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Xue-Jiao Yang School of Public Health, Medical College of Soochow University, Suzhou, China

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Le-Yang Zhang Medical College of Soochow University, Suzhou, China

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Qing-Hua Ma The 3rd People’s Hospital of Xiangcheng District, Suzhou, China

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Hong-Peng Sun School of Public Health, Medical College of Soochow University, Suzhou, China

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Yong Xu School of Public Health, Medical College of Soochow University, Suzhou, China

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Xing Chen Department of Children Health Care, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China

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Chen-Wei Pan School of Public Health, Medical College of Soochow University, Suzhou, China

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Purpose:

We aimed to examine the associations of platelet parameters with the presence of metabolic syndrome in community-dwelling older Chinese adults.

Methods:

Study sample was from the Weitang Geriatric Diseases Study, which included 4338 individuals aged 60 years or above. The mean age of the participants was 68 years. Metabolic syndrome was defined based on the Adult Treatment Panel III criteria. Platelet parameters were assessed using an automated hematology analyzer. Multiple logistic regression models were fitted to examine relationships between the platelet parameters and the presence of metabolic syndrome after adjusting for potential confounders.

Results:

The adjusted odds ratio (95% CI) of metabolic syndrome for the highest quartile of platelet parameters (platelet count, mean platelet volume, plateletcrit, platelet distribution width, platelet larger cell ratio) when compared to the lowest quartile were 1.32 (1.06, 1.64), 1.00 (0.81, 1.24), 1.37 (1.10, 1.71), 1.45 (1.14, 1.83), 1.11 (0.89, 1.39), respectively. Hypertension and diabetes modified the relationship between platelet distribution width and metabolic syndrome with the associations being significant in hypertensive and non-diabetic groups. The levels of platelet distribution width increased with the risk of metabolic syndrome in men but not in women.

Conclusion:

The levels of platelet count, plateletcrit and platelet distribution width increased in older adults with metabolic syndrome, suggesting that these parameters may be useful biomarkers for further risk appraisal of metabolic syndrome in aged population.

Open access
Hsiao-Yun Yeh Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

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Hung-Ta Hondar Wu Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Division of Musculoskeletal Section, Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan

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Hsiao-Chin Shen Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan

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Tzu-Hao Li Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Foundation, Taipei, Taiwan
School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan

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Ying-Ying Yang Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

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Kuei-Chuan Lee Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

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Yi-Hsuan Lin Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

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Chia-Chang Huang Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan

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Ming-Chih Hou Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

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Objective

Previous studies have suggested that body mass index (BMI) should be considered when assessing the relationship between fatty liver (FL) and osteoporosis. The aim of this study was to investigate future fracture events in people with FL, focusing on the effect of BMI in both sexes.

Methods

This retrospective cohort study, spanning from 2011 to 2019, enrolled 941 people, including 441 women and 500 men, aged 50 years or older who underwent liver imaging (ultrasound, computed tomography, or magnetic resonance image) and dual-energy X-ray absorptiometry (for bone mineral density measurements). The study examined predictors of osteoporosis in both sexes and the effect of different ranges of BMI (18.5–24, 24–27, and ≥27 kg/m2) on the risk of future fracture events in FL patients.

Results

The average follow-up period was 5.3 years for women and 4.2 years for men. Multivariate analysis identified age and BMI as independent risk factors of osteoporosis in both sexes. Each unit increase in BMI decreased the risk of osteoporosis by ≥10%. In both women and men with FL, a BMI of 24–27 kg/m2 offered protection against future fractures, compared to those without FL and with a BMI of 18.5–24 kg/m2.

Conclusion

The protective effect of a higher BMI against future fractures in middle-aged and elderly female and male patients with FL is not uniform and diminishes beyond certain BMI ranges.

Open access
Marie Auzanneau Institute of Epidemiology and Medical Biometry, ZIBMT, Medical Faculty of Ulm University, Ulm, Germany
German Center for Diabetes Research (DZD), Neuherberg, Germany

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Alexander J Eckert Institute of Epidemiology and Medical Biometry, ZIBMT, Medical Faculty of Ulm University, Ulm, Germany
German Center for Diabetes Research (DZD), Neuherberg, Germany

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Andreas Fritsche German Center for Diabetes Research (DZD), Neuherberg, Germany
Department of Internal Medicine IV, University Hospital Tübingen, Germany
Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany

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Martin Heni Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
Division of Endocrinology and Diabetology, Department of Internal Medicine 1, University Hospital Ulm, Ulm, Germany
Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen, Germany

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Andrea Icks German Center for Diabetes Research (DZD), Neuherberg, Germany
Institute of Health Services Research and Health Economics, Center for Health and Society, Faculty of Medicine, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Institute of Health Services Research and Health Economics, German Diabetes Center (DDZ), Leibniz Centre for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

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Annabel S Mueller-Stierlin Department of General Practice and Primary Care, University Hospital Ulm, Um, Germany
Department of Psychiatry and Psychotherapy II, University Hospital Ulm, Um, Germany

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Ana Dugic Department of Gastroenterology, Klinikum Bayreuth, Medizincampus Oberfranken der Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Bayreuth, Germany

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Alexander Risse Diabetes Center at Sophie-Charlotte-Platz, Diabetes Foot Unit, Berlin, Germany

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Stefanie Lanzinger Institute of Epidemiology and Medical Biometry, ZIBMT, Medical Faculty of Ulm University, Ulm, Germany
German Center for Diabetes Research (DZD), Neuherberg, Germany

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Reinhard W Holl Institute of Epidemiology and Medical Biometry, ZIBMT, Medical Faculty of Ulm University, Ulm, Germany
German Center for Diabetes Research (DZD), Neuherberg, Germany

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Objective

To analyze the proportion of diabetes among all hospitalized cases in Germany between 2015 and 2020.

Methods

Using the nationwide Diagnosis-Related-Groups statistics, we identified among all inpatient cases aged ≥ 20 years all types of diabetes in the main or secondary diagnoses based on ICD-10 codes, as well all COVID-19 diagnoses for 2020.

Results

From 2015 to 2019, the proportion of cases with diabetes among all hospitalizations increased from 18.3% (3.01 of 16.45 million) to 18.5% (3.07 of 16.64 million). Although the total number of hospitalizations decreased in 2020, the proportion of cases with diabetes increased to 18.8% (2.73 of 14.50 million). The proportion of COVID-19 diagnosis was higher in cases with diabetes than in those without in all sex and age subgroups. The relative risk (RR) for a COVID-19 diagnosis in cases with vs without diabetes was highest in age group 40–49 years (RR in females: 1.51; in males: 1.41).

Conclusions

The prevalence of diabetes in the hospital is twice as high as the prevalence in the general population and has increased further with the COVID-19 pandemic, underscoring the increased morbidity in this high-risk patient group. This study provides essential information that should help to better estimate the need for diabetological expertise in inpatient care settings.

Open access
Charissa van Zwol-Janssens Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Aglaia Hage Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Kim van der Ham Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Birgitta K Velthuis Department of Radiology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands

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Ricardo P J Budde Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands

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Maria P H Koster Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Arie Franx Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Bart C J M Fauser Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht & University of Utrecht, Utrecht, the Netherlands

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Eric Boersma Department of Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Daniel Bos Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Joop S E Laven Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Yvonne V Louwers Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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the CREW consortium
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the CREW consortium

Besides age, estrogen exposure plays a crucial role in changes in bone density (BD) in women. Premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS) are conditions in reproductive-aged women in which the exposure to estrogen is substantially different. Women with a history of preeclampsia (PE) are expected to have normal estrogen exposure. Within the CREw-IMAGO study, we investigated if trabecular BD is different in these women because of differences in the duration of estrogen exposure. Trabecular BD was measured in thoracic vertebrae on coronary CT scans. Women with a reduced estrogen exposure (POI) have a lower BD compared to women with an intermediate exposure (PE) (mean difference (MD) −26.8, 95% CI −37.2 to −16.3). Women with a prolonged estrogen exposure (PCOS) have the highest BD (MD 15.0, 95% CI 4.3–25.7). These results support the hypothesis that the duration of estrogen exposure in these women is associated with trabecular BD.

Significance statement

Our results suggest that middle-aged women with PCOS have a higher BD and women with POI have a lower BD. We hypothesized that this is due to either a prolonged estrogen exposure, as seen in women with PCOS, or a reduced estrogen exposure, as in women with POI. In the counseling of women with reproductive disorders on long-term health issues, coronary CT provides a unique opportunity to assess both coronary artery calcium score for cardiovascular screening as well as trabecular BD.

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R H M Dykgraaf Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

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S Schalekamp-Timmermans Division of Obstetrics and Fetal Medicine, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

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M C Adank Division of Obstetrics and Fetal Medicine, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

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S A A van den Berg Department of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

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B M N van de Lang-Born Department of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

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T I M Korevaar Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

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A Kumar Ansh Labs, Webster, Texas, USA

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B Kalra Ansh Labs, Webster, Texas, USA

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G V Savjani Ansh Labs, Webster, Texas, USA

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E A P Steegers Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
Division of Obstetrics and Fetal Medicine, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

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Y V Louwers Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

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J S E Laven Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

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Objective

The primary objective of this study is to establish maternal reference values of anti‐Müllerian hormone (AMH) in a fertile multi-ethnic urban pregnant population and to evaluate the effect of gestational age. The secondary objective of this study is to explore the association between AMH and placental biomarkers.

Design

This study was embedded in the Generation R Study, an ongoing population-based prospective cohort study from early pregnancy onwards.

Setting

City of Rotterdam, the Netherlands, out of hospital setting.

Patients

In 5806 women, serum AMH levels were determined in early pregnancy (median 13.5 weeks; 95% range 10.5–17.2).

Intervention(s)

None.

Main outcome measures

Maternal AMH levels in early pregnancy and its association with placental biomarkers, including human chorionic gonadotrophin (hCG), soluble fms-like tyrosine kinase-1 (sFLT), and placental growth factor (PLGF).

Results

A nomogram of AMH in early pregnancy was developed. Serum AMH levels showed a decline with advancing gestational age. Higher AMH levels were associated with a higher level of the placental biomarkers hCG and sFLT in early pregnancy. This last association was predominantly mediated by hCG. AMH levels were negatively associated with PLGF levels.

Conclusion

In this large study, we show that AMH levels in early pregnancy decrease with advancing gestational age. The association between AMH and the placental biomarkers hCG, sFLT, and PLGF suggests a better placental development with lower vascular resistance in mothers with higher AMH levels. Hence, AMH might be useful in predicting adverse pregnancy outcomes due to impaired placental development.

Open access
Xu-Feng Chen Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

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Cong He Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

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Peng-Cheng Yu Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

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Wei-Dong Ye Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

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Pei-Zheng Han Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

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Jia-Qian Hu Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

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Yu-Long Wang Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

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Next-generation sequencing (NGS) is of great benefit to clinical practice in terms of identifying genetic alterations. This study aims to clarify the gene background and its influence on thyroid tumors in the Chinese population. NGS data and corresponding clinicopathological features (sex, age, tumor size, extrathyroidal invasion, metastasis, multifocality, and TNM stage) were collected and analyzed retrospectively from 2844 individual thyroid tumor samples from July 2021 to August 2022. Among the cohort, 2337 (82%) cases possess genetic alterations, including BRAF (71%), RAS (4%), RET/PTC (4%), TERT (3%), RET (2.2%), and TP53 (1.4%). Diagnostic sensitivity before surgery can be significantly increased from 0.76 to 0.91 when cytology is supplemented by NGS. Our results show that BRAF-positive papillary thyroid cancer (PTC) patients tend to have older age, smaller tumor size, less vascular invasion, more frequent tumor multifocality, and a significantly higher cervical lymph node metastatic rate. Mutation at RET gene codons 918 and 634 is strongly correlated with medullary thyroid cancer. However, it did not display more invasive clinical characteristics. TERT-positive patients are more likely to have older age, and have larger tumor size, more tumor invasiveness, and more advanced TNM stage, indicating a poor prognosis. Patients with TERT, RET/PTC1, and CHEK2 mutations are more susceptible to lateral lymph node metastasis. In conclusion, NGS can be a useful tool that provides practical gene evidence in the process of diagnosis and treatment in thyroid tumors.

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Clara Lundetoft Clausen Center of Research & Disruption of Infectious Diseases, Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark

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Åse Krogh Rasmussen Department of Medical Endocrinology and Metabolism, Copenhagen University Hospital, Copenhagen, Denmark

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Trine Holm Johannsen Department of Growth and Reproduction, Copenhagen University Hospital, Copenhagen, Denmark

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Linda Maria Hilsted Department of Clinical Biochemistry, Copenhagen University Hospital, Copenhagen, Denmark

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Niels Erik Skakkebæk Department of Growth and Reproduction, Copenhagen University Hospital, Copenhagen, Denmark

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Pal Bela Szecsi Department of Clinical Biochemistry, Holbæk Hospital, Holbæk, Denmark

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Lise Pedersen Department of Clinical Biochemistry, Holbæk Hospital, Holbæk, Denmark

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Thomas Benfield Center of Research & Disruption of Infectious Diseases, Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Anders Juul Department of Growth and Reproduction, Copenhagen University Hospital, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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The hypothalamic–pituitary–thyroid hormone axis might be affected in COVID-19, but existing studies have shown varying results. It has been hypothesized that hyperinflammation, as reflected by the secretion of cytokines, might induce thyroid dysfunction among patients with COVID-19. We explored thyroid hormone involvement in the acute phase of symptomatic COVID-19 and its possible associations with cytokine levels and mortality risk. This was a single-center study of 116 consecutive patients hospitalized for moderate-to-severe COVID-19 disease. Serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine (T4), and 45 cytokines/chemokines were measured in all patients within 3 days of admission. Data were extracted retrospectively through a manual review of health records. At admission, 95 (81.9%) were euthyroid; while 21 (18.1%) had biochemically thyroid dysfunction including subclinical thyrotoxicosis (n = 11), overt thyrotoxicosis (n = 2), hypothyroidism (n = 1), non-thyroidal illness (n = 2), and normal TSH but high free T4 (n = 5). TSH levels were inversely correlated with IL-8 (r s = –0.248), IL-10 (r s = –0.253), IL-15 (r s = –0.213), IP-10 (r s = –0.334), and GM-CSF (r s = –0.254). Moreover, IL-8 levels, IP-10, and GM-CSF were significantly higher in patients with serum TSH < 0.4 mIU/L. Lastly, a two-fold increment of IL-8 and IL-10 was associated with significantly higher odds of having TSH < 0.4 mIU/L (odds ratio 1.86 (1.11–3.10) and 1.78 (1.03–3.06)). Serum TSH was not associated with 30- or 90-day mortality. In conclusion, this study suggests that fluctuations of TSH levels in patients with COVID-19 may be influenced by circulating IL-8, IL-10, IL-15, IP-10, and GM-CSF as previously described in autoimmune thyroid diseases.

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Emmi Naskali Department of Dermatology, Allergology and Venereology, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland

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Katja Dettmer Institute of Functional Genomics, University of Regensburg, Regensburg, Germany

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Peter J Oefner Institute of Functional Genomics, University of Regensburg, Regensburg, Germany

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Pedro A B Pereira Institute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, Helsinki, Finland

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Kai Krohn Clinical Research Institute HUCH Ltd, Biomedicum Helsinki 1, Helsinki, Finland

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Petri Auvinen Institute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, Helsinki, Finland

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Annamari Ranki Department of Dermatology, Allergology and Venereology, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland

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Nicolas Kluger Department of Dermatology, Allergology and Venereology, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland

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Objective

Intestinal autoimmunity with gastrointestinal (GI) dysfunction has been shown in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Patients lack entero-endocrine (EE) cells and have circulating autoantibodies (Aabs) against critical enzymes in serotonin (5-HT) biosynthesis.

Design

We sought to determine the serum levels of 5-HT, tryptophan (Trp) metabolites and L-DOPA in 37 Finnish APECED patients and to correlate their abundance with the presence of TPH and AADC Aabs, GI dysfunction and depressive symptoms. We also performed an exploratory analysis of the gut microbiome.

Methods

Serum 5-HT, L-DOPA and Trp metabolite levels were determined by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). TPH and AADC Aabs were measured by ELISA. Depression was assessed with a structured RBDI questionnaire. The V3–V4 regions of the bacterial 16S rRNA gene were sequenced for gut microbiome exploration.

Results

Serum 5-HT levels were significantly decreased (130 ± 131 nmol/L vs 686 ± 233 nmol/L, P < 0.0001) in APECED patients with TPH-1 (±AADC) Aabs compared to controls and patients with only AADC Aabs. Reduced 5-HT levels correlated with constipation. The genus Escherichia/Shigella was overrepresented in the intestinal microbiome. No correlation between serum Trp, 5-HT or l-DOPA levels and the RBDI total score, fatigue or sleep disorders was found.

Conclusions

This exploratory study found low serum levels of 5-HT to be associated with constipation and the presence of TPH-1 and AADC Aabs, but not with symptoms of depression. Hence, serum 5-HT, TPH1 and AADC Aabs should be determined in APECED patients presenting with GI symptoms.

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Yun Hu Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Jiangsu, China
Department of Immunology, Nanjing Medical University, Jiangsu, China

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Na Li Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Jiangsu, China

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Peng Jiang Department of Thyroid and Breast Surgery, Nanjing First Hospital, Nanjing Medical University, Jiangsu, China

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Liang Cheng Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Jiangsu, China

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Bo Ding Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Jiangsu, China

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Xiao-Mei Liu Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Jiangsu, China

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Ke He Department of Endocrinology, Wuxi Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangsu, China

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Yun-Qing Zhu Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Jiangsu, China

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Bing-li Liu Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Jiangsu, China

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Xin Cao Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Jiangsu, China

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Hong Zhou Department of Immunology, Nanjing Medical University, Jiangsu, China

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Xiao-Ming Mao Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Jiangsu, China

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Objective

Thyroid nodules are usually accompanied by elevated thyroglobulin (Tg) level and autoimmune thyroid diseases (AITDs). However, the relationship between Tg and AITDs is not fully understood. Dysfunction of regulatory T cells (Tregs) plays an important role in the development of AITDs. We aimed to evaluate the effects of Tg on the function of Tregs in patients with thyroid nodules.

Methods

Tg levels and the functions of Tregs in peripheral blood and thyroid tissues of patients with thyroid nodules from Nanjing First Hospital were evaluated. The effects of Tg on the function of Tregs from healthy donors were also assessed in vitro. The function of Tregs was defined as an inhibitory effect of Tregs on the effector T cell (CD4+ CD25 T cell) proliferation rate.

Results

The level of Tg in peripheral blood correlated negatively with the inhibitory function of Tregs (R = 0.398, P = 0.03), and Tregs function declined significantly in the high Tg group (Tg >77 μg/L) compared with the normal Tg group (11.4 ± 3.9% vs 27.5 ± 3.5%, P < 0.05). Compared with peripheral blood, the function of Tregs in thyroid declined significantly (P < 0.01), but the proportion of FOXP3+ Tregs in thyroid increased (P < 0.01). High concentration of Tg (100 μg/mL) inhibited the function of Tregs and downregulated FOXP3, TGF-β and IL-10 mRNA expression in Tregs in vitro.

Conclusions

Elevated Tg level could impair the function of Tregs, which might increase the risk of AITDs in patient with thyroid nodules.

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Yongping Liu Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, People’s Republic of China

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Shuo Wang Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, People’s Republic of China

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Qingling Guo Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, People’s Republic of China

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Yongze Li Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, People’s Republic of China

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Jing Qin Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, People’s Republic of China

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Na Zhao Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, People’s Republic of China

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Yushu Li Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, People’s Republic of China

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Zhongyan Shan Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, People’s Republic of China

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Weiping Teng Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, People’s Republic of China

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Objective

Hashimoto’s thyroiditis (HT) is characterized by elevated specific auto-antibodies, including TgAb and TPOAb. Increasing evidence has demonstrated the essential role of Th17 cells in HT. However, the underlying mechanism is still unclear. Semaphorin 5A (Sema 5A) is involved in several autoimmune diseases through the regulation of immune cells. The aim of the present study was to explore the role of Sema 5A in HT.

Methods

We measured serum Sema 5A levels in HT (n = 92) and healthy controls (n = 111) by enzyme-linked immunosorbent assay (ELISA). RNA levels of Sema 5A and their receptors (plexin-A1 and plexin-B3), as well as several cytokines (IFN-γ, IL-4 and IL-17), were detected by real-time polymerase chain reaction in peripheral blood mononuclear cells from 23 patients with HT and 31 controls. In addition, we investigated the relationship between serum Sema 5A and HT.

Results

Serum Sema 5A in HT increased significantly compared with healthy controls (P < 0.001). Moreover, serum Sema 5A levels were positively correlated with TgAb (r = 0.511, P < 0.001), TPOAb (r = 0.423, P < 0.001), TSH (r = 0.349, P < 0.001) and IL-17 mRNA expression (r = 0.442, P < 0.001). Increased Sema 5A RNA expression was observed (P = 0.041) in HT compared with controls. In receiver-operating characteristic (ROC) analysis, serum Sema 5A predicted HT with a sensitivity of 79.35% and specificity of 96.40%, and the area under the curve of the ROC curve was 0.836 (95% CI: 0.778–0.884, P < 0.001).

Conclusions

These data demonstrated elevated serum Sema 5A in HT patients for the first time. Serum Sema 5A levels were correlated with thyroid auto-antibodies and IL-17 mRNA expression. Sema 5A may be involved in immune response of HT patients.

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