunology, medicine.symptom, business, Multiple Myeloma, Genome-Wide Association Study, Biomarkers
Abstract: Eight novel loci implicate shared genetic etiology in multiple myeloma, AL amyloidosis, and monoclonal gammopathy of unknown significance
Published: 2019

46. Tobacco smoking and alcohol consumption as risk factors for thymoma - A European case-control study

Author: Pascal Guénel, Agustín Llopis González, Lorenzo Richiardi, Preben Johansen, Franco Merletti, Noemia Afonso, Altamiro Costa-Pereira, Mikael Eriksson, Wolfgang Ahrens, Linda Kaerlev, Svend Sabroe, Brigitte Trétarre, Karl-Heinz Jöckel, Gun Wingren, and María Morales Suárez-Varela
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Thymoma, Alcohol Drinking, Epidemiology, Colorectal cancer, Thymus cancer, Population, Medizin, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, education, Aged, Alcohol, Case-control study, Risk factors, Tobacco smoking, education.field_of_study, business.industry, Middle Aged, medicine.disease, Increased risk, Oncology, Case-Control Studies, 030220 oncology & carcinogenesis, Etiology, Female, business, Alcohol consumption
Abstract: PURPOSE: Hardly anything is known about the aetiology of thymoma. This paper presents data regarding tobacco smoking and alcohol consumption in relation to thymoma from the first case-control study performed on this rare tumour.METHODS: A European multi-centre case-control study including incident cases aged 35-69 years with thymoma between 1995 and 1997, was conducted in seven countries. A set of controls, used in seven parallel case-control studies by the same research group was used, including population-based controls from five countries and hospital controls with colon cancer from two countries. Altogether 103 cases, accepted by a reference pathologist, 712 colon cancer controls, and 2071 population controls were interviewed.RESULTS: Tobacco smoking was moderately related with thymoma (OR 1.4, 95% CI 0.9-2.2), and a tendency to dose-response was shown (p = 0.04), with an increased risk for heavy smokers defined as ≥41 pack-years (OR 2.1, 95% CI 1.1-3.9). A high consumption of spirits defined as ≥25 g of alcohol per day was associated with an increased risk of thymoma (OR 2.4, 95% CI 1.1-5.4), whereas no association was found with beer or wine.CONCLUSIONS: Tobacco smoking and a high intake of spirits were indicated as risk factors for thymoma.
Published: 2019

47. Publisher Correction: Mendelian randomisation study of the relationship between vitamin D and risk of glioma

Author: Ben Kinnersley, Rose Lai, Preetha Rajaraman, Karl-Heinz Jöckel, Markus M. Nöthen, Alex J. Cornish, Joellen M. Schildkraut, Quinn T. Ostrom, Dora Il'yasova, Richard S. Houlston, Matthias Simon, Margaret Wrensch, Georgina Armstrong, Karim Labreche, Christoffer Johansen, Hannah Takahashi, Robert B. Jenkins, Minouk J. Schoemaker, Elizabeth B. Claus, Clare Turnbull, Stephen J. Chanock, Amit Sud, Jeanette E. Eckel-Passow, Melissa L. Bondy, Jonine L. Bernstein, Beatrice Melin, Per Hoffmann, Philip J. Law, Jill S. Barnholtz-Sloan, Marc Sanson, and Sara H. Olson
Subjects: Medizin, lcsh:Medicine, Bioinformatics, Polymorphism, Single Nucleotide, symbols.namesake, Text mining, Glioma, medicine, Vitamin D and neurology, Humans, Genetic Predisposition to Disease, Vitamin D, lcsh:Science, Multidisciplinary, Brain Neoplasms, business.industry, lcsh:R, Genetic Variation, Mendelian Randomization Analysis, medicine.disease, Publisher Correction, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Mendelian inheritance, symbols, lcsh:Q, business
Abstract: To examine for a causal relationship between vitamin D and glioma risk we performed an analysis of genetic variants associated with serum 25-hydroxyvitamin D (25(OH)D) levels using Mendelian randomisation (MR), an approach unaffected by biases from confounding. Two-sample MR was undertaken using genome-wide association study data. Single nucleotide polymorphisms (SNPs) associated with 25(OH)D levels were used as instrumental variables (IVs). We calculated MR estimates for the odds ratio (OR) for 25(OH)D levels with glioma using SNP-glioma estimates from 12,488 cases and 18,169 controls, using inverse-variance weighted (IVW) and maximum likelihood estimation (MLE) methods. A non-significant association between 25(OH)D levels and glioma risk was shown using both the IVW (OR = 1.21, 95% confidence interval [CI] = 0.90-1.62, P = 0.201) and MLE (OR = 1.20, 95% CI = 0.98-1.48, P = 0.083) methods. In an exploratory analysis of tumour subtype, an inverse relationship between 25(OH)D levels and glioblastoma (GBM) risk was identified using the MLE method (OR = 0.62, 95% CI = 0.43-0.89, P = 0.010), but not the IVW method (OR = 0.62, 95% CI = 0.37-1.04, P = 0.070). No statistically significant association was shown between 25(OH)D levels and non-GBM glioma. Our results do not provide evidence for a causal relationship between 25(OH)D levels and all forms of glioma risk. More evidence is required to explore the relationship between 25(OH)D levels and risk of GBM.
Published: 2019

48. Exposure to welding fumes, hexavalent chromium, or nickel and risk of lung cancer

Author: Thomas Brüning, Benjamin Kendzia, Jack Siemiatycki, Heinz-Erich Wichmann, Beate Pesch, Wolfgang Zschiesche, Hermann Pohlabeln, Karl-Heinz Jöckel, Dirk Taeger, Thomas Behrens, and Wolfgang Ahrens
Subjects: Adult, Chromium, Male, medicine.medical_specialty, Lung Neoplasms, Epidemiology, Metals, Occupation, Smoking, Welders, Medizin, Cumulative Exposure, Welding, 010501 environmental sciences, 01 natural sciences, Gastroenterology, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Nickel, law, Germany, Internal medicine, medicine, Humans, 030212 general & internal medicine, Hexavalent chromium, Lung cancer, Aged, 0105 earth and related environmental sciences, Exposure assessment, business.industry, Case-control study, technology, industry, and agriculture, Odds ratio, Middle Aged, respiratory system, medicine.disease, Confidence interval, Occupational Diseases, chemistry, Case-Control Studies, business
Abstract: To investigate the risk of lung cancer after exposure to welding fumes, hexavalent chromium (Cr(VI)), and nickel, we analyzed 3,418 lung cancer cases and 3,488 controls among men from 2 German case-control studies (1988–1996). We developed a welding-process exposure matrix from measurements of these agents, and this was linked with welding histories from a job-specific questionnaire to calculate cumulative exposure variables. Logistic regression models were fitted to estimate odds ratios with confidence intervals conditional on study, and they adjusted for age, smoking, and working in other at-risk occupations. Additionally, we mutually adjusted for the other exposure variables under study. Overall, 800 cases and 645 controls ever worked as regular or occasional welders. Odds ratios for lung cancer with high exposure were 1.55 (95% confidence interval (CI): 1.17, 2.05; median, 1.8 mg/m3 × years) for welding fumes, 1.85 (95% CI: 1.35, 2.54; median, 1.4 μg/m3 × years) for Cr(VI), and 1.60 (95% CI: 1.21, 2.12; median, 9 μg/m3 × years) for nickel. Risk estimates increased with increasing cumulative exposure to welding fumes and with increasing exposure duration for Cr(VI) and nickel. Our results showed that welding fumes, Cr(VI), and nickel might contribute independently to the excess lung cancer risk associated with welding. However, quantitative exposure assessment remains challenging.
Published: 2019

49. Six versus eight doses of rituximab in patients with aggressive B cell lymphoma receiving six cycles of CHOP : results from the 'Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas' (PETAL) trial

Author: Bernd Hertenstein, Lars Kurch, Roland Schroers, Andreas Hüttmann, Thomas Krohn, Georg Maschmeyer, Ariane Dienst, Heinz-Gert Höffkes, Ingo Brink, Gabriele Prange-Krex, Aruna Raghavachar, Alfred Klein, Christine Schmitz, Andreas Schwarzer, Gabriele Pöpperl, Wolfram Klapper, Andreas Hertel, Martin Griesshammer, Stefan P. Müller, Matthias Weckesser, Ralph Naumann, Heike Steiniger, Matthias Grube, Wolfgang Römer, Dieter Hoelzer, Marcus Brinkmann, Jan Dürig, Christiane Franzius, Thomas Südhoff, Frank M. Bengel, Holger Nückel, Claudia Ose, Ulrich Dührsen, Karl-Heinz Jöckel, Jan Rekowski, Thomas Höhler, Aristoteles Giagounidis, Arnold Ganser, Dennis Hahn, Paul La Rosée, Helga Bernhard, Jörg Kotzerke, Frank Kroschinsky, Hubertus Hautzel, Dirk Behringer, Jochen Schütte, Tobias Gaska, Rolf M. Mesters, Ferras Alashkar, Jens Holzinger, Stefan Wilop, Jörg Marienhagen, and Martin Freesmeyer
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Lymphoma, B-Cell, Adolescent, Follicular lymphoma, Medizin, CHOP, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, International Prognostic Index, Fluorodeoxyglucose F18, immune system diseases, hemic and lymphatic diseases, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, B-cell lymphoma, Cyclophosphamide, Aged, Aged, 80 and over, business.industry, Hematology, General Medicine, Middle Aged, medicine.disease, Lymphoma, Survival Rate, Doxorubicin, Vincristine, Positron-Emission Tomography, 030220 oncology & carcinogenesis, Prednisone, Female, Rituximab, Primary mediastinal B-cell lymphoma, business, Diffuse large B-cell lymphoma, Follow-Up Studies, 030215 immunology, medicine.drug
Abstract: Standard first-line treatment of aggressive B cell lymphoma comprises six or eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus eight doses of rituximab (R). Whether adding two doses of rituximab to six cycles of R-CHOP is of therapeutic benefit has not been systematically investigated. The Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas (PETAL) trial investigated the ability of [18F]-fluorodesoxyglucose PET scanning to guide treatment in aggressive non-Hodgkin lymphomas. Patients with B cell lymphomas and a negative interim scan received six cycles of R-CHOP with or without two extra doses of rituximab. For reasons related to trial design, only about a third underwent randomization between the two options. Combining randomized and non-randomized patients enabled subgroup analyses for diffuse large B cell lymphoma (DLBCL; n = 544), primary mediastinal B cell lymphoma (PMBCL; n = 37), and follicular lymphoma (FL) grade 3 (n = 35). With a median follow-up of 52 months, increasing the number of rituximab administrations failed to improve outcome. A non-significant trend for improved event-free survival was seen in DLBCL high-risk patients, as defined by the International Prognostic Index, while inferior survival was observed in female patients below the age of 60 years. Long-term outcome in PMBCL was excellent. Differences between FL grade 3a and FL grade 3b were not apparent. The results were confirmed in a Cox proportional hazard regression model and a propensity score matching analysis. In conclusion, adding two doses of rituximab to six cycles of R-CHOP did not improve outcome in patients with aggressive B cell lymphomas and a fast metabolic treatment response.
Published: 2019

50. Herpes zoster incidence in Germany - an indirect validation study for self-reported disease data from pretest studies of the population-based German National Cohort

Author: Mahrrouz Caputo, Thomas Keil, Stefanie Castell, Susanne Moebus, Barbara Hoffmann, Claudia Sievers, Michael F. Leitzmann, Christa Meisinger, André Karch, Sabine Schipf, Bettina Braun, Heiko Becher, Birgit Klüppelholz, Börge Schmidt, Wolfgang Lieb, Johannes Horn, Nadia Obi, Hermann Brenner, Manas K. Akmatov, Tobias Pischon, Karl-Heinz Jöckel, Lilian Krist, Astrid Steinbrecher, Jakob Linseisen, Kathrin Günther, Rafael T. Mikolajczyk, Beate Fischer, Henry Völzke, and Guido Giani
Subjects: Male, 0301 basic medicine, Herpesvirus 3, Human, Herpes zoster, Medizin, Neuralgia, Postherpetic, Disease, Postherpetic neuralgia, Validity, German National Cohort, Self-reports, Incidence, Cohort Studies, German, 610 Medical sciences Medicine, 0302 clinical medicine, Germany, Surveys and Questionnaires, Recall bias, 030212 general & internal medicine, Incidence (epidemiology), Age Factors, Middle Aged, Infectious Diseases, language, Female, Research Article, Adult, Validation study, 030106 microbiology, National cohort, lcsh:Infectious and parasitic diseases, Young Adult, 03 medical and health sciences, Sex Factors, medicine, Humans, lcsh:RC109-216, ddc:610, Disease burden, Aged, business.industry, Herpes Zoster, Postherpetic Neuralgia, Reproducibility of Results, medicine.disease, language.human_language, Cardiovascular and Metabolic Diseases, Self Report, business, Demography
Abstract: Background Until now, herpes zoster (HZ)-related disease burden in Germany has been estimated based on health insurance data and clinical findings. However, the validity of self-reported HZ is unclear. This study investigated the validity of self-reported herpes zoster (HZ) and its complication postherpetic neuralgia (PHN) using data from the pretest studies of the German National Cohort (GNC) in comparison with estimates based on health insurance data. Methods Data of 4751 participants aged between 20 and 69 years from two pretest studies of the GNC carried out in 2011 and 2012 were used. Based on self-reports of physician-diagnosed HZ and PHN, age- and sex-specific HZ incidence rates and PHN proportions were estimated. For comparison, estimates based on statutory health insurance data from the German population were considered. Results Eleven percent (95%-CI, 10.4 to 12.3, n = 539) of the participants reported at least one HZ episode in their lifetime. Our estimated age-specific HZ incidence rates were lower than previous estimates based on statutory health insurance data. The PHN proportion in participants older than 50 years was 5.9% (1.9 to 13.9%), which was in line with estimates based on health insurance data. Conclusion As age- and sex-specific patterns were comparable with that in health insurance data, self-reported diagnosis of HZ seems to be a valid instrument for overall disease trends. Possible reasons for observed differences in incidence rates are recall bias in self-reported data or overestimation in health insurance data. Electronic supplementary material The online version of this article (10.1186/s12879-019-3691-2) contains supplementary material, which is available to authorized users.
Published: 2019

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