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1. Increased Intrathecal Immune Activation in Virally Suppressed HIV-1 Infected Patients with Neurocognitive Impairment

Author: Edén, Arvid, Marcotte, Thomas D, Heaton, Robert K, Nilsson, Staffan, Zetterberg, Henrik, Fuchs, Dietmar, Franklin, Donald, Price, Richard W, Grant, Igor, Letendre, Scott L, and Gisslén, Magnus
Subjects: Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Neurodegenerative, Brain Disorders, Mental Health, HIV/AIDS, Neurosciences, Infectious Diseases, Clinical Research, Acquired Cognitive Impairment, Sexually Transmitted Infections, 2.1 Biological and endogenous factors, AIDS Dementia Complex, Adult, Anti-Retroviral Agents, Biomarkers, Female, HIV-1, Humans, Longitudinal Studies, Male, Middle Aged, Neopterin, Neurofilament Proteins, General Science & Technology
Abstract: ObjectiveAlthough milder forms of HIV-associated neurocognitive disorder (HAND) remain prevalent, a correlation to neuronal injury has not been established in patients on antiretroviral therapy (ART). We examined the relationship between mild HAND and CSF neurofilament light protein (NFL), a biomarker of neuronal injury; and CSF neopterin, a biomarker of CNS immunoactivation, in virally suppressed patients on antiretroviral therapy (ART).Design and methodsWe selected 99 subjects on suppressive ART followed longitudinally from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Based on standardized comprehensive neurocognitive performance (NP) testing, subjects were classified as neurocognitively normal (NCN; n = 29) or impaired (NCI; n = 70). The NCI group included subjects with asymptomatic (ANI; n = 37) or mild (MND; n = 33) HAND. CSF biomarkers were analyzed on two occasions.ResultsGeometric mean CSF neopterin was 25% higher in the NCI group (p = 0.04) and NFL and neopterin were significantly correlated within the NCI group (r = 0.30; p
Published: 2016

2. Long-term outcomes of patients with acromegaly: a report from the Swedish Pituitary Register

Author: Steinunn Arnardóttir, Jacob Järås, Pia Burman, Katarina Berinder, Per Dahlqvist, Eva Marie Erfurth, Charlotte Höybye, Karin Larsson, Oskar Ragnarsson, Bertil Ekman, and Britt Edén Engström
Subjects: Adenoma, Adult, Male, Antineoplastic Agents, Hormonal, Endocrinology, Diabetes and Metabolism, Vision Disorders, Radiosurgery, Hypopituitarism, Neurosurgical Procedures, Endocrinology, Cause of Death, Humans, Registries, Insulin-Like Growth Factor I, Mortality, Aged, Proportional Hazards Models, Sweden, Radiotherapy, General Medicine, Middle Aged, Tumor Burden, Chemotherapy, Adjuvant, Acromegaly, Linear Models, Female, Radiotherapy, Adjuvant, Growth Hormone-Secreting Pituitary Adenoma, Visual Fields, Somatostatin
Abstract: Objective To describe the treatment and long-term outcomes of patients with acromegaly from all healthcare regions in Sweden. Design and methods Analysis of prospectively reported data from the Swedish Pituitary Register of 698 patients (51% females) with acromegaly diagnosed from 1991 to 2011. The latest clinical follow-up date was December 2012, while mortality data were collected for 28.5 years until June 2019. Results The annual incidence was 3.7/million; 71% of patients had a macroadenoma, 18% had visual field defects, and 25% had at least one pituitary hormone deficiency. Eighty-two percent had pituitary surgery, 10% radiotherapy, and 39% medical treatment. At the 5- and 10-year follow-ups, insulin-like growth factor 1 levels were within the reference range in 69 and 78% of patients, respectively. In linear regression, the proportion of patients with biochemical control including adjuvant therapy at 10 years follow-up increased over time by 1.23% per year. The standardized mortality ratio (SMR) (95% CI) for all patients was 1.29 (1.11–1.49). For patients with biochemical control at the latest follow-up, SMR was not increased, neither among patients diagnosed between 1991 and 2000, SMR: 1.06 (0.85–1.33) nor between 2001 and2011, SMR: 0.87 (0.61–1.24). In contrast, non-controlled patients at the latest follow-up from both decades had elevated SMR, 1.90 (1.33–2.72) and 1.98 (1.24–3.14), respectively. Conclusions The proportion of patients with biochemical control increased over time. Patients with biochemically controlled acromegaly have normal life expectancy, while non-controlled patients still have increased mortality. The high rate of macroadenomas and unchanged age at diagnosis illustrates the need for improvements in the management of patients with acromegaly.
Published: 2022
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3. Inflammatory and metabolic markers in relation to outcome of in vitro fertilization in a cohort of predominantly overweight and obese women

Author: Henrik, Svensson, Snorri, Einarsson, Daniel, Olausson, Linda, Kluge, Christina, Bergh, Staffan, Edén, Malin, Lönn, and Ann, Thurin-Kjellberg
Subjects: Leptin, C-Reactive Protein, Multidisciplinary, Pregnancy Rate, Pregnancy, Humans, Female, Fertilization in Vitro, Obesity, Overweight, Birth Rate, Live Birth
Abstract: For overweight and obese women undergoing in vitro fertilization (IVF) the pregnancy and live birth rates are compromised while the underlying mechanisms and predictors are unclear. The aim was to explore the association between adipose tissue-related inflammatory and metabolic markers and the pregnancy and live birth outcome of IVF in a cohort of predominantly overweight and obese women. Serum samples, fulfilling standardizing criteria, were identified from 195 women having participated in either the control (n = 131) or intervention (n = 64) group of a randomized controlled trial (RCT), seeking to evaluate the effect of a weight reduction intervention on IVF outcome in obese women. Serum high-sensitivity C-reactive protein (hsCRP) and the adipokines leptin and adipocyte fatty acid-binding protein (AFABP) were analyzed for the whole cohort (n = 195) in samples collected shortly before IVF [at randomization (control group), after intervention (intervention group)]. Information on age, anthropometry [BMI, waist circumference, waist-to-height ratio (WHtR)], pregnancy and live birth rates after IVF, as well as the spontaneous pregnancy rate, was extracted or calculated from collected data. The women of the original intervention group were also characterized at randomization regarding all variables. Eight women [n = 3 original control group (2.3%), n = 5 original intervention group (7.8%)] conceived spontaneously before starting IVF. BMI category proportions in the cohort undergoing IVF (n = 187) were 1.6/20.1/78.3% (normal weight/overweight/obese). The pregnancy and live birth rates after IVF for the cohort were 35.8% (n = 67) and 24.6% (n = 46), respectively. Multivariable logistic regression revealed that none of the variables (age, hsCRP, leptin, AFABP, BMI, waist circumference, WHtR) were predictive factors of pregnancy or live birth after IVF. Women of the original intervention group displayed reductions in hsCRP, leptin, and anthropometric variables after intervention while AFABP was unchanged. In this cohort of predominantly overweight and obese women undergoing IVF, neither low-grade inflammation, in terms of hsCRP, other circulating inflammatory and metabolic markers released from adipose tissue (leptin, AFABP), nor anthropometric measures of adiposity or adipose tissue distribution (BMI, waist, WHtR) were identified as predictive factors of pregnancy or live birth rate.Trial registration: ClinicalTrials.gov number, NCT01566929. Trial registration date 30-03-2012, retrospectively registered.
Published: 2022
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4. Estimating and Characterizing COVID-19 Deaths, Puerto Rico, March–July 2020

Author: Diana Valencia, Maritza Cruz, Alejandro Azofeifa, Miguel Valencia-Prado, Joshua E Villafañe-Delgado, Edén Montañez-Báez, Betzaida Tejada-Vera, Devin Hayes, Carmen J Rodriguez, and Jessica J Cabrera
Subjects: Male, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 01 natural sciences, excess deaths, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, 030212 general & internal medicine, 0101 mathematics, SARS-CoV-2, business.industry, Research, Puerto Rico, 010102 general mathematics, Public Health, Environmental and Occupational Health, COVID-19, mortality, Virology, Epidemiological Monitoring, surveillance, Female, business
Abstract: Objectives Using the Council of State and Territorial Epidemiologists (CSTE) classification guidelines, we characterized coronavirus disease 2019 (COVID-19)–associated confirmed and probable deaths in Puerto Rico during March–July 2020. We also estimated the total number of possible deaths due to COVID-19 in Puerto Rico during the same period. Methods We described data on COVID-19–associated mortality, in which the lower bound was the sum of confirmed and probable COVID-19 deaths and the upper bound was excess mortality, estimated as the difference between observed deaths and average expected deaths. We obtained data from the Puerto Rico Department of Health COVID-19 Mortality Surveillance System, the Centers for Disease Control and Prevention’s National Electronic Disease Surveillance System Base System, and the National Center for Health Statistics. Results During March–July 2020, 225 COVID-19–associated deaths were identified in Puerto Rico (119 confirmed deaths and 106 probable deaths). The median age of decedents was 73 (interquartile range, 59-83); 60 (26.7%) deaths occurred in the Metropolitana region, and 140 (62.2%) deaths occurred among men. Of the 225 decedents, 180 (83.6%) had been hospitalized and 93 (41.3%) had required mechanical ventilation. Influenza and pneumonia (48.0%), sepsis (28.9%), and respiratory failure (27.1%) were the most common conditions contributing to COVID-19 deaths based on death certificates. Based on excess mortality calculations, as many as 638 COVID-19–associated deaths could have occurred during the study period, up to 413 more COVID-19–associated deaths than originally reported. Conclusions Including probable deaths per the CSTE guidelines and monitoring all-cause excess mortality can lead to a better estimation of COVID-19–associated deaths and serve as a model to enhance mortality surveillance in other US jurisdictions.
Published: 2021
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5. Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in Cushing’s syndrome

Author: Britt Edén Engström, Marlen Israelsson, Göran Brattsand, Oskar Ragnarsson, Jeanette Wahlberg, Tommy Olsson, Nils Bäcklund, Charlotte Höybye, Pia Burman, Per Dahlqvist, and Katarina Berinder
Subjects: Adult, Male, medicine.medical_specialty, Saliva, Time Factors, Hydrocortisone, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Diagnostic accuracy, Sensitivity and Specificity, Dexamethasone, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Reference Values, Tandem Mass Spectrometry, Internal medicine, medicine, Humans, Mass Screening, Cushing Syndrome, Salivary cortisol, Aged, Aged, 80 and over, S syndrome, business.industry, General Medicine, Middle Aged, Circadian Rhythm, Reference intervals, Cortisone, ROC Curve, Area Under Curve, 030220 oncology & carcinogenesis, Dexamethasone suppression test, Female, business, medicine.drug
Abstract: Objective The challenge of diagnosing Cushing’s syndrome (CS) calls for high precision biochemical screening. This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose (1 mg) dexamethasone suppression test (DST). Design and methods Saliva samples were collected at 08:00 and 23:00 h, and at 08:00 h, after a DST, from 22 patients with CS and from 155 adult reference subjects. We also collected samples at 20:00 and 22:00 h from 78 of the reference subjects. Salivary cortisol and cortisone were analysed with liquid chromatography-tandem mass spectrometry. The reference intervals were calculated as the 2.5th and 97.5th percentiles of the reference population measurements. Diagnostic accuracies of different tests were compared, based on areas under the receiver-operating characteristic curves. Results The upper reference limits of salivary cortisol and cortisone at 23:00 h were 3.6 nmol/L and 13.5 nmol/L, respectively. Using these reference limits, CS was detected with a sensitivity (95% CI) of 90% (70–99%) and specificity of 96% (91–98%) for cortisol, and a 100% (84–100%) sensitivity and 95% (90–98%) specificity for cortisone. After DST, cortisol and cortisone upper reference limits were 0.79 nmol/L and 3.5 nmol/L, respectively. CS was detected with 95% (75–100%) sensitivity and 96% (92–99%) specificity with cortisol, and 100% (83–100%) sensitivity and 94% (89–97%) specificity with cortisone. No differences in salivary cortisol or cortisone levels were found between samples collected at 22:00 and 23:00 h. Conclusion Salivary cortisol and cortisone in late-night samples and after DST showed high accuracy for diagnosing CS, salivary cortisone being slightly, but significantly better.
Published: 2020
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6. Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry

Author: Jitendra PS. Sawhney, Veerappa A. Kothiwale, Vikas Bisne, Rajashekhar Durgaprasad, Praveen Jadhav, Manoj Chopda, Velam Vanajakshamma, Ramdhan Meena, Govindan Vijayaraghavan, Kamaldeep Chawla, Jagan Allu, Karen S. Pieper, A. John Camm, Ajay K. Kakkar, Jean-Pierre Bassand, David A. Fitzmaurice, Samuel Z. Goldhaber, Shinya Goto, Sylvia Haas, Werner Hacke, Lorenzo G. Mantovani, Frank Misselwitz, Alexander G.G. Turpie, Martin van Eickels, Freek W.A. Verheugt, Gloria Kayani, Keith A.A. Fox, Bernard J. Gersh, Hector Lucas Luciardi, Harry Gibbs, Marianne Brodmann, Frank Cools, Antonio Carlos Pereira Barretto, Stuart J. Connolly, Alex Spyropoulos, John Eikelboom, Ramon Corbalan, Dayi Hu, Petr Jansky, Jørn Dalsgaard Nielsen, Hany Ragy, Pekka Raatikainen, Jean-Yves Le Heuzey, Harald Darius, Matyas Keltai, Sanjay Kakkar, Jitendra Pal Singh Sawhney, Giancarlo Agnelli, Giuseppe Ambrosio, Yukihiro Koretsune, Carlos Jerjes Sánchez Díaz, Hugo Ten Cate, Dan Atar, Janina Stepinska, Elizaveta Panchenko, Toon Wei Lim, Barry Jacobson, Seil Oh, Xavier Viñolas, Marten Rosenqvist, Jan Steffel, Pantep Angchaisuksiri, Ali Oto, Alex Parkhomenko, Wael Al Mahmeed, David Fitzmaurice, D.Y. Hu, K.N. Chen, Y.S. Zhao, H.Q. Zhang, J.Z. Chen, S.P. Cao, D.W. Wang, Y.J. Yang, W.H. Li, Y.H. Yin, G.Z. Tao, P. Yang, Y.M. Chen, S.H. He, Ying Wang, Yong Wang, G.S. Fu, X. Li, T.G. Wu, X.S. Cheng, X.W. Yan, R.P. Zhao, M.S. Chen, L.G. Xiong, P. Chen, Y. Jiao, Y. Guo, L. Xue, F.Z. Wang, H. Li, Z.M. Yang, C.L. Bai, J. Chen, J.Y. Chen, X. Chen, S. Feng, Q.H. Fu, X.J. Gao, W.N. Guo, R.H. He, X.A. He, X.S. Hu, X.F. Huang, B. Li, J. Li, L. Li, Y.H. Li, T.T. Liu, W.L. Liu, Y.Y. Liu, Z.C. Lu, X.L. Luo, T.Y. Ma, J.Q. Peng, X. Sheng, X.J. Shi, Y.H. Sun, G. Tian, K. Wang, L. Wang, R.N. Wu, Q. Xie, R.Y. Xu, J.S. Yang, L.L. Yang, Q. Yang, Y. Ye, H.Y. Yu, J.H. Yu, T. Yu, H. Zhai, Q. Zhan, G.S. Zhang, Q. Zhang, R. Zhang, Y. Zhang, W.Y. Zheng, B. Zhou, Z.H. Zhou, X.Y. Zhu, S. Kakkar, J.P.S. Sawhney, P. Jadhav, R. Durgaprasad, A.G. Ravi Shankar, R.K. Rajput, K. Bhargava, R. Sarma, A. Srinivas, D. Roy, U.M. Nagamalesh, M. Chopda, R. Kishore, G. Kulkarni, P. Chandwani, R.A. Pothiwala, M. Padinhare Purayil, S. Shah, K. Chawla, V.A. Kothiwale, B. Raghuraman, G. Vijayaraghavan, V.M. Vijan, G. Bantwal, V. Bisne, A. Khan, J.B. Gupta, S. Kumar, D. Jain, S. Abraham, D. Adak, A. Barai, H. Begum, P. Bhattacharjee, M. Dargude, D. Davies, B. Deshpande, P. Dhakrao, V. Dhyani, S. Duhan, M. Earath, A. Ganatra, S. Giradkar, V. Jain, R. Karthikeyan, L. Kasala, S. Kaur, S. Krishnappa, A. Lawande, B. Lokesh, N. Madarkar, R. Meena, P. More, D. Naik, K. Prashanth, M. Rao, N.M. Rao, N. Sadhu, D. Shah, M. Sharma, P. Shiva, S. Singhal, S. Suresh, V. Vanajakshamma, S.G. Panse, Y. Koretsune, S. Kanamori, K. Yamamoto, K. Kumagai, Y. Katsuda, K. Sadamatsu, F. Toyota, Y. Mizuno, I. Misumi, H. Noguchi, S. Ando, T. Suetsugu, M. Minamoto, Hiroshi Oda, K. Shiraishi, S. Adachi, K. Chiba, H. Norita, M. Tsuruta, T. Koyanagi, H. Ando, T. Higashi, K. Okada, S. Azakami, S. Komaki, K. Kumeda, T. Murayama, J. Matsumura, Y. Oba, R. Sonoda, K. Goto, K. Minoda, Y. Haraguchi, H. Suefuji, H. Miyagi, H. Kato, Tadashi Nakamura, Tsugihiro Nakamura, H. Nandate, R. Zaitsu, Yoshihisa Fujiura, A. Yoshimura, H. Numata, J. Ogawa, H. Tatematsu, Y. Kamogawa, K. Murakami, Y. Wakasa, M. Yamasawa, H. Maekawa, S. Abe, H. Kihara, S. Tsunoda, Katsumi Saito, Kazuyuki Saito, T. Fudo, K. Obunai, H. Tachibana, I. Oba, T. Kuwahata, S. Higa, M. Gushiken, T. Eto, H. Yoshida, D. Ikeda, Yoshitake Fujiura, M. Ishizawa, M. Nakatsuka, K. Murata, C. Ogurusu, M. Shimoyama, M. Akutsu, I. Takamura, F. Hoshino, N. Yokota, T. Iwao, K. Tsuchida, M. Takeuchi, Y. Hatori, Y. Kitami, Yoichi Nakamura, R. Oyama, M. Ageta, Hiroyuki Oda, Y. Go, K. Mishima, T. Unoki, S. Morii, Yuhei Shiga, H. Sumi, T. Nagatomo, K. Sanno, K. Fujisawa, Y. Atsuchi, T. Nagoshi, T. Seto, T. Tabuchi, M. Kameko, K. Nii, K. Oshiro, H. Takezawa, S. Nagano, N. Miyamoto, M. Iwaki, Yuichiro Nakamura, M. Fujii, M. Okawa, Masahiko Abe, Masatake Abe, Mitsunori Abe, T. Saito, T. Mito, K. Nagao, J. Minami, T. Mita, I. Sakuma, T. Taguchi, S. Marusaki, H. Doi, M. Tanaka, T. Fujito, M. Matsuta, T. Kusumoto, S. Kakinoki, K. Ashida, N. Yoshizawa, J. Agata, O. Arasaki, M. Manita, M. Ikemura, S. Fukuoka, H. Murakami, S. Matsukawa, Y. Hata, T. Taniguchi, T. Ko, H. Kubo, M. Imamaki, M. Akiyama, M. Inagaki, H. Odakura, T. Ueda, Y. Katsube, A. Nakata, H. Watanabe, M. Techigawara, M. Igarashi, K. Taga, T. Kimura, S. Tomimoto, M. Shibuya, M. Nakano, K. Ito, T. Seo, S. Hiramitsu, H. Hosokawa, M. Hoshiai, M. Hibino, K. Miyagawa, Hajime Horie, N. Sugishita, Yukio Shiga, A. Soma, K. Neya, Tetsuro Yoshida, Tomoki Yoshida, M. Mizuguchi, M. Ishiguro, T. Minagawa, M. Wada, H. Mukawa, F. Okuda, S. Nagasaka, Y. Abe, Sen Adachi, Susumu Adachi, T. Adachi, K. Akahane, T. Amano, K. Aoki, T. Aoyama, H. Arai, S. Arima, T. Arino, H. Asano, T. Asano, J. Azuma, T. Baba, T. Betsuyaku, H. Chibana, H. Date, J. Doiuchi, Y. Emura, M. Endo, Y. Fujii, R. Fujiki, A. Fujisawa, Y. Fujisawa, T. Fukuda, T. Fukui, N. Furukawa, T. Furukawa, W. Furumoto, T. Goto, M. Hamaoka, N. Hanazono, K. Hasegawa, T. Hatsuno, Y. Hayashi, K. Higuchi, K. Hirasawa, H. Hirayama, M. Hirose, S. Hirota, M. Honda, Hideki Horie, T. Ido, O. Iiji, H. Ikeda, K. Ikeda, K. Ikeoka, M. Imaizumi, H. Inaba, T. Inoue, F. Iseki, A. Ishihara, N. Ishioka, N. Ito, T. Iwase, H. Kakuda, J. Kamata, H. Kanai, H. Kanda, M. Kaneko, H. Kano, T. Kasai, T. Kato, Y. Kato, Y. Kawada, K. Kawai, K. Kawakami, S. Kawakami, T. Kawamoto, S. Kawano, J. Kim, T. Kira, H. Kitazawa, H. Kitazumi, T. Kito, T. Kobayashi, T. Koeda, J. Kojima, H. Komatsu, I. Komatsu, Y. Koshibu, T. Kotani, T. Kozuka, Y. Kumai, T. Kumazaki, I. Maeda, K. Maeda, Y. Maruyama, S. Matsui, K. Matsushita, Y. Matsuura, K. Mineoi, H. Mitsuhashi, N. Miura, S. Miyaguchi, S. Miyajima, H. Miyamoto, A. Miyashita, S. Miyata, I. Mizuguchi, A. Mizuno, T. Mori, O. Moriai, K. Morishita, O. Murai, Sho Nagai, Shunichi Nagai, E. Nagata, H. Nagata, A. Nakagomi, S. Nakahara, M. Nakamura, R. Nakamura, N. Nakanishi, T. Nakayama, R. Nakazato, T. Nanke, J. Nariyama, Y. Niijima, H. Niinuma, Y. Nishida, Y. Nishihata, K. Nishino, H. Nishioka, K. Nishizawa, I. Niwa, K. Nomura, S. Nomura, M. Nozoe, T. Ogawa, N. Ohara, M. Okada, K. Okamoto, H. Okita, M. Okuyama, H. Ono, T. Ono, Y. Onuki Pearce, S. Oriso, A. Ota, E. Otaki, Y. Saito, H. Sakai, N. Sakamoto, Y. Sakamoto, Y. Samejima, Y. Sasagawa, H. Sasaguri, A. Sasaki, T. Sasaki, Kazuki Sato, Kiyoharu Sato, M. Sawano, S. Seki, Y. Sekine, Y. Seta, K. Sezaki, N. Shibata, Y. Shiina, H. Shimono, Y. Shimoyama, T. Shindo, H. Shinohara, R. Shinohe, T. Shinozuka, T. Shirai, T. Shiraiwa, Y. Shozawa, T. Suga, C. Sugimoto, Kazuo Suzuki, Keita Suzuki, Shu Suzuki, Shunji Suzuki, Susumu Suzuki, Y. Suzuki, M. Tada, A. Taguchi, T. Takagi, Y. Takagi, K. Takahashi, S. Takahashi, H. Takai, C. Takanaka, S. Take, H. Takeda, K. Takei, K. Takenaka, T. Tana, G. Tanabe, K. Taya, H. Teragawa, S. Tohyo, S. Toru, Y. Tsuchiya, T. Tsuji, K. Tsuzaki, H. Uchiyama, O. Ueda, Y. Ueyama, N. Wakaki, T. Wakiyama, T. Washizuka, M. Watanabe, T. Yamada, T. Yamagishi, H. Yamaguchi, Kenichi Yamamoto, Kentaro Yamamoto, Kunihiko Yamamoto, T. Yamamoto, M. Yamaura, M. Yamazoe, K. Yasui, Y. Yokoyama, K. Yoshida, T.W. Lim, C.K. Ching, C.G. Foo, J.H. Chow, D.D. Chen, F.R. Jaufeerally, Y.M. Lee, G. Lim, W.T. Lim, S. Thng, S.Y. Yap, C. Yeo, S. Oh, H.N. Pak, J.-B. Kim, J.H. Kim, S.-W. Jang, D.H. Kim, D.R. Ryu, S.W. Park, D.-K. Kim, D.J. Choi, Y.S. Oh, M.-C. Cho, S.-H. Kim, H.-K. Jeon, D.-G. Shin, J.S. Park, H.K. Park, S.-J. Han, J.H. Sung, J.-G. Cho, G.-B. Nam, Y.K. On, H.E. Lim, J.J. Kwak, T.-J. Cha, T.J. Hong, S.H. Park, J.H. Yoon, N.-H. Kim, K.-S. Kim, B.C. Jung, G.-S. Hwang, C.-J. Kim, D.B. Kim, J.J. Ahn, H.J. An, H. Bae, A.L. Baek, W.J. Chi, E.A. Choi, E.H. Choi, H.K. Choi, H.S. Choi, S. Han, E.S. Heo, K.O. Her, S.W. Hwang, E.M. Jang, H.-S. Jang, S. Jang, H.-G. Jeon, S.R. Jeon, Y.R. Jeon, H.K. Jeong, I.-A. Jung, Hyeon Jeong Kim, Hyun Ju Kim, Ji Seon Kim, Jung Sook Kim, J.A. Kim, K.T. Kim, M.S. Kim, Sang Hee Kim, Sang Hyun Kim, Y.-I. Kim, C.S. Lee, E.H. Lee, G.H. Lee, H.Y. Lee, H.-Y. Lee, K.H. Lee, K.R. Lee, M.S. Lee, M.-Y. Lee, R.W. Lee, S.E. Lee, S.H. Lee, S. Lee, W.Y. Lee, I.K. Noh, A.R. Park, B.R. Park, H.N. Park, J.H. Park, M. Park, Y. Park, S.-Y. Seo, J. Shim, J.H. Sim, Y.M. Sohn, W.S. Son, Y.S. Son, H.J. Song, H.K. Wi, J.J. Woo, S. Ye, K.H. Yim, K.M. Yoo, E.J. Yoon, S.Y. Yun, P. Angchaisuksiri, S. Chawanadelert, P. Mongkolwongroj, K. Kanokphatcharakun, S. Cheewatanakornkul, T. Laksomya, S. Pattanaprichakul, T. Chantrarat, S. Rungaramsin, S. Silaruks, W. Wongcharoen, K. Siriwattana, K. Likittanasombat, P. Katekangplu, W. Boonyapisit, D. Cholsaringkarl, B. Chatlaong, P. Chattranukulchai, Y. Santanakorn, P. Hutayanon, P. Khunrong, T. Bunyapipat, S. Jai-Aue, P. Kaewsuwanna, P. Bamungpong, S. Gunaparn, S. Hongsuppinyo, R. Inphontan, R. Khattaroek, K. Khunkong, U. Kitmapawanont, C. Kongsin, B. Naratreekoon, S. Ninwaranon, J. Phangyota, A. Phrommintikul, P. Phunpinyosak, K. Pongmorakot, S. Poomiphol, N. Pornnimitthum, S. Pumprueg, S. Ratchasikaew, K. Sanit, K. Sawanyawisuth, B. Silaruks, R. Sirichai, A. Sriwichian, W. Suebjaksing, P. Sukklad, T. Suttana, A. Tangsirira, O. Thangpet, W. Tiyanon, Y. Vorasettakarnkij, T. Wisaratapong, W. Wongtheptien, A. Wutthimanop, S. Yawila, A. Oto, A. Altun, I. Ozdogru, K. Ozdemir, O. Yilmaz, A. Aydinlar, M.B. Yilmaz, E. Yeter, Z. Ongen, M. Cayli, H. Pekdemir, M. Ozdemir, M. Sucu, T. Sayin, M. Demir, H. 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Subjects: Registrie, Male, Time Factors, Anticoagulant therapy, Arrhythmia, Atrial fibrillation, GARFIELD-AF, 030204 cardiovascular system & hematology, Electrocardiography, 0302 clinical medicine, Risk Factors, Anticoagulant therapy, Arrhythmia, Atrial fibrillation, GARFIELD-AF, Aged, Atrial Fibrillation, Female, Follow-Up Studies, Humans, Incidence, India, Prevalence, Prognosis, Prospective Studies, Survival Rate, Thromboembolism, Registries, Risk Assessment, Medicine, 030212 general & internal medicine, Prospective cohort study, Incidence (epidemiology), cardiovascular system, medicine.symptom, Cardiology and Cardiovascular Medicine, Risk assessment, Human, medicine.medical_specialty, Time Factor, RD1-811, Prognosi, Follow-Up Studie, 03 medical and health sciences, Internal medicine, Diseases of the circulatory (Cardiovascular) system, cardiovascular diseases, Risk factor, Survival rate, Fibrillation, business.industry, Risk Factor, ta3121, medicine.disease, Clinical trial, Prospective Studie, RC666-701, Surgery, Clinical and Preventive Cardiology, business
Abstract: Background: The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. Methods and results: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012–2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P
Published: 2018
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7. Natural history and surgical outcome of Rathke's cleft cysts-A study from the Swedish Pituitary Registry

Author: Britt Edén Engström, Anna-Karin Åkerman, Maria Petersson, Katarina Berinder, Oskar Ragnarsson, Martin Olsson, Peter Siesjö, Jeanette Wahlberg, Petter Förander, Sophie Bensing, Henrik Borg, Erika Tsatsaris, Pia Burman, Bertil Ekman, Per Dahlqvist, and Charlotte Höybye
Subjects: medicine.medical_specialty, Pituitary gland, cyst size, hypopituitarism, pituitary, Rathkes cleft cyst, transphenoidal surgery, visual impairment, Endocrinology, Diabetes and Metabolism, Visual impairment, Hypopituitarism, Endocrinology and Diabetes, Asymptomatic, Endocrinology, Internal medicine, Medicine, Humans, Cyst, Pituitary Neoplasms, Registries, Central Nervous System Cysts, Sweden, Rathke's cleft cyst, business.industry, Kirurgi, medicine.disease, Surgery, Visual field, Natural history, medicine.anatomical_structure, Treatment Outcome, Pituitary Gland, Endokrinologi och diabetes, Female, medicine.symptom, Neoplasm Recurrence, Local, business
Abstract: Objective Rathkes cleft cysts are benign, embryological remnants in the pituitary gland. The majority of them are small and asymptomatic but a few may become large, and cause mass effects, pituitary hormone deficiencies and visual impairment. Recommendations for the follow-up of Rathkes cleft cysts vary since data on the natural history are sparse. Patients and Design Data at diagnosis and at 1, 5 and 10 years for patients with a Rathkes cleft cyst (434 at diagnosis, 317 females) were retrieved from the Swedish Pituitary Registry. Cysts = 10 mm that were not operated (n = 174) decreased in size over the years (p < .01). Pituitary hormone deficiencies and visual impairments were more frequent (18% and 5.7%, respectively) but were stable over time. Transphenoidal surgery was performed in 56 patients of whom 51 underwent surgery before the 1-year follow-up. The mean cyst diameter at diagnosis was 18 mm (range: 930 mm), 36% had pituitary hormone deficiency, 45% had visual field defects and 20% had impaired visual acuity. One year after surgery 60% had no cyst remnants, 50% had a pituitary deficiency, 26% had visual field defects and 12% had impaired visual acuity. No major changes were observed after 5 years. Twelve of the operated patients had a follow-up at 10 years, in eight the cyst remnants or recurrences increased in size over time (p < .05). Conclusions Rathkes cleft cysts with a size less than 10 mm rarely grow and our results indicate that radiological follow-up can be restricted to 5 years. In contrast, progression of postoperative remnants or recurrent cysts is more likely and require long-term follow-up.
Published: 2021

8. Overall and Disease-Specific Mortality in Patients With Cushing Disease: A Swedish Nationwide Study

Author: Pia Burman, Eva Marie Erfurth, Oskar Ragnarsson, Gudmundur Johannsson, Ing-Liss Bryngelsson, Katarina Berinder, Sophie Bensing, Elin Segerstedt, Maria Petersson, Anna-Karin Åkerman, David Petranek, Charlotte Höybye, Jeanette Wahlberg, Erik Schwarcz, Dimitrios Chantzichristos, Cecilia Follin, Britt Edén-Engström, Eleni Papakokkinou, Daniel S Olsson, Lorenza Bonelli, Bertil Ekman, Tommy Olsson, and Per Dahlqvist
Subjects: Adult, Male, medicine.medical_specialty, Pediatrics, Hormone Replacement Therapy, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, 030209 endocrinology & metabolism, Context (language use), Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, Humans, In patient, Pituitary ACTH Hypersecretion, Proportional Hazards Models, Retrospective Studies, Proportional hazards model, business.industry, Biochemistry (medical), Age specific mortality, Retrospective cohort study, Hormone replacement therapy (menopause), Middle Aged, Cushing Disease, Cardiovascular Diseases, 030220 oncology & carcinogenesis, Female, Observational study, business
Abstract: Whether patients with Cushing disease (CD) in remission have increased mortality is still debatable.To study overall and disease-specific mortality and predictive factors in an unselected nationwide cohort of patients with CD.A retrospective study of patients diagnosed with CD, identified in the Swedish National Patient Registry between 1987 and 2013. Medical records were systematically reviewed to verify the diagnosis. Standardized mortality ratios (SMRs) with 95% CIs were calculated and Cox regression models were used to identify predictors of mortality.Of 502 identified patients with CD (n = 387 women; 77%), 419 (83%) were confirmed to be in remission. Mean age at diagnosis was 43 (SD, 16) years and median follow-up was 13 (interquartile range, 6 to 23) years. The observed number of deaths was 133 vs 54 expected, resulting in an overall SMR of 2.5 (95% CI, 2.1 to 2.9). The commonest cause of death was cardiovascular diseases (SMR, 3.3; 95% CI, 2.6 to 4.3). Excess mortality was also found associated with infections and suicide. For patients in remission, the SMR was 1.9 (95% CI, 1.5 to 2.3); bilateral adrenalectomy and glucocorticoid replacement therapy were independently associated with increased mortality, whereas GH replacement was associated with improved outcome.Findings from this large nationwide study indicate that patients with CD have excess mortality. The findings illustrate the importance of achieving remission and continued active surveillance, along with adequate hormone replacement and evaluation of cardiovascular risk and mental health.
Published: 2019
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9. Corticotroph aggressive pituitary tumours and carcinomas frequently harbour ATRX mutations

Author: Paul Benjamin Loughrey, Chiara Villa, John R Lindsay, Olivera Casar-Borota, Miklós Tóth, Daniel Bengtsson, Charlotte Höybye, Britt Edén Engström, Martin Wirenfeldt, Ulla Feldt-Rasmussen, Oskar Ragnarsson, Emilija Manojlovic-Gacic, Henning B. Boldt, Camilla Schalin-Jäntti, Anders Jensen Kolnes, Jacek Kunicki, Dominique Maiter, David Scheie, Bertrand Baussart, Jens Pahnke, Marianne Andersen, Jens Otto Lunde Jørgensen, Pia Burman, Pietro Luigi Poliani, Márta Korbonits, Vera Popovic, Åse Krogh Rasmussen, Bertil Ekman, Katarina Berinder, HUS Abdominal Center, University of Helsinki, and Endokrinologian yksikkö
Subjects: Male, 0301 basic medicine, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, pituitary adenoma, pituitary carcinoma, Biochemistry, PATHWAY, Cohort Studies, 0302 clinical medicine, Endocrinology, Gene Frequency, TELOMERES, Corticotrophs, Clinical Laboratory Medicine, Genomics, Middle Aged, Cushing’s disease, EUROPEAN-SOCIETY, 3. Good health, Europe, Klinisk laboratoriemedicin, ACTH-Secreting Pituitary Adenoma, 030220 oncology & carcinogenesis, DAXX, Cushing's disease, Female, ATRX (alpha thalassemia/mental retardation syndrome X-linked), aggressive PitNETs, Cushings disease, AcademicSubjects/MED00250, EXPRESSION, Adenoma, Adult, X-linked Nuclear Protein, medicine.medical_specialty, GENES, Adolescent, 3122 Cancers, Nonsense mutation, Context (language use), CLASSIFICATION, Young Adult, 03 medical and health sciences, Death-associated protein 6, SDG 3 - Good Health and Well-being, Pituitary adenoma, Internal medicine, ADENOMAS, medicine, Humans, Genetic Predisposition to Disease, Neoplasm Invasiveness, Pituitary Neoplasms, Clinical Research Articles, ATRX, Aged, Cancer och onkologi, business.industry, Carcinoma, Biochemistry (medical), Pituitary tumors, Cancer, AMPLIFICATION, Neuroendocrinology, medicine.disease, 030104 developmental biology, Pituitary, 3121 General medicine, internal medicine and other clinical medicine, Cancer and Oncology, Mutation, Pituitary carcinoma, Cancer research, business
Abstract: Context Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs. Mutations in the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, regulating chromatin remodeling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumors. Objective To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs. Design We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumors lacking ATRX immunolabeling, mutational status of the ATRX gene was explored. Results Nine of the 48 tumors (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18; 28%) than in those with APTs (4/30;13%). Lack of ATRX was most common in the corticotroph tumors, 7/22 (32%), versus tumors of the Pit-1 lineage, 2/24 (8%). Loss-of-function ATRX mutations were found in all 9 ATRX immunonegative cases: nonsense mutations (n = 4), frameshift deletions (n = 4), and large deletions affecting 22-28 of the 36 exons (n = 3). More than 1 ATRX gene defect was identified in 2 PCs. Conclusion ATRX mutations occur in a subset of APTs and are more common in corticotroph tumors. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumors.
Published: 2021
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10. Psychotropic drugs in patients with Cushing's disease before diagnosis and at long-term follow-up - a nationwide study

Author: Daniel Bengtsson, Per Dahlqvist, Katarina Berinder, Britt Edén Engström, Bertil Ekman, Jeanette Wahlberg, Oskar Ragnarsson, Pia Burman, and Charlotte Höybye
Subjects: Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Cushing's syndrome, 030209 endocrinology & metabolism, Context (language use), Subgroup analysis, Endocrinology and Diabetes, Biochemistry, Psykiatri, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Interquartile range, Internal medicine, Diabetes mellitus, medicine, Humans, neuropsychiatry, Longitudinal Studies, Pituitary ACTH Hypersecretion, Depression (differential diagnoses), Retrospective Studies, Sweden, Psychiatry, Psychotropic Drugs, hypercortisolism, business.industry, Mental Disorders, Biochemistry (medical), Odds ratio, Cushing's disease, Middle Aged, medicine.disease, Cross-Sectional Studies, Cushing’s syndrome, Pill, depression, sleeping disorder, Endokrinologi och diabetes, Female, Morbidity, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Context Psychiatric symptoms are common in Cushing’s disease (CD) and seem only partly reversible following treatment. Objective To investigate drug dispenses associated to psychiatric morbidity in CD patients before treatment and during long-term follow-up. Design Nationwide longitudinal register-based study. Setting University Hospitals in Sweden. Subjects CD patients diagnosed between 1990 and 2018 (N = 372) were identified in the Swedish Pituitary Register. Longitudinal data was collected from 5 years before, at diagnosis, and during follow-up. Four matched controls per patient were included. Cross-sectional subgroup analysis of 76 patients in sustained remission was also performed. Main outcome measures Data from the Swedish Prescribed Drug Register and the Patient Register. Results In the 5-year period before and at diagnosis, use of antidepressants (odds ratio [OR] 2.2 [95% confidence interval (CI) 1.3-3.7]) and 2.3 [1.6-3.5]), anxiolytics [2.9 (1.6-5.3) and 3.9 (2.3-6.6)], and sleeping pills [2.1 (1.2-3.7) and 3.8 (2.4-5.9)] was more common in CD than controls. ORs remained elevated at 5-year follow-up for antidepressants [2.4 (1.5-3.9)] and sleeping pills [3.1 (1.9-5.3)]. Proportions of CD patients using antidepressants (26%) and sleeping pills (22%) were unchanged at diagnosis and 5-year follow-up, whereas drugs for hypertension and diabetes decreased. Patients in sustained remission for median 9.3 years (interquartile range 8.1-10.4) had higher use of antidepressants [OR 2.0 (1.1-3.8)] and sleeping pills [2.4 (1.3-4.7)], but not of drugs for hypertension. Conclusions Increased use of psychotropic drugs in CD was observed before diagnosis and remained elevated regardless of remission status, suggesting persisting negative effects on mental health. The study highlights the importance of early diagnosis of CD, and the need for long-term monitoring of mental health.
Published: 2021

11. Histopathological findings in the landscape of IgG4-related pathology in patients with pituitary dysfunction : Review of six cases

Author: Britt Edén Engström, Lilian Vasaitis, Eva Kumlien, Johan Wikström, Olivera Casar-Borota, Olafur Gudjonsson, and Sengul Ahlström
Subjects: Male, Pituitary gland, Pathology, Pituitary disease, Endocrinology, Diabetes and Metabolism, IgG4-related hypophysitis, 0302 clinical medicine, Endocrinology, pituitary inflammation, Autoimmune Hypophysitis, Cyst, Overdiagnosis, Central Nervous System Cysts, skin and connective tissue diseases, medicine.diagnostic_test, integumentary system, Clinical Laboratory Medicine, Headache, Middle Aged, Magnetic Resonance Imaging, Klinisk laboratoriemedicin, Treatment Outcome, medicine.anatomical_structure, Pituitary Gland, Female, Adult, medicine.medical_specialty, Hormone Replacement Therapy, Hypophysitis, Plasma Cells, 030209 endocrinology & metabolism, 03 medical and health sciences, Cellular and Molecular Neuroscience, Biopsy, parasitic diseases, medicine, Humans, Aged, Inflammation, Cancer och onkologi, Rathke's cleft cyst, criteria, Endocrine and Autonomic Systems, business.industry, fungi, medicine.disease, Immunoglobulin G, Cancer and Oncology, Histopathology, business, Diabetes Insipidus, 030217 neurology & neurosurgery
Abstract: IgG4-related hypophysitis (IgG4-RH) is increasingly being reported as an isolated entity or, less frequently, as a manifestation of a multiorgan IgG4-related disease (IgG4-RD), in which typical histopathology is a cornerstone for the diagnosis. We aimed to describe the histopathological changes in the surgical specimens from patients with clinical signs of pituitary disease that fulfilled the current diagnostic criteria for IgG4-RH. Histopathological features were correlated with clinical and radiological findings. Of 19 patients with pituitary dysfunction and inflammatory changes in the surgical pituitary specimen operated on during 2011-2019, we identified five patients with typical IgG4-related pathology (lymphoplasmacytic infiltration with more than 10 IgG4-positive plasma cells per one high power microscopic field, representing at least 40% of all plasma cells and at least focal storiform fibrosis). One patient with diabetes insipidus and pachymeningitis with IgG4-related changes in a biopsy from the dura was also included. Additional histopathological changes that typically are not part of the IgG4-RH were observed: Rathke's cleft cyst in four and granulomatous changes in two patients. One patient had an elevated serum IgG4 level and systemic manifestations that could be associated with the systemic IgG4-RD. Our findings indicate that pure IgG4-RH is uncommon. All patients with pituitary dysfunction, beyond typical IgG4-related pathology, had other pathological findings that could trigger the secondary IgG4-response. Both primary pathology and secondary IgG4-related features should be reported in patients with pituitary dysfunction because their co-occurrence may cause atypical clinical and imaging features, and unexpected response to surgical and pharmacological treatment. The current criteria for the diagnosis of IgG4-RH can lead to overdiagnosis of IgG4-RH if additional pathological changes are not taken into consideration. The classification criteria of IgG4-RD proposed by the American College of Rheumatology/European League Against Rheumatism could help classify patients more properly as IgG4-RH if applied to the pituitary gland.
Published: 2021

12. Viral Antigen and Inflammatory Biomarkers in Cerebrospinal Fluid in Patients With COVID-19 Infection and Neurologic Symptoms Compared With Control Participants Without Infection or Neurologic Symptoms

Author: Arvid Edén, Anna Grahn, Daniel Bremell, Anahit Aghvanyan, Pradeepthi Bathala, Dietmar Fuchs, Johanna Gostner, Lars Hagberg, Nelly Kanberg, Sunsanee Kanjananimmanont, Magnus Lindh, Salvia Misaghian, Staffan Nilsson, Michael Schöll, George Sigal, Erika Stentoft, Marie Studahl, Aylin Yilmaz, Mingyue Wang, Martin Stengelin, Henrik Zetterberg, and Magnus Gisslén
Subjects: Adult, Male, SARS-CoV-2, COVID-19, General Medicine, Middle Aged, Neopterin, Interferon-gamma, Cross-Sectional Studies, Neurofilament Proteins, Humans, RNA, Viral, Female, Antigens, Viral, Biomarkers
Abstract: Neurologic symptoms are common in COVID-19, but the central nervous system (CNS) pathogenesis is unclear, and viral RNA is rarely detected in cerebrospinal fluid (CSF).To measure viral antigen and inflammatory biomarkers in CSF in relation to neurologic symptoms and disease severity.This cross-sectional study was performed from March 1, 2020, to June 30, 2021, in patients 18 years or older who were admitted to Sahlgrenska University Hospital, Gothenburg, Sweden, with COVID-19. All patients had CSF samples taken because of neurologic symptoms or within a study protocol. Healthy volunteer and prepandemic control groups were included.SARS-CoV-2 infection.Outcomes included CSF SARS-CoV-2 nucleocapsid antigen (N-Ag) using an ultrasensitive antigen capture immunoassay platform and CSF biomarkers of immune activation (neopterin, β2-microglobulin, and cytokines) and neuronal injury (neurofilament light protein [NfL]).Forty-four patients (median [IQR] age, 57 [48-69] years; 30 [68%] male; 26 with moderate COVID-19 and 18 with severe COVID-19 based on the World Health Organization Clinical Progression Scale), 10 healthy controls (median [IQR] age, 58 [54-60] years; 5 [50%] male), and 41 patient controls (COVID negative without evidence of CNS infection) (median [IQR] age, 59 [49-70] years; 19 [46%] male) were included in the study. Twenty-one patients were neuroasymptomatic and 23 were neurosymptomatic (21 with encephalopathy). In 31 of 35 patients for whom data were available (89%), CSF N-Ag was detected; viral RNA test results were negative in all. Nucleocapsid antigen was significantly correlated with CSF neopterin (r = 0.38; P = .03) and interferon γ (r = 0.42; P = .01). No differences in CSF N-Ag concentrations were found between patient groups. Patients had markedly increased CSF neopterin, β2-microglobulin, interleukin (IL) 2, IL-6, IL-10, and tumor necrosis factor α compared with controls. Neurosymptomatic patients had significantly higher median (IQR) CSF interferon γ (86 [47-172] vs 21 [17-81] fg/mL; P = .03) and had a significantly higher inflammatory biomarker profile using principal component analysis compared with neuroasymptomatic patients (0.54; 95% CI, 0.03-1.05; P = .04). Age-adjusted median (IQR) CSF NfL concentrations were higher in patients compared with controls (960 [673-1307] vs 618 [489-786] ng/L; P = .002). No differences were seen in any CSF biomarkers in moderate compared with severe disease.In this study of Swedish adults with COVID-19 infection and neurologic symptoms, compared with control participants, viral antigen was detectable in CSF and correlated with CNS immune activation. Patients with COVID-19 had signs of neuroaxonal injury, and neurosymptomatic patients had a more marked inflammatory profile that could not be attributed to differences in COVID-19 severity. These results highlight the clinical relevance of neurologic symptoms and suggest that viral components can contribute to CNS immune responses without direct viral invasion.
Published: 2022
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13. CSF Biomarkers in Patients With COVID-19 and Neurologic Symptoms: A Case Series

Author: Dietmar Fuchs, Lars Andersson, Arvid Edén, Richard W. Price, Nelly Kanberg, Henrik Zetterberg, Lars Hagberg, Magnus Lindh, Magnus Gisslén, and Johanna M. Gostner
Subjects: Adult, Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Inflammation, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cerebrospinal fluid, White blood cell, Internal medicine, Medicine, Humans, 030212 general & internal medicine, Aged, Aged, 80 and over, business.industry, SARS-CoV-2, Albumin, Neopterin, COVID-19, Middle Aged, medicine.disease, Dysgeusia, medicine.anatomical_structure, chemistry, Blood-Brain Barrier, Female, Neurology (clinical), medicine.symptom, Nervous System Diseases, business, Meningitis, 030217 neurology & neurosurgery, Biomarkers
Abstract: ObjectiveTo explore whether hospitalized patients with SARS-CoV-2 and neurologic symptoms have evidence of CNS infection, inflammation and injury using CSF biomarker measurements.MethodsWe assessed CSF SARS-CoV-2 RNA along with CSF biomarkers of intrathecal inflammation (CSF white blood cell count, neopterin, β2-microglobulin (β2M) and immunoglobulin G-index), blood-brain-barrier (BBB) integrity (albumin ratio), and axonal injury (CSF neurofilament light chain protein [NfL]) in 6 patients with moderate to severe COVID-19 and neurologic symptoms who had undergone a diagnostic lumbar puncture. Neurologic symptoms and signs included features of encephalopathies (4/6), suspected meningitis (1/6) and dysgeusia (1/6). SARS-CoV-2 infection was confirmed by rtPCR analysis of nasopharyngeal swabs.ResultsSARS-CoV-2 RNA was detected in the plasma of 2 patients (Cycle threshold [Ct] value 35.0–37.0) and in CSF at low levels (Ct 37.2, 38.0, 39.0) in 3 patients in one but not in a second rtPCR assay. CSF neopterin (median, 43.0 nmol/L) and β2-microglobulin (median, 3.1 mg/L) were increased in all. Median IgG-index (0.39), albumin ratio (5.35) and CSF white blood cell count (ConclusionOur results on patients with COVID-19 and neurologic symptoms suggest an unusual pattern of marked CSF inflammation in which soluble markers were increased but white cell response and other immunologic features typical of CNS viral infections were absent. While our initial hypothesis centered on CNS SARS-CoV-2 invasion, we could not convincingly detect SARS-CoV-2 as the underlying driver of CNS inflammation. These features distinguish COVID-19 CSF from other viral CNS infections, and raise fundamental questions about the CNS pathobiology of SARS-CoV-2 infection.
Published: 2020

14. Improved Urinary Cortisol Metabolome in Addison Disease: A Prospective Trial of Dual-Release Hydrocortisone

Author: Stéphanie, Espiard, Johanna, McQueen, Mark, Sherlock, Oskar, Ragnarsson, Ragnhildur, Bergthorsdottir, Pia, Burman, Per, Dahlqvist, Bertil, Ekman, Britt Edén, Engström, Stanko, Skrtic, Jeanette, Wahlberg, Paul M, Stewart, and Gudmundur, Johannsson
Subjects: Adult, Male, Cross-Over Studies, Hydrocortisone, cortisol metabolism, 11β-hydroxysteroid dehydrogenase, Middle Aged, Urinalysis, Pregnanes, Cortisone, Europe, Addison Disease, dual-release hydrocortisone, Delayed-Action Preparations, Tetrahydrocortisone, primary adrenal insufficiency, Metabolome, Humans, Female, Steroids, Tetrahydrocortisol, AcademicSubjects/MED00250, Clinical Research Articles, Aged
Abstract: Context Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy has demonstrated an improved metabolic profile compared to conventional 3-times-daily (TID-HC) therapy among patients with primary adrenal insufficiency. This effect might be related to a more physiological cortisol profile, but also to a modified pattern of cortisol metabolism. Objective This work aimed to study cortisol metabolism during DR-HC and TID-HC. Design A randomized, 12-week, crossover study was conducted. Intervention and Participants DC-HC and same daily dose of TID-HC were administered to patients with primary adrenal insufficiency (n = 50) vs healthy individuals (n = 124) as controls. Main Outcome Measures Urinary corticosteroid metabolites were measured by gas chromatography/mass spectrometry at 24-hour urinary collections. Results Total cortisol metabolites decreased during DR-HC compared to TID-HC (P
Published: 2020

15. Excess Morbidity Persists in Patients With Cushing's Disease During Long-term Remission: A Swedish Nationwide Study

Author: Bertil Ekman, Erik Schwarcz, Tommy Olsson, Daniel S Olsson, Eva Marie Erfurth, Per Dahlqvist, Sophie Bensing, Charlotte Höybye, Pia Burman, Eleni Papakokkinou, Dimitrios Chantzichristos, Maria Petersson, Cecilia Follin, David Petranek, Jeanette Wahlberg, Ing Liss Bryngelsson, Lorenza Bonelli, Katarina Berinder, Elin Segerstedt, Anna Karin Åkerman, Oskar Ragnarsson, Gudmundur Johannsson, and Britt Edén-Engström
Subjects: Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Deep vein, Clinical Biochemistry, Population, 030209 endocrinology & metabolism, Context (language use), Comorbidity, Biochemistry, Medical Records, 03 medical and health sciences, Fractures, Bone, 0302 clinical medicine, Endocrinology, Interquartile range, Risk Factors, Internal medicine, Neoplasms, Sepsis, Thromboembolism, medicine, Humans, education, Pituitary ACTH Hypersecretion, Stroke, Glucocorticoids, Aged, Retrospective Studies, Sweden, education.field_of_study, business.industry, Incidence (epidemiology), Incidence, Biochemistry (medical), Remission Induction, Cushing's disease, Middle Aged, medicine.disease, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, business, Follow-Up Studies
Abstract: Context Whether multisystem morbidity in Cushing’s disease (CD) remains elevated during long-term remission is still undetermined. Objective To investigate comorbidities in patients with CD. Design, Setting, and Patients A retrospective, nationwide study of patients with CD identified in the Swedish National Patient Register between 1987 and 2013. Individual medical records were reviewed to verify diagnosis and remission status. Main Outcomes Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by using the Swedish general population as reference. Comorbidities were investigated during three different time periods: (i) during the 3 years before diagnosis, (ii) from diagnosis to 1 year after remission, and (iii) during long-term remission. Results We included 502 patients with confirmed CD, of whom 419 were in remission for a median of 10 (interquartile range 4 to 21) years. SIRs (95% CI) for myocardial infarction (4.4; 1.2 to 11.4), fractures (4.9; 2.7 to 8.3), and deep vein thrombosis (13.8; 3.8 to 35.3) were increased during the 3-year period before diagnosis. From diagnosis until 1 year after remission, SIRs (95% CI were increased for thromboembolism (18.3; 7.9 to 36.0), stroke (4.9; 1.3 to 12.5), and sepsis (13.6; 3.7 to 34.8). SIRs for thromboembolism (4.9; 2.6 to 8.4), stroke (3.1; 1.8 to 4.9), and sepsis (6.0; 3.1 to 10.6) remained increased during long-term remission. Conclusion Patients with CD have an increased incidence of stroke, thromboembolism, and sepsis even after remission, emphasizing the importance of early identification and management of risk factors for these comorbidities during long-term follow-up.
Published: 2020

16. Persistent central nervous system immune activation following more than 10 years of effective HIV antiretroviral treatment

Author: Aylin Yilmaz, Dietmar Fuchs, Lars Hagberg, Magnus Gisslén, Gustaf Ulfhammer, Henrik Zetterberg, Arvid Edén, Staffan Nilsson, and Åsa Mellgren
Subjects: Adult, Central Nervous System, Male, 0301 basic medicine, medicine.medical_specialty, AIDS Dementia Complex, Sustained Virologic Response, Immunology, Central nervous system, Human immunodeficiency virus (HIV), HIV Infections, Neuropsychological Tests, medicine.disease_cause, Neopterin, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cerebrospinal fluid, Neurofilament Proteins, Internal medicine, Humans, Immunology and Allergy, Medicine, Clinical significance, Longitudinal Studies, Aged, Retrospective Studies, business.industry, Retrospective cohort study, Middle Aged, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, Anti-Retroviral Agents, chemistry, RNA, Viral, Female, business, Neurocognitive, 030217 neurology & neurosurgery, Immune activation
Abstract: Objective: Low-grade immune activation is common in people living with HIV (PLHIV), despite long-term viral suppression by antiretroviral therapy (ART). The clinical significance of this activation remains unclear. The aim of this study was to examine residual intrathecal immune activation in relation to signs of neuronal injury and neurocognitive impairment in PLHIV who had been virally suppressed on ART for more than 10 years. Design/methods: Twenty neuroasymptomatic PLHIV on suppressive ART for a median of 13.2 years were retrospectively identified from the longitudinal prospective Gothenburg HIV cerebrospinal fluid (CSF) study. HIV-RNA, neopterin, and neurofilament light protein (NFL) levels were measured in paired plasma and CSF samples. Pretreatment samples were available for 14 patients. Cognitive function was assessed by CogState at follow-up. Results: CSF neopterin decreased from a median (IQR) of 17.8 (10.6 - 29.7) to 6.1 (4.6 - 8.0) nmol/l during treatment (P < 0.001). In 11 out of 20 participants (55%), CSF neopterin levels were above the upper normal reference limit (5.8 nmol/l) at followup. Age-adjusted CSF NFL decreased to within-normal levels from a median of (IQR) 1179 (557 - 2707) to 415 (292 - 610) ng/l (P < 0.001). No significant correlations were found between CSF neopterin and CSF NFL or neurocognitive performance. Conclusion: Although CSF neopterin decreased significantly, more than 50% of the patients had CSF concentrations above the upper normal reference value despite more than 10 years of suppressive ART. We found no correlation between CSF neopterin, CSF NFL or neurocognitive performance at follow-up, indicating that low-grade immune activation during suppressive ART may be clinically benign.
Published: 2018
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17. A multicenter study investigating the molecular fingerprint of psychological resilience in breast cancer patients: study protocol of the SCAN-B resilience study

Author: Lisa Rydén, Ulrika Axelsson, Johanna Månsson, Carl A.K. Borrebaeck, Ingalill Rahm Hallberg, Patrik Edén, and Per Johnsson
Subjects: Proteomics, Gerontology, Cancer Research, Time Factors, Study Protocol, 0302 clinical medicine, Breast cancer, Cost of Illness, Quality of life, Surveys and Questionnaires, Adaptation, Psychological, Multicenter Studies as Topic, Medicine, Prospective Studies, 030212 general & internal medicine, media_common, Psychological resilience, Genomics, Resilience, Psychological, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Oncology, 030220 oncology & carcinogenesis, Epigenetics, Female, Psychosocial, media_common.quotation_subject, SF36, Breast Neoplasms, lcsh:RC254-282, 03 medical and health sciences, Predictive Value of Tests, Biomarkers, Tumor, Genetics, Humans, Socioeconomic status, Disease burden, Sweden, business.industry, Gene Expression Profiling, Cancer, medicine.disease, Omics, Body and mind, CD-RISC, business, Biomolecular parameters
Abstract: Background Individual patients differ in their psychological response when receiving a cancer diagnosis, in this case breast cancer. Given the same disease burden, some patients master the situation well, while others experience a great deal of stress, depression and lowered quality of life. Patients with high psychological resilience are likely to experience fewer stress reactions and better adapt to and manage the life threat and the demanding treatment that follows the diagnosis. If this phenomenon of mastering difficult situations is reflected also in biomolecular processes is not much studied, nor has its capacity for impacting the cancer prognosis been addressed. This project specifically aims, for the first time, to investigate how a breast cancer patient’s psychological resilience is coupled to biomolecular parameters using advanced “omics” and, as a secondary aim, whether it relates to prognosis and quality of life one year after diagnosis. Method The study population consists of newly diagnosed breast cancer patients enrolled in the Sweden Cancerome Analysis Network – Breast (SCAN-B) at four hospitals in Sweden. At the time of cancer diagnosis, the patient fills out the standardized method to measure psychological resilience, the “Connor-Davidson Resilience scale” (CD-RISC), the quality of life measure SF-36, as well as providing social and socioeconomic variables. In addition, one blood sample is collected. At the one-year follow-up, the patient will be subjected to the same assessments, and we also collect information regarding smoking, exercise habits, and BMI, as well as patients’ trust in the treatment and their satisfaction with the care and treatment. Discussion This explorative hypothesis-generating project will pave the way for larger validation studies, potentially leading to a standardized method of measuring psychological resilience as an important parameter in cancer care. Revealing the body-mind interaction, in terms of psychological resilience and quality of life, will herald the development of truly personalized psychosocial care and cancer intervention treatment strategies. Trial registration This is a retrospectively registered trial at ClinicalTrials.gov, ID: NCT03430492 on February 6, 2018. Electronic supplementary material The online version of this article (10.1186/s12885-018-4669-y) contains supplementary material, which is available to authorized users.
Published: 2018
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18. Neurochemical signs of astrocytic and neuronal injury in acute COVID-19 normalizes during long-term follow-up

Author: Nelly Kanberg, Staffan Nilsson, Pär-Daniel Sundvall, Lars-Magnus Andersson, Joel Simrén, Kaj Blennow, Arvid Edén, Magnus Gisslén, Henrik Zetterberg, Bengt Nellgård, and Nicholas J. Ashton
Subjects: Male, Medicine (General), medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), GFAp, Long term follow up, Disease, Plasma biomarkers, Gastroenterology, General Biochemistry, Genetics and Molecular Biology, R5-920, Neurochemical, Neurofilament Proteins, Internal medicine, Glial Fibrillary Acidic Protein, Humans, Medicine, Longitudinal Studies, Aged, Neurons, Sweden, Glial fibrillary acidic protein, biology, SARS-CoV-2, business.industry, COVID-19, General Medicine, Middle Aged, NfL, GDF-15, Clinical research, Astrocytes, Disease Progression, biology.protein, Female, GDF15, CNS, business, Biomarkers, Research Paper, Follow-Up Studies
Abstract: Background: Neurologic manifestations are well-recognized features of coronavirus disease 2019 (COVID-19). However, the longitudinal association of biomarkers reflecting CNS impact and neurological symptoms is not known. We sought to determine whether plasma biomarkers of CNS injury were associated with neurologic sequelae after COVID-19. Methods: Patients with confirmed acute COVID-19 were studied prospectively. Neurological symptoms were recorded during the acute phase of the disease and at six months follow-up, and blood samples were collected longitudinally. Healthy age-matched individuals were included as controls. We analysed plasma concentrations of neurofilament light-chain (NfL), glial fibrillary acidic protein (GFAp), and growth differentiation factor 15 (GDF-15). Findings: One hundred patients with mild (n = 24), moderate (n = 28), and severe (n = 48) COVID-19 were followed for a median (IQR) of 225 (187–262) days. In the acute phase, patients with severe COVID-19 had higher concentrations of NfL than all other groups (all p < 0·001), and higher GFAp than controls (p < 0·001). GFAp was also significantly increased in moderate disease (p < 0·05) compared with controls. NfL (r = 0·53, p < 0·001) and GFAp (r = 0·39, p < 0·001) correlated with GDF-15 during the acute phase. After six months, NfL and GFAp concentrations had normalized, with no persisting group differences. Despite this, 50 patients reported persistent neurological symptoms, most commonly fatigue (n = 40), “brain-fog” (n = 29), and changes in cognition (n = 25). We found no correlation between persistent neurological symptoms and CNS injury biomarkers in the acute phase. Interpretation: The normalization of CNS injury biomarkers in all individuals, regardless of previous disease severity or persisting neurological symptoms, indicates that post COVID-19 neurological sequelae are not accompanied by ongoing CNS injury. Funding: The Swedish State Support for Clinical Research, SciLifeLab Sweden, and the Knut and Alice Wallenberg Foundation have provided funding for this project.
Published: 2021
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19. Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: a phase 3b, open-label, extension study

Author: Bertil Ekman, Pia Burman, Claudio Marelli, Sharif Uddin, Ragnhildur Bergthorsdottir, Heinrich Achenbach, Oskar Ragnarsson, Britt Edén Engström, Gudmundur Johannsson, Per Dahlqvist, Anna G Nilsson, Jeanette Wahlberg, and Stanko Skrtic
Subjects: Adult, Male, medicine.medical_specialty, Hydrocortisone, Hormone Replacement Therapy, Endocrinology, Diabetes and Metabolism, General Practice, 030209 endocrinology & metabolism, Endocrinology and Diabetes, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Addison Disease, Internal medicine, medicine, Adrenal insufficiency, Humans, In patient, Longitudinal Studies, 030212 general & internal medicine, Glucocorticoids, Fatigue, Aged, Sweden, business.industry, Kirurgi, Extension study, General Medicine, Middle Aged, medicine.disease, Gastroenteritis, Allmänmedicin, Clinical trial, Treatment Outcome, Tolerability, Nasopharyngitis, Delayed-Action Preparations, Endokrinologi och diabetes, Clinical Study, Quality of Life, Surgery, Female, Long term safety, business, Glucocorticoid, medicine.drug
Abstract: Objective To investigate the long-term safety and tolerability of a once-daily, dual-release hydrocortisone (DR-HC) tablet as oral glucocorticoid replacement therapy in patients with primary adrenal insufficiency (AI). Design Prospective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden. Methods Seventy-one adult patients diagnosed with primary AI who were receiving stable glucocorticoid replacement therapy were recruited. Safety and tolerability outcomes included adverse events (AEs), intercurrent illness episodes, laboratory parameters and vital signs. Quality of life (QoL) was evaluated using generic questionnaires. Results Total DR-HC exposure was 328 patient-treatment years. Seventy patients reported 1060 AEs (323 per 100 patient-years); 85% were considered unrelated to DR-HC by the investigator. The most common AEs were nasopharyngitis (70%), fatigue (52%) and gastroenteritis (48%). Of 65 serious AEs reported by 32 patients (20 per 100 patient-years), four were considered to be possibly related to DR-HC: acute AI (n = 2), gastritis (n = 1) and syncope (n = 1). Two deaths were reported (fall from height and subarachnoid hemorrhage), both considered to be unrelated to DR-HC. From baseline to 5 years, intercurrent illness episodes remained relatively stable (mean 2.6–5.4 episodes per patient per year), fasting plasma glucose (0.7 mmol/L; P P P = 0.008). Conclusions In the first prospective study evaluating the long-term safety of glucocorticoid replacement therapy in patients with primary AI, DR-HC was well tolerated with no safety concerns observed during 5-year treatment.
Published: 2017
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20. Artificial neural network models to predict nodal status in clinically node-negative breast cancer

Author: Lisa Rydén, Pär-Ola Bendahl, Mattias Ohlsson, Looket Dihge, and Patrik Edén
Subjects: 0301 basic medicine, Cancer Research, Logistic regression, Breast cancer, 0302 clinical medicine, Sentinel lymph node biopsy, Estrogen Receptor Status, Aged, 80 and over, Artificial neural networks, Neovascularization, Pathologic, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Tumor Burden, medicine.anatomical_structure, Receptors, Estrogen, Oncology, Area Under Curve, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Female, Radiology, Research Article, Adult, medicine.medical_specialty, Nodal status, Sentinel lymph node, Breast Neoplasms, Prediction models, lcsh:RC254-282, Young Adult, 03 medical and health sciences, Genetics, medicine, Humans, Aged, Retrospective Studies, Receiver operating characteristic, business.industry, Cancer, Retrospective cohort study, medicine.disease, Carcinoma, Lobular, Axilla, 030104 developmental biology, Linear Models, Lymph Nodes, Neural Networks, Computer, business
Abstract: Background Sentinel lymph node biopsy (SLNB) is standard staging procedure for nodal status in breast cancer, but lacks therapeutic benefit for patients with benign sentinel nodes. For patients with positive sentinel nodes, individualized surgical strategies are applied depending on the extent of nodal involvement. Preoperative prediction of nodal status is thus important for individualizing axillary surgery avoiding unnecessary surgery. We aimed to predict nodal status in clinically node-negative breast cancer and identify candidates for SLNB omission by including patient-related and pathological characteristics into artificial neural network (ANN) models. Methods Patients with primary breast cancer were consecutively included between January 1, 2009 and December 31, 2012 in a prospectively maintained pathology database. Clinical- and radiological data were extracted from patient’s files and only clinically node-negative patients constituted the final study cohort. ANN-based models for nodal prediction were constructed including 15 risk variables for nodal status. Area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow goodness-of-fit test (HL) were used to assess performance and calibration of three predictive ANN-based models for no lymph node metastasis (N0), metastases in 1–3 lymph nodes (N1) and metastases in ≥ 4 lymph nodes (N2). Linear regression models for nodal prediction were calculated for comparison. Results Eight hundred patients (N0, n = 514; N1, n = 232; N2, n = 54) were included. Internally validated AUCs for N0 versus N+ was 0.740 (95% CI = 0.723–0.758); median HL was 9.869 (P = 0.274), for N1 versus N0, 0.705 (95% CI = 0.686–0.724; median HL: 7.421; P = 0.492) and for N2 versus N0 and N1, 0.747 (95% CI = 0.728–0.765; median HL: 9.220; P = 0.324). Tumor size and vascular invasion were top-ranked predictors of all three end-points, followed by estrogen receptor status and lobular cancer for prediction of N2. For each end-point, ANN models showed better discriminatory performance than multivariable logistic regression models. Accepting a false negative rate (FNR) of 10% for predicting N0 by the ANN model, SLNB could have been abstained in 27.25% of patients with clinically node-negative axilla. Conclusions In this retrospective study, ANN showed promising result as decision-supporting tools for estimating nodal disease. If prospectively validated, patients least likely to have nodal metastasis could be spared SLNB using predictive models. Trial registration Registered in the ISRCTN registry with study ID ISRCTN14341750. Date of registration 23/11/2018. Retrospectively registered. Electronic supplementary material The online version of this article (10.1186/s12885-019-5827-6) contains supplementary material, which is available to authorized users.
Published: 2019
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21. Rehabilitation of adult patients with severe-to-profound hearing impairment - why not cochlear implants?

Author: Per-Inge Carlsson, Sten Hellström, Margareta Edén, and Satu Turunen-Taheri
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Hearing loss, medicine.medical_treatment, Hearing Loss, Sensorineural, Population, Lower risk, Risk Assessment, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, Quality of life, Audiometry, medicine, Humans, Registries, Profound hearing impairment, 030223 otorhinolaryngology, education, Aged, Aged, 80 and over, Sweden, education.field_of_study, Rehabilitation, Chi-Square Distribution, Adult patients, business.industry, Hearing Tests, Age Factors, General Medicine, Middle Aged, Prognosis, Cochlear Implantation, Cochlear Implants, Logistic Models, Treatment Outcome, Otorhinolaryngology, 030220 oncology & carcinogenesis, Quality of Life, Female, medicine.symptom, business
Abstract: Background: In Sweden, an estimated prevalence of adult patients with severe-to-profound hearing loss is 0.2%, which corresponds to roughly 20,000. We know little about the use of cochlear implants (CIs) in this population and why not most of them are not offered CI. Objectives: To investigate the reasons for no rehabilitation with CI among this patient group. Materials and methods: Data were collected from 1076 patients in the Swedish Quality Register of Otorhinolaryngology. A baseline questionnaire and the reason for no CI, was evaluated. Results: Only 14.5% of the patients started a CI investigation, and 8.5% were rehabilitated with CI. Significantly more women (56.5%) than men received CI. The most common reasons for not receiving CI, were hearing reason (30.5%), indicating satisfaction with technical equipment, and unknown reason (25%). The oldest patient group (81-100 years old) had the highest risk for unknown reasons. Patients receiving extended audiological rehabilitation (53.5%) had a significantly lower risk for unknown reasons. Conclusions: It is worrying that the oldest patient group (81-100 years old) seemed to have fewer chances to start a CI investigation. An extended audiological rehabilitation increased the chances that professionals would discuss CI. Significance: This study shows that surprisingly few patients are offered CI despite their severe-to-profound hearing loss.
Published: 2019

22. Pituitary Metastases: A Nationwide Study on Current Characteristics With Special Reference to Breast Cancer

Author: Jeanette Wahlberg, Britt Edén Engström, Daniel S Olsson, Katarina Berinder, Per Dahlqvist, Margareta Nilsson, Fredrika Schill, Oskar Ragnarsson, Pia Burman, and Elisabet Englund
Subjects: Oncology, Adenoma, Adult, medicine.medical_specialty, Lung Neoplasms, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, MEDLINE, Breast Neoplasms, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Breast cancer, Internal medicine, medicine, Humans, Pituitary Neoplasms, Sweden, business.industry, Biochemistry (medical), Middle Aged, medicine.disease, 030220 oncology & carcinogenesis, Female, Presentation (obstetrics), business, 030217 neurology & neurosurgery
Abstract: To investigate the contemporary presentation of pituitary metastases.Thirty-eight patients diagnosed with pituitary metastases from 1996 to 2018 in Sweden.Pituitary metastases were confirmed by histopathology (n = 27) or considered highly likely according to radiological findings, including rapid tumor progression (n = 11). Medical records were reviewed and sellar images reexamined centrally.Breast and lung cancers were the most common primary tumors, in 45% and 21% of patients, respectively. Sixty-seven percent of breast cancers overexpressed human epidermal growth factor receptor 2 (HER2); 53% of pituitary metastases from breast cancers appeared ≥10 years after diagnosis of the primary tumor. At presentation, 71% appeared to have ACTH deficiency, 65% had TSH deficiency, and 26% had diabetes insipidus. Fatigue, nausea/vomiting, loss of appetite, weight loss, myalgia, and/or arthralgia were reported in 47% of patients with morning cortisol100 nmol/L vs 23% with cortisol ≥200 nmol/L. Sixteen patients had visual field defects, and eight had diplopia. Intrasellar and suprasellar tumor growth was the most frequent finding. Initially, a pituitary adenoma was considered the etiology in 18% of patients.Radiotherapy, pituitary surgery, and chemotherapy were used in 68%, 68%, and 11% of patients, respectively. One and 2 years after diagnosis of pituitary metastases, 50% and 26% of patients were alive.Pituitary metastases may be mistaken for pituitary adenomas and can appear late, especially in breast cancer. Breast cancers overexpressing HER2 seem prone to metastasize to the pituitary. Hypocortisolism may be misdiagnosed as cancer-related malaise. An increased awareness of pituitary metastases and undiagnosed pituitary failure can improve management in these patients.
Published: 2019

23. Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD-AF and treated with vitamin K antagonists

Author: Fitzmaurice, David A, Accetta, Gabriele, Haas, Sylvia, Kayani, Gloria, Lucas Luciardi, Hector, Misselwitz, Frank, Pieper, Karen, Ten Cate, Hugo, Turpie, Alexander G. G, Kakkar, Ajay K, Bassand, J. P. j, John Camm, A. j, Goldhaber, S. Z. j, Goto, S. j, Hacke, W. j, Mantovani, L. G. j, van Eickels, M. j, Verheugt, F. W. A. j, Fox, K. A. A. j, Gersh, B. J. j, Gibbs, H. j, Brodmann, M. j, Cools, F. j, Barretto, A. C. P. j, Connolly, S. J. j, Spyropoulos, A. j, Eikelboom, J. j, Corbalan, R. j, Hu, D. j, Jansky, P. j, Nielsen, J. D. j, Ragy, H. j, Raatikainen, P. j, Le Heuzey, J. Y. j, Darius, H. j, Keltai, M. j, Kakkar, S. j, Sawhney, J. P. S. j, Ambrosio, G. A. A. G. j, Koretsune, Y. j, Díaz, C. J. S. j, Atar, D. j, Stepinska, J. j, Panchenko, E. j, Lim, T. W. j, Jacobson, B. j, Oh, S. j, Viñolas, X. j, Rosenqvist, M. j, Steffel, J. j, Angchaisuksiri, P. j, Oto, A. j, Parkhomenko, A. j, Mahmeed, W. A. j, Hu, D. Y. j, Chen, K. N. j, Zhao, Y. S. j, Zhang, H. Q. j, Chen, J. Z. j, Cao, S. P. j, Wang, D. W. j, Yang, Y. J. j, Li, W. H. j, Yin, Y. H. j, Tao, G. Z. j, Yang, P. j, Chen, Y. M. j, He, S. H. j, Wang, Y. j, Wang, Y. j, Fu, G. S. j, Li, X. j, Wu, T. G. j, Cheng, X. S. j, Yan, X. W. j, Zhao, R. P. j, Chen, M. S. j, Xiong, L. G. j, Chen, P. j, Jiao, Y. j, Guo, Y. j, Xue, L. j, Wang, F. Z. j, Li, H. j, Yang, Z. M. j, Bai, C. L. j, Chen, J. j, Chen, J. Y. j, Chen, X. j, Feng, S. j, Fu, Q. H. j, Gao, X. J. j, Guo, W. N. j, He, R. H. j, He, X. A. j, Hu, X. S. j, Huang, X. F. j, Li, B. j, Li, J. j, Li, L. j, Li, Y. H. j, Liu, T. T. j, Liu, W. L. j, Liu, Y. Y. j, Lu, Z. C. j, Luo, X. L. j, Ma, T. Y. j, Peng, J. Q. j, Sheng, X. j, Shi, X. J. j, Sun, Y. H. j, Tian, G. j, Wang, K. j, Wang, L. j, Wu, R. N. j, Xie, Q. j, Xu, R. Y. j, Yang, J. S. j, Yang, L. L. j, Yang, Q. j, Yang, Y. J. j, Ye, Y. j, Yu, H. Y. j, Yu, J. H. j, Yu, T. j, Zhai, H. j, Zhan, Q. j, Zhang, G. S. j, Zhang, R. j, Zhang, Y. j, Zheng, W. Y. j, Zhou, B. j, Zhou, Z. H. j, Zhu, X. Y. j, Kakkar, J. P. S. j, Jadhav, P. j, Durgaprasad, R. j, Ravi Shankar, A. G. j, Rajput, R. K. j, Bhargava, K. j, Sarma, R. j, Srinivas, A. j, Roy, D. j, Nagamalesh, U. M. j, Chopda, M. j, Kishore, R. j, Kulkarni, G. j, Chandwani, P. j, Pothiwala, R. A. j, Padinhare Purayil, M. j, Shah, S. j, Chawla, K. j, Kothiwale, V. A. j, Raghuraman, B. j, Vijayaraghavan, G. j, Vijan, V. M. j, Bantwal, G. j, Bisne, V. j, Khan, A. j, Gupta, J. B. j, Kumar, S. j, Jain, D. j, Abraham, S. j, Adak, D. j, Barai, A. j, Begum, H. j, Bhattacharjee, P. j, Dargude, M. j, Davies, D. j, Deshpande, B. j, Dhakrao, P. j, Dhyani, V. j, Duhan, S. j, Earath, M. j, Ganatra, A. j, Giradkar, V. j, Karthikeyan, R. j, Kasala, L. j, Kaur, S. j, Krishnappa, S. j, Lawande, A. j, Lokesh, B. j, Madarkar, N. j, Meena, R. j, More, P. j, Naik, D. j, Prashanth, K. j, Rao, M. j, Rao, N. M. j, Sadhu, N. j, Shah, D. j, Sharma, M. j, Shiva, P. j, Singhal, S. j, Suresh, S. j, Vanajakshamma, V. j, Panse, S. 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(Susumu) Suzuki S., Suzuki, Y., Tada, M., Taguchi, A., Takagi, T., Takagi, Y., Takahashi, K., Takahashi, S., Takai, H., Takanaka, C., Take, S., Takeda, H., Takei, K., Takenaka, K., Tana, T., Tanabe, G., Taya, K., Teragawa, H., Tohyo, S., Toru, S., Tsuchiya, Y., Tsuji, T., Tsuzaki, K., Uchiyama, H., Ueda, O., Ueyama, Y., Wakaki, N., Wakiyama, T., Washizuka, T., Watanabe, M., Yamada, T., Yamagishi, T., Yamaguchi, H. (Kenichi) Yamamoto K. (Kentaro) Yamamoto K. (Kunihiko) Yamamoto K., Yamamoto, T., Yamaura, M., Yamazoe, M., Yasui, K., Yokoyama, Y., Yoshida, K., Ching, C. K., Foo, C. G., Chow, J. H., Chen, D. D., Jaufeerally, F. R., Lee, Y. M., Lim, G., Lim, W. T., Thng, S., Yap, S. Y., Yeo, C., Pak, H. N., Kim, J. -B., Kim, J. H., Jang, S. -W., Kim, D. H., Ryu, D. R., Park, S. W., Kim, D. -K., Choi, D. J., Oh, Y. S., Cho, M. -C., Kim, S. -H., Jeon, H. -K., Shin, D. -G., Park, J. S., Park, H. K., Han, S. -J., Sung, J. H., Cho, J. -G., Nam, G. -B., On, Y. K., Lim, H. E., Kwak, J. J., Cha, T. -J., Hong, T. J., Park, S. H., Yoon, J. H., Kim, N. -H., Kim, K. -S., Jung, B. C., Hwang, S., Kim, C. -J., Kim, D. B., Ahn, J. J., An, H. J., Bae, H., Baek, A. L., Chi, W. J., Choi, E. A., Choi, E. H., Choi, H. K., Choi, H. S., Han, S., Heo, E. S., Her, K. O., Hwang, S. W., Jang, E. M., Jang, H. -S., Jang, S., Jeon, H. -G., Jeon, S. R., Jeon, Y. R., Jeong, H. K., Jung, I. -A. (Hyeon Jeong) Kim H. J. (Hyun Ju) Kim H. J. (Ji Seon) Kim J. S. (Jung Sook) Kim J. S., Kim, J. A., Kim, K. T., Kim, M. S. (Sang Hee) Kim S. H. (Sang Hyun) Kim S. H., Kim, Y. -I., Lee, C. S., Lee, E. H., Lee, G. H., Lee, H. Y., Lee, K. H., Lee, K. R., Lee, M. S., Lee, M. -Y., Lee, R. W., Lee, S. E., Lee, S. H., Lee, S., Lee, W. Y., Park, A. R., Park, B. R., Park, H. N., Park, J. H., Park, M., Park, Y., Seo, S. -Y., Shim, J., Sim, J. H., Sohn, Y. M., Son, W. S., Son, Y. S., Song, H. J., Wi, H. K., Woo, J. J., Ye, S., Yim, K. H., Yoo, K. M., Yoon, E. J., Yun, S. Y., Chawanadelert, S., Mongkolwongroj, P., Kanokphatcharakun, K., Cheewatanakornkul, S., Laksomya, T., Pattanaprichakul, S., Chantrarat, T., Rungaramsin, S., Silaruks, S., Wongcharoen, W., Siriwattana, K., Likittanasombat, K., Katekangplu, P., Boonyapisit, W., Cholsaringkarl, D., Chatlaong, B., Chattranukulchai, P., Santanakorn, Y., Hutayanon, P., Khunrong, P., Bunyapipat, T., Jai-Aue, S., Kaewsuwanna, P., Bamungpong, P., Gunaparn, S., Hongsuppinyo, S., Inphontan, R., Khattaroek, R., Khunkong, K., Kitmapawanont, U., Kongsin, C., Naratreekoon, B., Ninwaranon, S., Phangyota, J., Phrommintikul, A., Phunpinyosak, P., Pongmorakot, K., Poomiphol, S., Pornnimitthum, N., Pumprueg, S., Ratchasikaew, S., Sanit, K., Sawanyawisuth, K., Silaruks, B., Sirichai, R., Sriwichian, A., Suebjaksing, W., Sukklad, P., Suttana, T., Tangsirira, A., Thangpet, O., Tiyanon, W., Vorasettakarnkij, Y., Wisaratapong, T., Wongtheptien, W., Wutthimanop, A., Yawila, S., Altun, A., Ozdogru, I., Ozdemir, K., Yilmaz, O., Aydinlar, A., Yilmaz, M. B., Yeter, E., Ongen, Z., Cayli, M., Pekdemir, H., Ozdemir, M., Sucu, M., Sayin, T., Demir, M., Yorgun, H., Ersanli, M., Okuyan, E., Aras, D., Abdelrahman, H., Aktas, O., Alpay, D., Aras, F., Bireciklioglu, M. F., Budeyri, S., Buyukpapuc, M., Caliskan, S., Esen, M., Felekoglu, M. A., Genc, D., Ikitimur, B., Karaayvaz, E. B., Kilic Karatas, S., Okutucu, S., Ozcelik, E., Quisi, A., Sag, H., Sahiner, L., Sayin, B. Y., Seker, T., Uzun Alkan, D., Yildirim, E., Yildirim, R., Yilmaz, F., Yuksekdag, V., Vensentini, N., Ingaramo, A. C., Sambadaro, G. A., Fernandez Caputi, V., Berman, S. G., Dragotto, P., Kleiban, A. J., Centurion, N., Giacomi, G., Ahuad Guerrero, R. A., Conde, D., Zapata, G., Di Paola, L. A., Ramos, J. L., Dran, R. D., Egido, J., Fernandez, A. A., Fosco, M. J., Sassone, S., Sinisi, V. A., Cartasegna, L. R., Berli, M. A., Gomez Vilamajo, O. A., Ferroni, F., Alaguibe, E. D., Alvarez D'Amelio, A., Arabetti, C., Arias, L., Belardi, J. A., Bergesio, L., Berli, F., Berli, M., Borchowiec, S., Buzzetti, C., Cabrini, R., Campisi, V., Cappi, A. L., Carrizo, R., Colombo Berra, F., Costabel, J. P., Costamagna, O. J. A., Damonte, A. A., De Urquiza, I. N., Diez, F., Eden, M. F., Fanuele, M., Fernandez Voena, F., Foa Torres, M., Funosas, C., Giacomi, M. P., Gimenez, C. H., Gurfinkel, E. P., De, L. M. Had M., Hansen, V., Hrabar, A. D., Ingratta, M., Lopez, A., Maehara, G., Maffei, L., Martinelli, A., Martinelli, C., Matkovich, J., Mautner, B., Meirino, A., Munguia, R., Navarro, A., Novas, V., Perez Prados, G., Pontoriero, J., Potito, R. N., Ricotti, C., Rodriguez, M. A., Rolandi, F., Said Palladino, M. E., Salinger, M., Sanziani, L. S., Schygiel, P. O., Sossich, A., Tinto, J. F., Tonelli, L., Tufare, A. L., Vallejo, M., Yunis, M. E., Zillo, M., Zurbrigk, F. J., Sobral Filho, D. C., Jaber, J., Armaganijan, D., Faria Neto, J., Steffens, A., de Souza, W. K. S. B., de Souza Neto, J. D., Ribeiro, J. M., Silveira Teixeira, M., Ferreira Rossi, P. R., Pires, L., Moreira, D., Moura Jorge, J. C., Menezes Lorga Filho, A., Bodanese, L. C., Westerlund Montera, M., Del Carlo, C. H., Da Rocha Rodrigues, T., Alves da Costa, F. A., Lopes, A., Lopes, R., Araujo, G. R., Fernandes Manenti, E. R., Kerr Saraiva, J. F., Ferreira Braga, J. C., Negri, A., Souto, L., Moncada, C., Bertolim Precoma, D., Roquette, F., Reis, G., Ramos Filho, R. A., Lanna Figueiredo, E., Vieira Botelho, R., Munhoz da Fontoura Tavares, C., Costantini Frack, C. R., Abdalla Saad, J., Finimundi, H. C., Pisani, C., Chemello, D., Pereira Martins, M., Broilo Franca, C. C., Alban, F., Aranha Rosito, G. B., de Moura Xavier Moraes, J. B., Tumelero, R. T., Nigro Maia, L., de Almeida, R. S., do Carmo Borges, N. C., Gomes Ferreira, L. G., Agliardi, P., de Oliveira Gomes, J. A., Araujo, V., Nakazone, M. A., Barbosa, T., Barroso, S., Belisario Falchetto, E., Bellotti Lopes, H., Benez Teixeira Lemos, M. A., Biazus, G., Borges Queiroz, L., Camazzola, F. E., Caporale, M., Cardoso Boscato, S., Chieza, F., Chokr, M. O., Clemente Mingireanov, R., Codonho Goes, N., Correa, C., Costa, M., Costantini Ortiz, C., da Silva, L. S., da Silva Paulitsch, F., da Silveira, J. A., Daros, E., de Araujo, G. R., Del Monaco, M. I., Dias, C., Dias, M. A., Drummond Wainstein, A. P., Ely Pizzato, P., Esteves, D. C., Fabri, P., Felix Lorenzato Fonseca, T., Fernandes, E., Fonseca, C., Frack Costantini, C. R., Franchin Ferraz, R., Freire, F., Gottardo, P., Guanaes, D., Guizzardi, S., Hettwer Magedanz, E., Igansi, F., Jannuzzi, F., Junior, G., Komar, D., Lino, E. G., Lopes, D., Lourenco da Silva Junior, O., Lustosa, E., Macagnan, A. P., Marinho, M. C., Mazzoni, M., Melo, G., Mortari, L., Mouco, O. M. C. C., Nanzer Vital, C., Ormundo, C., Oss Emmer, S., Palmegiani, E., Pavani, R., Pereira, L., Pereira, V. L., Perreira, R., Poletti, S., Quaia Fortunato, S. C., Queirantes, C., Ramos Pereira, N., Rech, R. L., Ribeiro, S., Rodrigues, A., Roesch, H., Ruaro Reichert, T., Santos, D., Santos, I., Santos, M., Seroqui, M. V., Silva, S., Soares, L., Spolaor, L., Stoll, C., Toazza Duda, N., Trama, L., Unterkircher, B., Valois, M. V., Vargas, T., Viana, T., Vicente, C., Vidal Armaganijan, L., Vieira Homem, R., Vieira Torres, L. G., Vila Boas, L., Villaca Guimaraes Filho, F., Eggers, G., Bugueno Gutierrez, C., Arriagada, G., Potthoff Cardenas, S., Stockins Fernandez, B. A. J., Conejeros, C., Houzvic, C., Marin Cuevas, P., Montecinos, H., Forero, A., Lanas, F., Larico Gomez, M., Charme Vilches, G., Rey, C., Astudillo, C., Aguilar, J., Campisto, Y., Lara, C., Molina, E., Munoz Oyarzon, J., Olguin, V., Vergara, M., Villan, C., Sanchez Diaz, C. J., Illescas Diaz, J., Leal Cantu, R., Ramos Zavala, M. G., Cabrera Jardines, R., Espinola Zavaleta, N., Villarreal Umana, S., Lopez Rosas, E., Llamas Esperon, G., Pozas, G., Cardona Munoz, E., Matadamas Hernandez, N., Leyva Rendon, A., Garcia Hernandez, N., de los Rios Ibarra, M., Virgen Carrillo, L., Lopez Villezca, D., Hernandez Herrera, C., Lopez Prieto, J. J., Gaona Rodriguez, R., Villeda Espinosa, E., Flores Martinez, D., Velasco Barcena, J., Yong, R., Rodriguez Briones, I., Leiva Pons, J. L., Alvarez Lopez, H., Olvera Ruiz, R., de la Vega, C. D., Cantu Brito, C., Chuquiure Valenzuela, E., Reyes-Sanchez, R., Nandayapa Flores, O., Benavides Gonzalez, M., Arriaga Nava, R., Morales Cerda, J. D., Fierro Fierro, O., Fajardo Campos, P., Alfaro, T. A. A., Altamirano Bellorin, S., Avena, R., Chavarria, M., Espinosa, I., Flores Silva, F., Garcia Nava, R. H., Godoy, K., Gonzalez Felix, E. J., Gonzalez Garcia, C. L., Gonzalez Salas, L. G., Guajardo, P., Hernandez Gonzalez, S., Izquierdo, T., Mancilla Ortiz, M. C., Martinez Vasquez, D., Mendoza, N., Morales, J., Nikitina, N., Ochoa Aybar, S., Ortiz, A., Padilla Macias, P., Perez, F., Perez Sanchez, J. A., Pina Toledano, S., Ramos Gonzalez, M., Rivera Ramos, C., Roa Castro, V., Romero Cardona, G., Ruiz Cornejo, M., Salinas, A., Santana, G., Sida Perez, P., Tovar Castaneda, A. C., Trujillo Cortes, R., Lenz, K., Drexel, H., Foechterle, J., Hagn, C., Podczeck-Schweighofer, A., Huber, K., Winkler, M., Schneeweiss, B., Gegenhuber, A., Lang, W., Eichinger-Hasenauer, S., Kaserer, P., Sykora, J., Rasch, H., Pichler, M., Schaflinger, E., Strohmer, B., Breier, R., Ebner, K. -M., Eischer, L., Freihoff, F., Lischka-Lindner, A., Mark, T., Mirtl, A., Said, A., Stocklocker, C., Vogel, B., Vonbank, A., Wohrer, C., Zanolin, D., Paparella, G., Vandergoten, P., Parque, J. -L., Capiau, L., Vervoort, G., Wollaert, B., Desfontaines, P., Mairesse, G., Boussy, T., Godart, P., De Wolf, A., Voet, J., Heyse, A., Hollanders, G., Anne, W., Vercammen, J., Purnode, P., Blankoff, I., Faes, D., Balthazar, Y., Beutels, M., Marechal, P., Verstraete, S., Xhaet, O., Striekwold, H., Thoeng, J., Hermans, K., Alzand, B., Ascoop, A. -K., Banaeian, F., Barbuto, A. -M., Billiaux, A. C., Blockmans, M., Bouvy, C., Brike, C., Capiau, H., Casier, T., Conde Y Bolado, A., De Cleen, D., De Coninck, M., de Vos, M., de Weerdt, N., Delforge, M., Delvigne, M., Denie, D., Derycker, K., Deweerd, E., Dormal, F., Drieghe, S., Everaert, M., Eykerman, T., Feys, E., Ghekiere, M., Gits, F., Hellemans, S., Helvasto, L., Jacobs, C., Lips, S., Mestdagh, I., Nimmegeers, J., Piamonte, V., Pollet, P., Postolache, A., Raepers, M., Raymenants, E., Richa, J., Rombouts, H., Salembier, J., Scheurwegs, C., Semeraro, O., Simons, N., Smessaert, C., Smolders, W., Stockman, I., Tahon, S., Thyssen, V., Tincani, G., Van Durme, F., Van Lier, D., Vandekerckhove, H., Vandekerckhove, Y., Vandenbroeck, D., Vandorpe, A., Vanhalst, E., Vanhauwaert, B., Vantomme, C., Vergauwen, L., Verloove, H., Vydt, T., Weyn, T., Reichert, P., Spacek, R., Machova, V., Zidkova, E., Ludka, O., Olsr, J., Kotik, L., Plocova, K., Racz, B., Ferkl, R., Hubac, J., Kotik, I., Monhart, Z., Burianova, H., Jerabek, O., Pisova, J., Petrova, I., Dedek, V., Honkova, M., Podrazil, P., Spinar, J., Vitovec, J., Novak, M., Lastuvka, J., Durdil, V., Antonova, P., Bockova, L., Bultas, J., Chlumsky, J., Dastychova, L., Drasnar, T., Honek, J., Horejsi, M., Hubacova, V., Janska, L., Kopeckova, I., Kratochvilova, R., Krcova, E., Labrova, R., Lindourkova, A., Lipoldova, J., Lubanda, H., Ludkova, A., Mahdalikova, L., Majernikova, M., Michalik, D., Potuznik, P., Prochazkova, E., Sulc, A., Sveceny, J., Valtova, M., Zidek, M., Zika, J., Nielsen, J., Nielsen, H., Husted, S., Hintze, U., Rasmussen, S., Bremmelgaard, A., Markenvard, J., Boerger, J., Solgaard, J., Simonsen, P., Loekkegaard, T., Bruun, M., Mertz, J., Dominguez, H., Skagen, K., Egstrup, K., Ibsen, H., Raymond, I., Bang-Hansen, T., Ellervik, C., Eriksen, E., Jensen, L., Jensen, M., Leth, M., Nygaard, A., Park, J., Schou, M., Therkelsen, A., Tilma, J., Vesterager, K., Airaksinen, J., Arola, O., Koistinen, J., Nappila, H., Peltomaki, K., Rasanen, V., Vasankari, T., Galinier, M., Gottwalles, Y., Paganelli, F., Loiselet, P., Muller, J. -J., Koujan, M. B., Marquand, A., Destrac, S., Piot, O., Delarche, N., Cebron, J. -P., Boveda, S., Guenoun, M., Guedj-Meynier, D., Galley, D., Ohayon, J., Assouline, S., Zuber, M., Amarenco, P., Ellie, E., Kadouch, J., Fournier, P. -Y., Huberman, J. -P., Lemaire, M., Rodier, G., Milandre, L., Vandamme, X., Sibon, I., Neau, J. -P., Mahagne, M. H., Mielot, A., Bonnefoy, M., Churet, J. -B., Navarre, V., Sellem, F., Monniot, G., Boyes, J. -P., Doucet, B., Martelet, M., Obadia, D., Crousillat, B., Mouallem, J., Bearez, E., Nazeyrollas, P., Brugnaux, J. P., Fedorowsky, A., Casassus, F., Berneau, J. -B., Chemin, F., Falvo, N., Perron, J. -M., Poulard, J. -E., Barreau, A., Beltra, C., Corrihons, E., Decarsin, N., Dubois, B., Ducasse, E., Giry, X., Kemmel, A., Ledure, S., Lemaire, N., Robin, F., Rosolin, N., Sanchez, D., Suissa, A., Koniger, G., Purr, J., Gerbaulet, U., Kellner, B. -T., Kopf, A., Schafer, T., Zauzig, H., Riegel, P., Hohensee, H., Eissfeller, E., Eder, W., Rehling, G., Glatzel, D., Zutz, S., Heinz, G. -U., Menke, H., Pustelnik, A., Sandow, P., Ludwig, N., Wiswedel, H., Wildenauer, W., Axthelm, C., Schwarz, T., Babyesiza, A., Stuchlik, G., Zimny, H. -H., Kropp, M., Kahl, F., Caspar, A., Omankowsky, S., Lassig, T., Hartmann, H. -J., Lehmann, G., Bindig, H. -W., Hergdt, G., Reimer, D., Hauk, J., Dorsch, W., Dshabrailov, J., Michel, H., Rapp, K. -A., Vormann, R., Mayer, P., Horstmeier, U., Eissing, V., Hey, H., Leuchtgens, H., Lilienweiss, V., Kolitsch, K., Schubert, C., Lauer, H., Buchner, T., Brauer, G., Kamin, S., Muller, K., Abdel-Qader, M., Baumbach, S., Ebert, H. -H., Schwencke, C., Schellong, S., Bernhardt, P., Karolyi, L., Sievers, B., Haverkamp, W., Salbach, P., Rohnisch, J. -U., Schoen, S., Erdle, W., Mueller, T., Mueller, H., Mitrovic, V., Babjakova, Z., Bergner, K., Boehme, S., Bonin, K., Buckert, D., Busch, F., Dichristin, U., Diez, S., Fleck, A., Flint, K., Floegel, H., Fritz, C., Frommhold, R., Gehre, J., Geyer, J., Grytzmann, A., Hahn, M., Helgert, K., Hubert, K., Kirchner-Volker, K., Klein, V., Kroll, D., Krueger, A., Lehmann, R., Mann, L., Maselli, A., Menken, G., Mikes, K., Mortan, H., Nasser, N., Nicolaus, D., Plauskat, A., Pomper, L., Quietzsch, A., Ravenhorst, C., Reichelt, C., Reimer, C., Schaefer, B., Scharrer, S., Schirmer, K., Schmidt, K., Schoene, R., Schulze, J., Schuppe, M., Simon, S., Sommer, S., Spranger, K., Talkenberger, A., Tauber, K., Tetlak, A., Toennishoff, T., Voelkel-Babyesiza, R., Voigts, B., Weiser, U., Wesendorf, S., Wildenauer, S., Wolf, T., Wurziger, J., Zak, J., Zauzig, H. -D., Ziefle, S., Zincke, S., Vangel, S., Szalai, G., Merkely, B., Kancz, S., Boda, Z., Nagy, A., Laszlo, Z., Matoltsy, A., Gaszner, B., Polgar, P., Habon, T., Noori, E., Juhasz, G., Kanakaridisz, N., Szentpeteri, I., Juhasz, F., Vertes, A., Papp, A., May, Z., Ferenczi, J., Egyutt, M., Kis, E., Engelthaler, G., Szantai, G., Fulop, E., Gombos, P., Gulyas, D., Jen, P., Kiralyhazine Gyorke, E., Kovacs, M., Kovacsne Levang, S., Marianna, S., Radics, Z., Sydo, N., Szalo, R., Szilagyi, A., Sztanyik, F., Vandrus, B., Agnelli, G., Ambrosio, G., Tiraferri, E., Santoro, R., Testa, S., Di Minno, G., Moia, M., Caimi, T. M., Martini, G., Tessitori, M., Cappelli, R., Poli, D., Quintavalla, R., Melone, F., Cosmi, F., Pizzini, A., Piseddu, G., Fanelli, R., Latella, C., Santi, R., Pancaldi, L., De Cristofaro, R., Palareti, G., De Blasio, A., Salerno Uriarte, J., Minetti, F., Pogliani, E. M., Lonati, L. M., Accogli, M., Ciampani, N., Malengo, S., Feola, M., Raisaro, A., Fattore, L., Grilli, P., Germini, F., Settimi, M., Alunni, M., Duranti, G., Tedeschi, L., Baglioni, G., Avanzino, G., Berardi, M., Pannacci, V., Giombolini, A., Nicoli, S., Scarponi, T., Allasia, B., Ricciarini, P., Nasorri, R., Argena, A., Bossolasco, P., Ronchini, P., Filippi, A., Tradati, F., Bulla, C., Donzelli, L., Foppa, L., Bottarelli, M. L., Tomasello, A., Mauric, A., Femiano, C., Reggio, R., Lillo, F., Mariani, A., Forcignano, F., Volpe, M., D'Avino, M., Bongiorni, M. G., Severi, S., Capucci, A., Lodigiani, C., Salomone, E., Serviddio, G., Tondo, C., Golino, P., Mazzone, C., Iacopino, S., Pengo, V., Galvani, M., Moretti, L., Ambrosino, P., Banfi, E., Biagioli, V., Bianchi, A., Boggian, G., Breschi, M., Brusorio, S., Calcagnoli, F., Campagna, G., Carpenedo, M., Ciabatta, C., Ciliberti, G., Cimmino, G., D'Arienzo, C., Di Gennaro, L., Fedele, M., Ferrini, P. M., Granzow, K., Guazzaloca, G., Guerra, F., Lo Buglio, A., Longo, S., Macellari, F., Mesolella, E., Mollica Poeta, E., Occhilupo, P., Oriana, V., Rangel, G., Salomone, L., Scaccianoce, A., Scarone, C., Segreti, L., Sottilota, G., Villani, R., Zecca, C., Ruiter, J. H., Klomps, H., Bongaerts, M., Pieterse, M. G. C., Guldener, C., Herrman, J. -P., Lochorn, G., Lucassen, A., Adriaansen, H., The, S. H. K., Nierop, P. R., Hoogslag, P. A. M., Hermans, W., Groenemeijer, B. E., Terpstra, W., Buiks, C., Boersma, L. V. A., Boersma-Slootweg, M., Bosman, F., Bosschaert, M., Bruin, S., Danse, I., De Graaf, J., de Graauw, J., Debordes, M., Dols, S., Geerlings, F., Gorrebeeck, K., Jerzewski, A., Jetten, W., Kelderman, M., Kloosterman, T., Koomen, E. M., Krikken, J., Melman, P., Mulder, R., Pronk, A., de Vos, A. S., te Kaat, J., Tonino, P., Uppelschoten, B., van de Loo, R., van der Kley, T., van Leeuwen, G., van Putten, J. J., Westerman, L., Berge, E., Sirnes, P. A., Gjertsen, E., Hole, T., Erga, K., Hallaraker, A., Skjelvan, G., Ostrem, A., Ghezai, B., Svilaas, A., Christersson, P., Oien, T., Hoegh Henrichsen, S., Berg-Johansen, J., Otterstad, J. E., Antonsen, H., Ausen, K., Claussen, H., Dominguez, I., Jekthammer, A., Lensebraaten, A. B., Nilsen, V., O'Donovan, M., Ringdalen, K., Strand, S., Korzeniak, R., Gieroba, A., Biedrzycka, M. (Marcin) Ogorek M., Wozakowska-Kaplon, B., Loboz-Grudzien, K., Kosior, J., Supinski, W., Kuzniar, J., Zaluska, R., Hiczkiewicz, J., Swiatkowska-Byczynska, L., Kucharski, L., Gruchala, M., Minc, P., Olszewski, M., Kania, G., Krzciuk, M., Lajkowski, Z., Ostrowska-Pomian, B., Lewczuk, J., Zinka, E., Karczmarczyk, A., Chmielnicka-Pruszczynska, M., Trusz-Gluza, M., Opolski, G., Bronisz, M. (Michal) Ogorek M., Glanowska, G., Ruszkowski, P., Jaworska, K., Sciborski, R., Okopien, B., Kukla, P., Wozniak-Skowerska, I., Galbas, K., Cymerman, K., Jurowiecki, J., Miekus, P., Myszka, W., Mazur, S., Lysek, R., Baszak, J., Rusicka-Piekarz, T., Raczak, G., Domanska, E., Nessler, J., Lesnik, J., Ambicka, M., Andrzejewski, D., Araminowicz, J., Barszcz, A., Bartkowiak, R., Bartnik, J., Basiak, M., Bekieszczuk, E., Bernat, L., Biedrzycki, L., Biernacka, A., Blaszczyk, D., Broton, E., Brzozowski, W., Brzustowska, M., Bzymek, R., Chmielowski, A., Chojnowski, P., Cichomski, R., Cieslak, K., Cieszynska, A., Curyllo, B., Czamara, M., Danilowicz-Szymanowicz, L., Dolecka, B., Drelich, L., Dudzik-Richter, B., Dybala, T., Dziuba, M., Faron, W., Figura-Chmielewska, M., Frankiewicz, A., Gadzinski, W., Gasior, E., Gosciniecka, B., Gutknecht, P., Guziewicz, M., Jackun-Podlesna, A., Jaguszewska, G., Jankielewicz, J., Jaremczuk-Kaczmarczyk, A., Jargiello-Baszak, M., Jarzebowski, A., Jaskulska-Niedziela, E., Jaworska-Drozdowska, M., Kabat, J., Kaczmarzyk-Radka, A., Kalin, K., Kaliszczak, R., Kiliszek, M., Klata, M., Kluczewski, M., Kobielusz-Gembala, I., Kochanska, E., Kociolek, D., Kolodzinska, A., Komlo, A., Konopka, A., Korczowska, E., Kowal, E., Kowalczyk, H. K., Kremis, E., Kruczyk, D., Krzesiak-Lodyga, A., Krzyzanowski, M., Kurdzielewicz, W., Kustrzycka-Kratochwil, D., Lesniewska-Krynska, D., Leszczynski, J., Lewicka, E., Lichota, E., Lip, K., Loboz-Rudnicka, M., Luka, J., Lysek-Jozefowicz, A., Machnikowska, M., Majewska, K., Mariankowski, R., Markiewicz, A., Mazur, M., Metzgier-Gumiela, A., Miedlar, E., Mielcarek, M., Neubauer-Geryk, J., Niedek, J., Niemirycz-Makurat, A., Nowak, A., Nowak, S., Opielowska-Nowak, B., Ozgowicz, M., Pawelska-Buczen, A., Pawlik-Rak, E., Piotrowicz, R., Ptaszynski, P., Raczynska, A., Rogowski, W., Romanek, J., Romaszkiewicz, R., Rostoff, P., Roszczyk, N., Rozewska-Furmanek, D., Rychta, J., Rzyczkowska, B., Sidor, A., Skalska, J., Smichura, M., Splawski, M., Staneta, P., Staniszewska, E., Starak-Marciniak, J., Stopyra-Poczatek, M., Sukiennik-Kujawa, M., Szafranski, J., Szalecki, P., Szczepanska, A., Szkrobka, W., Szuchnik, E., Szulowska, A., Szumczyk-Muszytowska, G., Szwoch, M., Traczyk, T., Troszczynska, M., Trzcinski, G., Tybura, S., Walasik, P., Wegrzynowska, M., Wesolowska, K., Wieczorek, W., Wierzbicka, A., Wilczewski, P., Wilgat-Szecowka, M., Wojewoda, P., Wojnowski, L., Wrobel, M., Zakutynska-Kowalczyk, K., Zyczynska-Szmon, M., Eltishcheva, V., Libis, R., Tereshchenko, S., Popov, S., Belenky, D., Zateyshchikova, A., Kropacheva, E., Kolesnikova, A., Nikolaev, K., Egorova, L., Khokhlov, A., Yakupov, E., Poltavskaya, M., Zateyshchikov, D., Drapkina, O., Vishnevsky, A., Barbarash, O., Miller, O., Aleksandrova, E., Chizhov, P., Sergeev, M., Shutemova, E., Mazur, E., Zrazhevskiy, K., Novikova, T., Kostenko, V., Moiseeva, Y., Polkanova, E., Sobolev, K., Rossovskaya, M., Zubeeva, G., Shapovalova, Y., Nagibovich, O., Edin, A., Agakhanyan, A., Batalov, R., Belenkova, Y., Bitakova, F., Chugunnaya, S., Dumikyan, A., Erofeeva, S., Gorbunova, E., Gorshkova, T., Gubanov, A., Gurmach, M., Ivanova, Y., Kolesova, T., Konyushenko, D., Korneeva, O., Kropova, O., Kuchuk, P., Kungurtseva, O., Kupriyanova, T., Kurylo, B., Kuvanova, M., Lebedeva, O., Lileeva, E., Machilskaya, O., Medvedeva, T., Monako, G., Motylev, I., Nagibovich, G., Novikova, E., Orlov, Y., Osmolovskaya, Y., Ovsannikova, A., Platonov, D., Rachkova, S., Sinitsina, O., Speshilova, S., Suslova, O., Ushakov, A., Volodicheva, O., Zemlianskaia, O., Zhirov, I., Zhuravleva, E., Zotova, I., Alvarez Garcia, P., Lopez Fernandez, M. F., Tercedor, L., Tranche Iparraguirre, S., Toran Monserrat, P., Marquez Contreras, E., Isart Rafecas, J., Motero Carrasco, J., Garcia Pavia, P., Gomez Pajuelo, C., Moro Serrano, C., Iglesias Alonso, L. F., Grande Ruiz, A., Merce Klein, J., Gonzalez Juanatey, J. R., Baron Esquivias, G., Monte Collado, I., Palacin Piquero, H., Brotons Cuixart, C., Rodriguez Morato, M., Bayo I Llibre, J., Corros Vicente, C., Vida Gutierrez, M., Epelde Gonzalo, F., Almeida Fernandez, C. A., Del Val Plana, N., Escriva Montserrat, E., Montero Alia, J. J., Barreda Gonzalez, M., Moleiro Oliva, M. A., Iglesias Sanmartin, J., Jimenez Gonzalez, M., Rodriguezálvarez, M., Herreros Melenchon, J., Ripoll Vera, T., Ridocci Soriano, F., Garcia Riesco, L., Marco Macian, M. D., Quiles Granado, J., Jimenez Navarro, M., Cosin Sales, J., Vaquer Perez, J. V., Vazquez Caamano, M., Arcocha Torres, M. F., Marcos Gomez, G., Iniguez Romo, A., Prieto Diaz, M. A. (Carmela) Alonso C. (Concepcion) Alonso C., Alvarez, D., Alvarez, M., Amaro, M., Andere, N., Aracil Villar, J., Armitano Ochoa, R., Austria, A., Barbeira, S., Barraquer Feu, E., Bartes, A., Becerra Munoz, V., Bermudez Jimenez, F. J., Branjovich Tijuan, A., Cabeza Ramirez, J., Cabrera Ramos, M., Calvo Martinez, E., Campo Moreno, M., Cancho Corchado, G., Casanova Gil, M., Castillo Orive, M., Castro Fernandez, D., Cebollada del Misterio, M., Codinachs Alsina, R., Cortada Cabrera, A., de Faria, J. C. P. P., Costas, S., Cotilla Marco, M. I., Dachs, M., Diaz Lopez, C. M., Domenech Borras, A., Elorriaga Madariaga, A., Espallargas, A., Fernandez, M., Fernandez Escobar, E., Fernandez Mas, E., Ferrer, A., Fosch, J., Garcia Bermudez, M., Garcia Millan, V., Gavira Saenz, M., Gines Garcia, C., Gomez, C., Gomez Perez, Y., Gonzales Segovia, A., Gonzalez, P., Grigorian, L., Guerrero Molina, A., Del, C. Gutierrez del Val M., Herrero Maeso, B., Hevia Rodriguez, E., Iglesias Garcia, A., Jimenez Fernandez, M. J., Jimeno Besa, B., Juan Salvadores, P., Lage Bouzamayor, M. B., Lasuncion, I., Lezcano Gort, L. E., Llobet Molina, M., Lopez, M., Manzanal Rey, A., Mara Guerra, J., Marcus, S., Martin Vila, A., Martinez Mena, M., Mazon, P., Mendez Zurita, F., Millan, G., Molina, M., Montero Alia, P., Montes, D., Moure Gonzalez, M., Munoz Munoz, R. B., Negrete Palma, A., Orellana Figueroa, H. N., Ortega, V. M., Ortiz Cortes, C., Otero Tomera, D., Palomo Merchan, N., Pareja Ibar, I., Pena Garcia, E., Pereda Armayor, M., Perez Carasa, M., Prieto, I., Quintern, V., Renom, R., Rincon Diaz, L. M., Rios, V., Riquelme Sola, L., Rivera, R., Robiro Robiro, X., Roca, M., Roca Saumell, C., Rodrigo, C., Rodriguez, E., Rodriguez Garcia, M., Saez Jimenez, S., Sanchez Calderon, P., Sanchez Mendez, L., Sanchez Parra, S., Santolaya, C., Senan Sanz, M. R., Seoane Blanco, A., Serralvo, E., Sierra, N., Simon Valero, C., Sorribes Lopez, J., Teixido Fontanillas, M., Terns Riera, M., Tobajas, G., Torres, C., Torres Marques, J., Ubeda Pastor, M., Wirdby, A., Linden, J., Henriksson, K., Elmersson, M., Egilsson, A., Borjesson, U., Svard, G., Liu, B., Lindh, A., Olsson, L. -B., Gustavsson, M. (Lars) Andersson L. (Lisbeth) Andersson L., Benson, L., Bothin, C., Hajimirsadeghi, A., Kadir, K., Ericsson, M., Ohlsson, A., Lindvall, H., Svensson, P., Thorne, K., Handel, H., Platonov, P., Eriksson, B., Timberg, I., Romberg, K., Crisby, M., Karlsson, J. -E., Jensen, S. A., Andersson, A., Malmqvist, L., Martinsson, B., Bernsten, F., Engdahl, J., Thulin, J., Hot-Bjelac, A., Stalby, P., Aaroe, H., Ahbeck, E., Ahlmark, H., Al-Khalili, F., Bonkowski, G., Dzeletovic, S., Ekstrand, A. -B., Eriksson, G. -B., Floren, K., Grassjo, C., Hahn, S., Jaensson, P., Jansson, B., Jansson, J. -H., Kangert, R. -M., Koch, A., Kusiak, D., Lettenstrom, A., Lindberg, A., Lindholm, C. -J., Mannermyr, A., Mansson, K., Millborg, M., Nilsson, C., Ohlin, A. -M., Olofsson, A., Osberg, A., Pedersen, A., Risbecker, K., Rosenberg, K., Samuelsson, J., Shayesteh, M., Skoglund, K., Stjernberg, M., Thorsen, C., Beer, J. H., Debrunner, J., Amstutz, D., Bruegger, J., Elise, G., Grau, A., Guinand, A., Henriette, I., Saga, E., Winnik, S., Rudyk, I., Tseluyko, V., Karpenko, O., Zhurba, S., Kraiz, I., Kupnovytska, I., Serediuk, N., Mostovoy, Y., Ushakov, O., Koval, O., Kovalskyi, I., Svyshchenko, Y., Sychov, O., Stanislavchuk, M., Kraydashenko, O., Yagensky, A., Tykhonova, S., Fushtey, I., Belegai, R., Berko, G., Burdeuna, L., Chabanna, O., Daniuk, I., Ivanov, A., Kamenska, E., Kaplan, P., Khyzhnyak, O., Kizim, S., Matova, O., Medentseva, O., Mochonyi, V., Mospan, M., Nemtsova, V., Ovdiienko, T., Palamarchuk, O., Pavelko, M., Petrovskyy, R., Plevak, D., Proshak, O., Pyvovar, S., Rasputina, L., Romanenko, O., Romanova, O., Sapatyi, A., Shumakov, O., Stets, R., Todoriuk, L., Varenov, V., Chauhan, N., Goodwin, D., Saunders, P., Evans, R., Leese, J., Jhittay, P. S., Ross, A., Kainth, M. S., Pickavance, G., Mcdonnell, J., Williams, A., Gooding, T., Wagner, H., Suryani, S., Singal, A., Sircar, S., Bilas, R., Hutchinson, P., Wakeman, A., Stokes, M., Paul, N., Aziz, M., Ramesh, C., Wilson, P., Franklin, S., Fairhead, S., Thompson, J., St Joseph, V., Taylor, G., Tragen, D., Seamark, D., Paul, C., Richardson, M., Jefferies, A., Sharp, H., Jones, H., Giles, C., Page, M., Oginni, O., Aldegather, J., Wetherwell, S., Lumb, W., Evans, P., Scouller, F., Macey, N., Stipp, Y., West, R., Thurston, S., Wadeson, P., Matthews, J., Pandya, P., Gallagher, A., Railton, T., Sinha, B., Russell, D., Davies, J. A., Ainsworth, P., Jones, C. P., Weeks, P., Eden, J., Kernick, D., Murdoch, W., Lumley, L., Patel, R. P., Wong, S. W., Saigol, M., Ladha, K., Douglas, K., Cumberlidge, D. F., Bradshaw, C., Van Zon, G., Jones, K. P., Thomas, M. J., Watson, E., Sarai, B., Ahmad, N., Willcock, W., Cairns, J., Sathananthan, S., de Kare-Silver, N., Gilliland, A., Strieder, E., Howitt, A., Vishwanathan, B., Bird, N., Gray, D., Clark, M., Bisatt, J., Litchfield, J., Fisher, E., Fooks, T., Kelsall, A. R., Alborough, E., Wakeling, J., Parfitt, M., Milne, K., Rogers, S., Priyadharshan, R., Oliver, J. L., Davies, E., Abushal, S., Jacobs, M., Hutton, C., Walls, N. I., Thompson, R., Chigbo, C., Zaidi, S. M. A., Howard, M., Butter, K. C., Barrow, S., Little, H., Haq, I. U., Gibbons, L., Glencross, S., Mcleod, A. J., Poland, K., Mulholland, C., Warke, A., Conn, P., Burns, G., Smith, R. N., Lowe, S., Kamath, R., Dau, H. S., Webster, J., Hodgins, I., Vercoe, S., Roome, P. C., Pinnock, H., Patel, J. R. A., Ali, A., Hart, N., Davies, R., Stuart, E., Neden, C. A., Danielsen, M., Heath, R., Sharma, P., Galloway, S., Hawkins, C., Oliver, R., Aylward, M., Mannion, S., Braddick, M., Edwards, D., Rothwell, A. C., Sabir, A., Choudhary, F., Khalaque, S., Wilson, A., Peters, S., Coulson, W., Roberts, N., Heer, A., Coates, S., Ward, B., Jackson, D., Walton, S., Sterry, M., Wong, T., Boon, M., Bunney, R., Haria-Shah, R., Baron, R. T., Davies, S., Schatzberger, T., Hargreaves, N., Stephenson, T., Choi, H., Batson, R., Lucraft, L., Myhill, T., Estifano, S., Geatch, D., Wilkinson, J., Veale, R., Forshaw, K., Davies, T., Zaman, K., Vinson, P., Liley, C., Bandrapalli, M., Mcginty, P., Wastling, R., Mceleny, P., Beattie, A., Cooke, P., Wong, M., Gunasegaram, J., Pugsley, M., Ahmad, S., A'Court, C., Ayers, J., Bennett, J., Cartwright, S., Dobson, S., Dooldeniya, C., Flynn, A., Fox, R., Goram, J., Halpin, A., Hay, A., Jacobs, P., Jeffers, L., Lomax, L., Munro, I., Muvva, R., Powell, K., Randfield, S., Redpath, D., Reed, R., Rickenbach, M., Rogers, G., Saunders, P. B., Seamark, C., Shewring, J., Simmons, P., Simper, H., Stoddart, H., Sword, A., Thomas, N., Thomson, A., Blenkhorn, A., Singh, B., Van Gaal, W., Abhayaratna, W., Lehman, R., Roberts-Thomson, P., Kilian, J., Coulshed, D., Catanchin, A., Colquhoun, D., Kiat, H., Eccleston, D., French, J., Zimmett, L., Ayres, B., Phan, T., Blombery, P., Crimmins, D., O'Donnell, D., Choi, A., Astridge, P., Arstall, M., Jepson, N., Binnekamp, M., Lee, A., Rogers, J., Starmer, G., Carroll, P., Faunt, J., Aggarwala, A., Barry, L., Batta, C., Beveridge, R., Black, A., Bonner, M., Boys, J., Buckley, E., Campo, M., Carlton, L., Connelly, A., Conway, B., Cresp, D., Dimitri, H., Dixon, S., Dolman, M., Duroux, M., Eskandari, M., Eslick, R., Ferreira-Jardim, A., Fetahovic, T., Fitzpatrick, D., Geraghty, R., Gibbs, J., Grabek, T., H Modi, M., Hayes, K., Hegde, M. P., Hesketh, L., Hoffmann, B., Johnson, K., Juergens, C., Kassam, I., Lawlor, V., Lehman, M., Lehman, S., Leung, D., Mackay, S., Mackenzie, M., Mccarthy, C., Mcintosh, C., Mckeon, L., Morrison, H., Mussap, C., Myers, J. -D., Nagalingam, V., Oldfield, G., O'May, V., Palmer, J., Parsons, L., Patching, K., Patching, T., Paul, V., Plotz, M., Preston, S., Rashad, H., Ratcliffe, M., Raynes, S., Rose, J., Sanders, L., Seremetkoska, M., Setio, H., Shone, S., Shrestha, P., Singh, C., Singleton, C., Stoyanov, N., Sutcliffe, S., Swaraj, K., Tarrant, J., Thompson, S., Tsay, I. M., Vorster, M., Waldman, A., Wallis, L., Wilford, E., Wong, K., Luton, R., Pandey, A. S., Cheung, S., Beaudry, P., Ayala-Paredes, F., Berlingieri, J., Heath, J., Poirier, G., Du Preez, M., Nadeau, R., Dresser, G., Dhillon, R., Hruczkowski, T., Schweitzer, B., Coutu, B., Angaran, P., Macdonald, P., Vizel, S., Fikry, S., Parkash, R., Lavoie, A., Cha, J., Ramjattan, B., Bonet, J., Ahmad, K., Aro, L., Aves, T., Beaudry, K., Bergeron, C., Bigcanoe, J., Bignell, N., Breakwell, L., Burke, E., Carroll, L., Clarke, B., Cleveland, T., Daheb, S., Dehghani, P., Denis, I., Djaidani, Z., Dorian, P., Douglass, S., Dunnigan, J., Ewert, A., Farquhar, D., Fearon, A., Ferleyko, L., Fournier, D., Fox, B., Grenier, M. -C., Gulliver, W., Haveman, K., Hines, C., Hines, K., Jackson, A. M., Jean, C., Jethoo, G., Kahlon, R., Kelly, S., Kim, R., Korley, V., Kornder, J., Kwan, L., Largy, J., Lewis, C., Lewis, S., Mangat, I., Moor, R., Navratil, J., Neas, I., Otis, J., Otis, R., Pandey, M., Petrie, F., Pinter, A., Raines, M., Roberts, P., Robinson, M., Sas, G., Schulman, S., Snell, L., Spearson, S., Stevenson, J., Trahey, T., Wong, S., Wright, D., Abd El-Aziz, A., Abou Seif, S. K., El Din, M. G., El Etriby, S., Elbahry, A., El-Etreby, A., Elkhadem, M., Katta, A., Khairy, T., Mowafy, A., Nawar, M., Ohanissian, A., Reda, A., Reda, M., Salem, H., Sami, N., Samir, S., Setiha, M., Sobhy, M., Soliman, A., Taha, N., Tawfik, M., Zaatout, E., Kettles, D., Bayat, J., Siebert, H., Horak, A., Kelfkens, Y., Garda, R., Pillay, T., Guerra, M., van Zyl, L., Theron, H., Murray, A., Louw, R., Greyling, D., Mntla, P., Ueckermann, V., Loghdey, R., Ismail, S., Ahmed, F., Engelbrecht, J., Ramdass, A., Maharajh, S., Oosthuysen, W., Angel, G., Bester, C., Booysen, M., Boshoff, C., Cannon, C., Cassimjee, S., Chami, C., Conway, G., Davids, A., de Meyer, L., Du Plessis, G., Ellis, T., Henley, L., Karsten, M., Loyd, E., Marks, J., Mavhusa, L., Mostert, M., Page, A., Rikhotso, L., Salie, M., Sasto, J., Shaik, F., Skein, A., Smith, L., Tarr, G., Tau, T., van Zyl, F., Al Mahmeed, W., Yousef, G., Agrawal, A., Nathani, M., Ibrahim, M., Esheiba, E. M., Singh, R., Naguib, A., Abu-Mahfouz, M., Al Omairi, M., Al Naeemi, A., Maruthanayagam, R., Bazargani, N., Wassef, A., Gupta, R., Khan, M., Subbaraman, B., Abdul, A., Al Mulla, A., El Bardisy, S., Haridas, P., Jadhav, S., Magdaluyo, K., Makdad, M., Maqsood, I., Mohamed, R., Sharma, N., Sharma, R., Thanzeel, M., Canosa, R., Rama, P., Blumberg, E., Garcia, J., Mullen, P., Wilson, V., Quick, A., Ferrick, K., Kutayli, W. M., Cox, M., Franco, M., Falkowski, S., Mendelson, R., Williams, M., Miller, S., Beach, S., Alfieri, A., Gutowski, T., Haque, I., Reddy, R., Ahmed, W., Delafontaine, P., Diercks, D., Theodoro, D., Remmel, K., Alberts, M., Ison, R., Noveck, H., Duffy, P., Pitta, S., Nishijima, D., Treasure, C., Asafu-Adjaye, N., Ball, K., Bartlett, M., Bentley, M., Bowers, S., Brown, A., Browne, A., Cameron-Watts, J., Canova, M., Cassidy, D., Cervellione, K., Congal, S., Depauw, J., Dickerson, A., Eley, M., Evans, L., Felpel, S., Ferdinand, K., Fielder, D., Gentry, P., Haideri, A., Hakimi, F., Hartranft, E., Hawkins, B., Headlee, M., Henson, L., Herrick, C., Hicks, T., Jasinski, S., Jones, A., Jones, L., Jones, P., Karl, S., Keeling, M., Kerr, J., Knowles, P., Langdon, J., Lay, M., Lee, J. A., Lincoln, T., Malone, E., Merliss, A., Merritt, D., Minardo, J., Mooso, B., Orosco, C., Palumbo, V., Parker, M., Parrott, T., Paserchia, S., Pearl, G., Peterson, J., Pickelsimer, N., Purcell, T., Raynor, J., Raziano, S., Richard, C., Richardson, T., Robertson, C., Sage, A., Sanghera, T., Shaw, P., Shoemaker, J., Smith, K., Stephanie, B., Thatcher, A., Theobald, H., Thompson, N., Treasure, L., Tripti, T., Verdi, C., Worthy, V., UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Service de cardiologie
Subjects: Male, vitamin K antagonist, endocrine system, medicine.medical_specialty, Vitamin K, medicine.drug_class, Concordance, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Atrial Fibrillation, medicine, frequency in range, Humans, atrial fibrillation, international normalized ratio, time in therapeutic range, vitamin K antagonists, Hematology, 030212 general & internal medicine, International Normalized Ratio, Stroke, Aged, Fibrillation, Aged, 80 and over, business.industry, Anticoagulant, Warfarin, Atrial fibrillation, ta3121, Vitamin K antagonist, Middle Aged, medicine.disease, Decision Support Systems, Clinical, Confidence interval, Surgery, Cardiology, Female, medicine.symptom, business, Human, medicine.drug
Abstract: Vitamin K antagonist (VKA) therapy for stroke prevention in atrial fibrillation (AF) requires monitoring of the international normalized ratio (INR). We evaluated the agreement between two INR audit parameters, frequency in range (FIR) and proportion of time in the therapeutic range (TTR), using data from a global population of patients with newly diagnosed non-valvular AF, the Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF). Among 17168 patients with 1-year follow-up data available at the time of the analysis, 8445 received VKA therapy (±antiplatelet therapy) at enrolment, and of these patients, 5066 with ≥3 INR readings and for whom both FIR and TTR could be calculated were included in the analysis. In total, 70905 INRs were analysed. At the patient level, TTR showed higher values than FIR (mean, 56·0% vs 49·8%; median, 59·7% vs 50·0%). Although patient-level FIR and TTR values were highly correlated (Pearson correlation coefficient [95% confidence interval; CI], 0·860 [0·852–0·867]), estimates from individuals showed widespread disagreement and variability (Lin's concordance coefficient [95% CI], 0·829 [0·821–0·837]). The difference between FIR and TTR explained 17·4% of the total variability of measurements. These results suggest that FIR and TTR are not equivalent and cannot be used interchangeably.
Published: 2015

24. IL10 haplotypes are associated with diabetic nephropathy susceptibility in patients from western Mexico

Author: Edén Oceguera-Contreras, Ana Laura Pereira-Suárez, María Guadalupe Ramírez-Dueñas, Renato Parra-Michel, Luz E Chavarria-Buenrostro, Jorge F. Topete-Reyes, José Macías-Barragán, José Francisco Muñoz-Valle, Pedro Ernesto Sánchez-Hernández, Margarita Montoya-Buelna, Liliana B Hernandez-Carrillo, and Jorge Hernández-Bello
Subjects: 0301 basic medicine, Microbiology (medical), Male, medicine.medical_specialty, Clinical Biochemistry, Renal function, Gastroenterology, Polymorphism, Single Nucleotide, Nephropathy, Diabetic nephropathy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Genotype, medicine, Immunology and Allergy, Humans, Diabetic Nephropathies, Genetic Predisposition to Disease, Risk factor, Allele frequency, Aged, Aged, 80 and over, business.industry, Biochemistry (medical), Haplotype, Public Health, Environmental and Occupational Health, Hematology, Middle Aged, medicine.disease, Interleukin-10, Medical Laboratory Technology, 030104 developmental biology, Haplotypes, 030220 oncology & carcinogenesis, Case-Control Studies, Brief Reports, Female, business, Kidney disease
Abstract: INTRODUCTION: Diabetic Nephropathy (DN) is the main cause of chronic kidney disease (CKD) in diabetic patients. An IL‐10 imbalance could be related to renal hypertrophy and trigger to nephropathy. Three promoter polymorphisms (‐1082G>A, ‐819C>T, and ‐592C>A) at IL10 gene have been associated with changes in the IL‐10 expression and DN susceptibility. Therefore, the aim of this study was to analyze this association in Mexican patients with DN. METHODS: We conducted a case‐control study on 128 patients with DN and 150 control subjects (CS) from western Mexico. All patients were tested for IL10 polymorphisms by PCR‐RFLP. Allele frequencies, genotypes, and haplotypes were compared between groups. The significant haplotypes were correlated with patient clinical features. RESULTS: IL10 gene ATC haplotype (‐1082A/‐819T/‐592C) was found significantly more frequent in DN patients than in CS (P
Published: 2018

25. Adipose tissue and body composition in women six years after gestational diabetes: factors associated with development of type 2 diabetes

Author: Malin Lönn, Eva Jennische, Ulrika Andersson-Hall, Agneta Holmäng, Henrik Svensson, Staffan Edén, and Louise Wetterling
Subjects: 0301 basic medicine, Adult, Blood Glucose, medicine.medical_specialty, Histology, endocrine system diseases, type 2 diabetes mellitus, Adipose tissue, Adipokine, 030209 endocrinology & metabolism, adipocyte size, Type 2 diabetes, prediabetes, Weight Gain, Body Mass Index, 03 medical and health sciences, adipocyte fatty acid-binding protein, BMI, 0302 clinical medicine, Adipokines, Pregnancy, Internal medicine, Glucose Intolerance, medicine, Adipocytes, Humans, Prediabetes, body composition, business.industry, Type 2 Diabetes Mellitus, nutritional and metabolic diseases, Cell Biology, medicine.disease, gestational diabetes mellitus, adipose tissue, Gestational diabetes, Diabetes, Gestational, 030104 developmental biology, Endocrinology, Adipocyte fatty acid binding protein, Diabetes Mellitus, Type 2, Female, medicine.symptom, Insulin Resistance, business, Weight gain, Follow-Up Studies, Research Paper
Abstract: Factors differentiating women at highest risk of progression to type 2 diabetes mellitus (T2DM) after gestational diabetes mellitus (GDM) are incompletely known. Our aim was to characterize adipose tissue and body composition in relation to glucose metabolism in women with a history of GDM and to identify factors associated with development of T2DM. We examined glucose tolerance (OGTT), insulin sensitivity (HOMA-IR), body composition (anthropometry, air displacement plethysmography), and blood chemistry in 39 women 6 years after GDM. An adipose tissue biopsy was obtained to assess the size, number, and lipolytic activity of adipocytes, and adipokine release and density of immune cells and blood vessels in adipose tissue. Normal glucose tolerance (NGT) was identified in 31 women and impaired glucose metabolism (IGM) in 8. Women with IGM had higher BMI/fat mass, and related expected adipose tissue features, than women with NGT. Ethnicity was similar in the groups, but numerically there was a higher proportion of European women in the NGT group and a higher proportion of non-European women in the IGM group. BMI was the best discriminator of NGT versus IGM (multivariable logistic regression: OR = 1.34, P
Published: 2018

26. Identification and validation of single-sample breast cancer radiosensitivity gene expression predictors

Author: Irma Fredriksson, Johan Staaf, Jonas Bergh, Mårten Fernö, Per-Uno Malmström, Fredrik Wärnberg, Patrik Edén, Emma Niméus, and Martin Sjöström
Subjects: 0301 basic medicine, Oncology, medicine.medical_treatment, Estrogen receptor, Mastectomy, Segmental, Radiation Tolerance, 0302 clinical medicine, Breast cancer, Risk Factors, Surgical oncology, Local recurrence, Radioresistance, Middle Aged, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Combined Modality Therapy, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Receptors, Estrogen, 030220 oncology & carcinogenesis, Female, Adjuvant, Research Article, medicine.medical_specialty, Breast Neoplasms, lcsh:RC254-282, Radiosensitivity, 03 medical and health sciences, Internal medicine, medicine, Humans, Nanostring, Chemotherapy, Cancer och onkologi, Radiotherapy, business.industry, Gene Expression Profiling, medicine.disease, Radiation therapy, 030104 developmental biology, Ipsilateral breast tumor recurrence, nCounter, Cancer and Oncology, Radiotherapy, Adjuvant, Gene expression, Neoplasm Recurrence, Local, Transcriptome, business
Abstract: Background Adjuvant radiotherapy is the standard of care after breast-conserving surgery for primary breast cancer, despite a majority of patients being over- or under-treated. In contrast to adjuvant endocrine therapy and chemotherapy, no diagnostic tests are in clinical use that can stratify patients for adjuvant radiotherapy. This study presents the development and validation of a targeted gene expression assay to predict the risk of ipsilateral breast tumor recurrence and response to adjuvant radiotherapy after breast-conserving surgery in primary breast cancer. Methods Fresh-frozen primary tumors from 336 patients radically (clear margins) operated on with breast-conserving surgery with or without radiotherapy were collected. Patients were split into a discovery cohort (N = 172) and a validation cohort (N = 164). Genes predicting ipsilateral breast tumor recurrence in an Illumina HT12 v4 whole transcriptome analysis were combined with genes identified in the literature (248 genes in total) to develop a targeted radiosensitivity assay on the Nanostring nCounter platform. Single-sample predictors for ipsilateral breast tumor recurrence based on a k-top scoring pairs algorithm were trained, stratified for estrogen receptor (ER) status and radiotherapy. Two previously published profiles, the radiosensitivity signature of Speers et al., and the 10-gene signature of Eschrich et al., were also included in the targeted panel. Results Derived single-sample predictors were prognostic for ipsilateral breast tumor recurrence in radiotherapy-treated ER+ patients (AUC 0.67, p = 0.01), ER+ patients without radiotherapy (AUC = 0.89, p = 0.02), and radiotherapy-treated ER- patients (AUC = 0.78, p
Published: 2018

27. Temporal relationship of sleep apnea and acromegaly: a nationwide study

Author: Christina Dahlgren, Jeanette Wahlberg, Ann Sofie Nilsson, Britt Edén Engström, Maria Forsgren, Karl A. Franklin, Eva Marie Erfurth, Per Dahlqvist, Caroline Alkebro, Maria Warn, Oskar Ragnarsson, Charlotte Höybye, Pia Burman, Jenny Tiberg Persson, Anna Karin Åkerman, Konstantina Vouzouneraki, and Helena Wik
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Cross-sectional study, Endocrinology, Diabetes and Metabolism, Polysomnography, Prevalence, 030209 endocrinology & metabolism, Comorbidity, 030204 cardiovascular system & hematology, Endocrinology and Diabetes, Comorbidities, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Endocrinology, Sleep Apnea Syndromes, Diabetes mellitus, Acromegaly, medicine, Humans, Young adult, Aged, Aged, 80 and over, medicine.diagnostic_test, business.industry, Sleep apnea, Middle Aged, Risk factors, medicine.disease, respiratory tract diseases, Cross-Sectional Studies, Endokrinologi och diabetes, Female, Original Article, business
Abstract: PurposePatients with acromegaly have an increased risk of sleep apnea, but reported prevalence rates vary largely. Here we aimed to evaluate the sleep apnea prevalence in a large national cohort of patients with acromegaly, to examine possible risk factors, and to assess the proportion of patients diagnosed with sleep apnea prior to acromegaly diagnosis.MethodsCross-sectional multicenter study of 259 Swedish patients with acromegaly. At patients follow-up visits at the endocrine outpatient clinics of all seven university hospitals in Sweden, questionnaires were completed to assess previous sleep apnea diagnosis and treatment, cardiovascular diseases, smoking habits, anthropometric data, and S-IGF-1 levels. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale. Patients suspected to have undiagnosed sleep apnea were referred for sleep apnea investigations.ResultsOf the 259 participants, 75 (29%) were diagnosed with sleep apnea before the study start. In 43 (57%) of these patients, sleep apnea had been diagnosed before the diagnosis of acromegaly. After clinical assessment and sleep studies, sleep apnea was diagnosed in an additional 20 patients, yielding a total sleep apnea prevalence of 37%. Higher sleep apnea risk was associated with higher BMI, waist circumference, and index finger circumference. Sleep apnea was more frequent among patients with S-IGF-1 levels in the highest quartile.ConclusionSleep apnea is common among patients with acromegaly, and is often diagnosed prior to their acromegaly diagnosis. These results support early screening for sleep apnea in patients with acromegaly and awareness for acromegaly in patients with sleep apnea. Funding Agencies|Swedish Pituitary Registry; Department of Research and Development Vasternorrland County Council
Published: 2018

28. Morbihan Syndrome Successfully Treated with Omalizumab

Author: Carl Swartling, Pegah Kafi, and Inger Edén
Subjects: medicine.medical_specialty, Esthetics, Injections, Subcutaneous, Treatment outcome, MEDLINE, Omalizumab, Dermatology, Severity of Illness Index, Drug Administration Schedule, Text mining, Quality of life, Internal medicine, Severity of illness, lcsh:Dermatology, medicine, Edema, Humans, Dose-Response Relationship, Drug, business.industry, Syndrome, General Medicine, lcsh:RL1-803, Middle Aged, Treatment Outcome, Rosacea, Quality of Life, Female, business, medicine.drug
Published: 2019
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29. Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance

Author: Henrik Svensson, Staffan Edén, Agneta Holmäng, Birgitta Odén, Malin Lönn, Marja Bosaeus, Eva Jennische, Louise Wetterling, and Anders Odén
Subjects: Adult, Blood Glucose, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Subcutaneous Fat, Medicine (miscellaneous), Adipose tissue, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Fatty Acid-Binding Proteins, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Pregnancy, Internal medicine, Adipocytes, medicine, Body Fat Distribution, Humans, Insulin, Obesity, Nutrition and Dietetics, Adiponectin, business.industry, Organ Size, medicine.disease, Immunohistochemistry, Pregnancy Complications, Endocrinology, Adipose Tissue, Original Article, Female, Insulin Resistance, medicine.symptom, business, Body mass index, Weight gain
Abstract: Background/Objectives: Pregnancy is accompanied by fat gain and insulin resistance. Changes in adipose tissue morphology and function during pregnancy and factors contributing to gestational insulin resistance are incompletely known. We sought to characterize adipose tissue in trimesters 1 and 3 (T1/T3) in normal weight (NW) and obese pregnant women, and identify adipose tissue-related factors associated with gestational insulin resistance. Subjects/Methods: Twenty-two NW and 11 obese women were recruited early in pregnancy for the Pregnancy Obesity Nutrition and Child Health study. Examinations and sampling of blood and abdominal adipose tissue were performed longitudinally in T1/T3 to determine fat mass (air-displacement plethysmography); insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR); size, number and lipolytic activity of adipocytes; and adipokine release and density of immune cells and blood vessels in adipose tissue. Results: Fat mass and HOMA-IR increased similarly between T1 and T3 in the groups; all remained normoglycemic. Adipocyte size increased in NW women. Adipocyte number was not influenced, but proportions of small and large adipocytes changed oppositely in the groups. Lipolytic activity and circulating adipocyte fatty acid-binding protein increased in both groups. Adiponectin release was reduced in NW women. Fat mass and the proportion of very large adipocytes were most strongly associated with T3 HOMA-IR by multivariable linear regression (R2=0.751, P
Published: 2015
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30. Identification of Functional Prolactin (PRL) Receptor Gene Expression: PRL Inhibits Lipoprotein Lipase Activity in Human White Adipose Tissue

Author: Birgitta Odén, Louise Svensson, Staffan Edén, Birgitta Weijdegård, Håkan Billig, Barbro Edén, and Charlotte Ling
Subjects: Adult, endocrine system, medicine.medical_specialty, Adolescent, Receptors, Prolactin, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Gene Expression, Adipose tissue, White adipose tissue, Biology, Biochemistry, Endocrinology, Culture Techniques, Internal medicine, Lactation, Abdomen, medicine, Humans, Breast, RNA, Messenger, Enzyme Inhibitors, Receptor, Lipoprotein lipase, Prolactin receptor, Biochemistry (medical), Middle Aged, Prolactin, Lipoprotein Lipase, medicine.anatomical_structure, Adipose Tissue, Female, hormones, hormone substitutes, and hormone antagonists, Subcutaneous tissue
Abstract: During lactation serum levels of prolactin (PRL) are elevated, and the activity of lipoprotein lipase (LPL) is decreased in the adipose tissue and increased in the mammary gland. However, PRL has been suggested to affect the adipose tissue in an indirect fashion during lactation. In the present study, we demonstrated expression of four PRL receptor (PRLR) mRNA isoforms (L, I, S1(a), and S1(b)) in human sc abdominal adipose tissue and breast adipose tissue using RT-PCR/Southern blot analysis. In addition, L-PRLR [relative molecular mass (M(r)) 90,000] and I-PRLR (M(r) 50,000) protein expression was detected in human sc abdominal adipose tissue and breast adipose tissue using immunoblot analysis. Two additional protein bands with the molecular weight M(r) 40-35,000 were also detected. The direct effect of PRL on the regulation of LPL activity in human abdominal adipose tissue cultured in vitro was investigated. PRL (500 ng/ml) reduced the LPL activity in human adipose tissue to 31 +/- 7.7%, compared with control. GH (100 ng/ml) also reduced the LPL activity, to 45 +/- 8.6%, compared with control. In agreement with previous studies, cortisol increased the LPL activity and GH inhibited cortisol-induced LPL activity. Furthermore, we found that PRL also inhibited the cortisol-induced LPL activity. Taken together, these results demonstrate a direct effect of PRL, via functional PRLRs, in reducing the LPL activity in human adipose tissue, and these results suggest that LPL might also be regulated in this fashion during lactation.
Published: 2003
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31. GLP1 analogs as treatment of postprandial hypoglycemia following gastric bypass surgery: a potential new indication?

Author: Magnus Sundbom, Niclas Abrahamsson, Britt Edén Engström, and F. Anders Karlsson
Subjects: Adult, Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Gastric bypass, Treatment outcome, Gastric Bypass, Morbidly obese, medicine.disease_cause, Incretins, Endocrinology, Glucagon-Like Peptide 1, Diabetes mellitus, Internal medicine, medicine, Humans, Gastric bypass surgery, business.industry, General Medicine, Middle Aged, Postprandial Period, medicine.disease, Obesity, Hypoglycemia, Obesity, Morbid, Treatment Outcome, Postprandial, Diabetes Mellitus, Type 2, Female, business, Postprandial Hypoglycemia
Abstract: ObjectiveThe number of morbidly obese subjects submitted to bariatric surgery is rising worldwide. In a fraction of patients undergoing gastric bypass (GBP), episodes with late postprandial hypoglycemia (PPHG) develop 1–3 years after surgery. The pathogenesis of this phenomenon is not fully understood; meal-induced rapid and exaggerated increases of circulating incretins and insulin appear to be at least partially responsible. Current treatments include low-carbohydrate diets, inhibition of glucose intestinal uptake, reduction of insulin secretion with calcium channel blockers, somatostatin analogs, or diazoxide, a KATP channel opener. Even partial pancreatectomy has been advocated. In type 2 diabetes, GLP1 analogs have a well-documented effect of stabilizing glucose levels without causing hypoglycemia.DesignWe explored GLP1 analogs as open treatment in five consecutive GBP cases seeking medical attention because of late postprandial hypoglycemic symptoms.ResultsGlucose measured in connection with the episodes in four of the cases had been 2.7, 2.5, 1.8, and 1.6 mmol/l respectively. The patients consistently described that the analogs eliminated their symptoms, which relapsed in four of the five patients when treatment was reduced/discontinued. The drug effect was further documented in one case by repeated 24-h continuous glucose measurements.ConclusionThese open, uncontrolled observations suggest that GLP1 analogs might provide a new treatment option in patients with problems of late PPHG.
Published: 2013
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32. Psychosocial health and levels of employment in 851 hypopituitary Swedish patients on long-term GH therapy

Author: Margareta Bramnert, Thord Rosén, Bertil Ekman, Bengt-Åke Bengtsson, Charlotte Höybye, Helene Holmer, Britt Edén Engström, Marja Thorén, Johan Svensson, Marie Degerblad, Gudmundur Johannsson, Erik Hägg, Eva Marie Erfurth, and Lars Rylander
Subjects: Adult, Employment, Male, Pediatrics, medicine.medical_specialty, Alcohol Drinking, Hormone Replacement Therapy, Cross-sectional study, Endocrinology, Diabetes and Metabolism, Context (language use), Hypopituitarism, Growth hormone, Endocrinology, Adaptation, Psychological, medicine, Humans, Biological Psychiatry, Aged, Sweden, Endocrine and Autonomic Systems, business.industry, Smoking, Case-control study, Middle Aged, medicine.disease, Psychiatry and Mental health, Cross-Sectional Studies, Transgender hormone therapy, Case-Control Studies, Growth Hormone, Female, business, Psychosocial, Biomedical sciences
Abstract: The psychosocial health and working capacity in hypopituitary patients receiving long-term growth hormone (GH) therapy are unknown.Psychosocial health and levels of employment were compared between GH deficient (GHD) patients on long-term replacement and the general population.In a Swedish nationwide study, 851 GHD patients [101 childhood onset (CO) and 750 adult onset (AO)] and 2622 population controls answered a questionnaire regarding current living, employment and educational level, alcohol consumption and smoking habits. The median time on GH therapy for both men and women with CO GHD was 9 years and for AO GHD 6 years, respectively.As compared to the controls, the GHD patients were less often working full time, more often on sick leave/disability pension, and to a larger extent alcohol abstainers and never smokers (all; P0.05). Predominantly CO GHD women and men, but to some extent also AO GHD women and men, lived less frequently with a partner and more often with their parents. Particularly AO GHD craniopharyngioma women used more antidepressants, while AO GHD men with a craniopharyngioma used more analgesics.A working capacity to the level of the general population was not achieved among hypopituitary patients, although receiving long-term GH therapy. Patients were less likely to use alcohol and tobacco. The CO GHD population lived a less independent life.
Published: 2013
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33. Deaths Among Adult Patients With Hypopituitarism: Hypocortisolism During Acute Stress, and De Novo Malignant Brain Tumors Contribute to an Increased Mortality

Author: Eva Marie Erfurth, Anders F Mattsson, Per Dahlqvist, Pia Burman, F A Karlsson, Katarina Berinder, Bertil Ekman, Britt Edén Engström, Helene Holmer, Charlotte Höybye, Jeanette Wahlberg, Jonas Svensson, and Gudmundur Johannsson
Subjects: Adult, Male, medicine.medical_specialty, Hydrocortisone, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Autopsy, Context (language use), Hypopituitarism, Astrocytoma, Endocrinology and Diabetes, Biochemistry, Young Adult, Endocrinology, Cause of Death, Internal medicine, Humans, Medicine, Age of Onset, Aged, Cause of death, Adult patients, Brain Neoplasms, business.industry, Biochemistry (medical), Glioma, Middle Aged, medicine.disease, Radiation therapy, Standardized mortality ratio, Addison's disease, Acute Disease, Female, business, Stress, Psychological
Abstract: Context:Patients with hypopituitarism have an increased standardized mortality rate. The basis for this has not been fully clarified.Objective:To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up.Design and Methods:All-cause and cause-specific mortality in 1286 Swedish patients with hypopituitarism prospectively monitored in KIMS (Pfizer International Metabolic Database) 1995-2009 were compared to general population data in the Swedish National Cause of Death Registry. In addition, events reported in KIMS, medical records, and postmortem reports were reviewed.Main Outcome Measures:Standardized mortality ratios (SMR) were calculated, with stratification for gender, attained age, and calendar year during follow-up.Results:An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence interval: 1.18-1.70). Infections, brain cancer, and sudden death were associated with significantly increased SMRs (6.32, 9.40, and 4.10, respectively). Fifteen patients, all ACTH-deficient, died from infections. Eight of these patients were considered to be in a state of adrenal crisis in connection with death (medical reports and post-mortem examinations). Another 8 patients died from de novo malignant brain tumors, 6 of which had had a benign pituitary lesion at baseline. Six of these 8 subjects had received prior radiation therapy.Conclusion:Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease.
Published: 2013
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34. Gastric Bypass Surgery Elevates NT-ProBNP Levels

Author: Britt Edén Engström, F. Anders Karlsson, Niclas Abrahamsson, and Magnus Sundbom
Subjects: Adult, Blood Glucose, Male, medicine.medical_specialty, Gastroplasty, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Gastric Bypass, medicine.disease_cause, Body Mass Index, Predictive Value of Tests, Risk Factors, Weight loss, Internal medicine, Natriuretic Peptide, Brain, Weight Loss, medicine, Natriuretic peptide, Homeostasis, Humans, Insulin, Postoperative Period, Prospective Studies, cardiovascular diseases, Prospective cohort study, Heart Failure, Sweden, Nutrition and Dietetics, Gastric bypass surgery, business.industry, Fasting, Brain natriuretic peptide, medicine.disease, Obesity, Peptide Fragments, Obesity, Morbid, Treatment Outcome, cardiovascular system, Cardiology, Female, Surgery, medicine.symptom, business, human activities, Body mass index, hormones, hormone substitutes, and hormone antagonists, Obesity paradox, Follow-Up Studies, circulatory and respiratory physiology
Abstract: Brain natriuretic peptide (BNP) is produced in the heart in response to stretching of the myocardium. BNP levels are negatively correlated to obesity, and in obese subjects, a reduced BNP responsiveness has been described. Diet-induced weight loss has been found to lower or to have no effect on BNP levels, whereas gastric banding and gastric bypass have reported divergent results. We studied obese patients undergoing gastric bypass (GBP) surgery during follow-up of 1 year.Twenty patients, 18 women, mean 41 (SD 9.5) years old, with a mean preoperative BMI of 44.6 (SD 5.5) kg/m(2) were examined. N-terminal pro-brain natriuretic peptide (NT-ProBNP), glucose and insulin were measured preoperatively, at day 6 and months 1, 6 and 12. In 14 of the patients, samples were also taken at days 1, 2 and 4.The NT-ProBNP levels showed a marked increase during the postoperative week (from 54 pg/mL preop to 359 pg/mL on day 2 and fell to 155 on day 6). At 1 year, NT-ProBNP was 122 pg/mL (125 % increase, p = 0.01). Glucose, insulin and HOMA indices decreased shortly after surgery without correlation to NT-ProBNP change. Mean BMI was reduced from 44.6 to 30.5 kg/m(2) at 1 year and was not related to NT-ProBNP change.The data indicate that GBP surgery rapidly alters the tone of BNP release, by a mechanism not related to weight loss or to changes in glucometabolic parameters. The GBP-induced conversion of obese subjects, from low to high NT-ProBNP responders, is likely to influence the evaluation of cardiac function in GBP operated individuals.
Published: 2013
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35. Asymptomatic Cerebrospinal Fluid HIV-1 Viral Blips and Viral Escape During Antiretroviral Therapy: A Longitudinal Study

Author: Staffan Nilsson, Arvid Edén, Dietmar Fuchs, Magnus Gisslén, Lars Hagberg, Henrik Zetterberg, and Bo Svennerholm
Subjects: 0301 basic medicine, Adult, Male, Adolescent, Human immunodeficiency virus (HIV), HIV Infections, Biology, medicine.disease_cause, Asymptomatic, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, Cerebrospinal fluid, Interquartile range, medicine, Immunology and Allergy, Humans, 030212 general & internal medicine, Longitudinal Studies, Aged, Cerebrospinal Fluid, Retrospective Studies, Aged, 80 and over, Neopterin, RNA, Middle Aged, Viral Load, Virology, Antiretroviral therapy, 030104 developmental biology, Infectious Diseases, chemistry, Anti-Retroviral Agents, HIV-1, RNA, Viral, Female, medicine.symptom, Viral load
Abstract: We examined longitudinal cerebrospinal fluid (CSF) samples (median, 5 samples/patients; interquartile range [IQR], 3-8 samples/patient) in 75 neurologically asymptomatic human immunodeficiency virus (HIV)-infected patients receiving antiretroviral therapy. Twenty-seven patients (36%) had ≥1 CSF HIV RNA load of >20 copies/mL (23% had ≥1 load of >50 copies/mL), with a median HIV RNA load of 50 copies/mL (IQR, 32-77 copies/mL). In plasma, 42 subjects (52%) and 22 subjects (29%) had an HIV RNA load of >20 and >50 copies/mL, respectively. Two subjects had an increasing virus load in consecutive CSF samples, representing possible CSF escape. Of 418 samples, 9% had a CSF HIV RNA load of >20 copies/mL (5% had a load of >50 copies/mL) and 19% had a plasma HIV RNA load of >20 copies/mL (8% had a load of >50 copies/mL). A CSF-associated virus load of >20 copies/mL was associated with higher CSF level of neopterin. In conclusion, CSF escape was rare, and increased CSF HIV RNA loads usually represented CSF virus load blips.
Published: 2016

36. Increased Intrathecal Immune Activation in Virally Suppressed HIV-1 Infected Patients with Neurocognitive Impairment

Author: Arvid Edén, Thomas D Marcotte, Robert K Heaton, Staffan Nilsson, Henrik Zetterberg, Dietmar Fuchs, Donald Franklin, Richard W Price, Igor Grant, Scott L Letendre, Magnus Gisslén, and Koelsch, Kersten Kurt
Subjects: Central Nervous System, RNA viruses, Male, AIDS Dementia Complex, Physiology, lcsh:Medicine, Social Sciences, Neurodegenerative, Pathology and Laboratory Medicine, Nervous System, Biochemistry, Immunodeficiency Viruses, Neurofilament Proteins, Medicine and Health Sciences, 2.1 Biological and endogenous factors, Psychology, Public and Occupational Health, Longitudinal Studies, Aetiology, lcsh:Science, Cerebrospinal Fluid, Pediatric, Cognitive Neurology, Middle Aged, Vaccination and Immunization, Body Fluids, Infectious Diseases, Mental Health, Neurology, Anti-Retroviral Agents, Medical Microbiology, Viral Pathogens, Viruses, HIV/AIDS, Female, Anatomy, Pathogens, Research Article, Adult, General Science & Technology, Cognitive Neuroscience, Immunology, Antiretroviral Therapy, Microbiology, Immune Suppression, Neopterin, Immune Activation, Signs and Symptoms, Antiviral Therapy, Clinical Research, Diagnostic Medicine, Neuropsychology, Retroviruses, Acquired Cognitive Impairment, Humans, Microbial Pathogens, Neuropsychological Testing, lcsh:R, Lentivirus, Neurosciences, Organisms, Immunity, Biology and Life Sciences, HIV, Brain Disorders, HIV-1, Cognitive Science, lcsh:Q, Preventive Medicine, Biomarkers, Neuroscience
Abstract: OBJECTIVE:Although milder forms of HIV-associated neurocognitive disorder (HAND) remain prevalent, a correlation to neuronal injury has not been established in patients on antiretroviral therapy (ART). We examined the relationship between mild HAND and CSF neurofilament light protein (NFL), a biomarker of neuronal injury; and CSF neopterin, a biomarker of CNS immunoactivation, in virally suppressed patients on antiretroviral therapy (ART). DESIGN AND METHODS:We selected 99 subjects on suppressive ART followed longitudinally from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Based on standardized comprehensive neurocognitive performance (NP) testing, subjects were classified as neurocognitively normal (NCN; n = 29) or impaired (NCI; n = 70). The NCI group included subjects with asymptomatic (ANI; n = 37) or mild (MND; n = 33) HAND. CSF biomarkers were analyzed on two occasions. RESULTS:Geometric mean CSF neopterin was 25% higher in the NCI group (p = 0.04) and NFL and neopterin were significantly correlated within the NCI group (r = 0.30; p
Published: 2016
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37. Gene expression profiling indicates that immunohistochemical expression of CD40 is a marker of an inflammatory reaction in the tumor stroma of diffuse large B-cell lymphoma

Author: Johan Linderoth, Eva Cavallin-Ståhl, Patrik Edén, Karin Rydström, Mats Ehinger, Mats Jerkeman, and Patrick Joost
Subjects: CD4-Positive T-Lymphocytes, Male, Cancer Research, Pathology, medicine.medical_specialty, CD8-Positive T-Lymphocytes, Biology, Receptors, Urokinase Plasminogen Activator, Proinflammatory cytokine, Cohort Studies, Stroma, Biglycan, Biomarkers, Tumor, medicine, Humans, CD40 Antigens, Inflammation, Gene Expression Profiling, Macrophages, Proteolytic enzymes, Hematology, Integrin alphaV, Middle Aged, Prognosis, medicine.disease, Immunohistochemistry, Survival Analysis, Lymphoma, Gene expression profiling, Oncology, Cancer research, Female, Lymphoma, Large B-Cell, Diffuse, Diffuse large B-cell lymphoma
Abstract: Immunohistochemical expression of CD40 is seen in 60-70% of diffuse large B-cell lymphoma (DLBCL) and is associated with a superior prognosis. By using gene expression profiling we aimed to further explore the underlying mechanisms for this effect. Ninety-eight immunohistochemically defined CD40 positive or negative DLBCL tumors, 63 and 35 respectively, were examined using spotted 55K oligonucleotide arrays. CD40 expressing tumors were characterized by up-regulated expression of genes encoding proteins involved in cell-matrix interactions: collagens, integrin αV, proteoglycans and proteolytic enzymes, and antigen presentation. Immunohistochemistry confirmed that CD40 positive tumors co-express the proinflammatory proteoglycan biglycan (p = 0.005), which in turn correlates with the amount of infiltrating macrophages and CD4 and CD8 positive T-cells. We postulate that immunohistochemical expression of CD40 mainly reflects the inflammatory status in tumors. A high intratumoral inflammatory reaction may correlate with an increased autologous tumor response, and thereby a better prognosis.
Published: 2012
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38. Epidemiology and Long-term Survival in Acromegaly: A Study of 166 Cases Diagnosed between 1955 and 1984

Author: Björn Sjögren, Bengt-Åke Bengtsson, Staffan Edén, Ingrid Ernest, and Anders Odén
Subjects: Adult, Male, medicine.medical_specialty, Pediatrics, Population, Disease, Sex Factors, Acromegaly, Epidemiology, Long term survival, Internal Medicine, medicine, Humans, Endocrine system, education, Sweden, education.field_of_study, business.industry, Incidence (epidemiology), Age Factors, Middle Aged, Prognosis, medicine.disease, Surgery, Referral centre, Female, business, Follow-Up Studies
Abstract: In 1985, a follow-up investigation was performed of all patients with acromegaly (n = 166, 89 women and 77 men) seen over a 30-year period (1955-1984) at our Endocrine Unit, referral centre for the western region of Sweden (population 1.5 million). At the end of 1984, the prevalence of the disease was 6.9 per 10(5) inhabitants, the average incidence per year was 3.3 per million people. Mean age at diagnosis was 46.3 years and at death (n = 62) 64.1 years. About one-third of the patients (50/153), in whom it had been possible to estimate the total duration of the disease, had survived for more than 25 years. Mortality was, however, increased compared to the normal population. The observed number of deaths from vascular and malignant disorders was 32 and 15, respectively, compared to the expected numbers 9.0 (p less than 0.001) and 5.6 (p less than 0.01).
Published: 2009
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39. Hemoperfusion with Amberlite Resin in the Treatment of Self-Poisoning

Author: Elisabeth Edén, Andrew Heath, Dag Selander, Eric Mårtensson, Ingemar Wickström, Jarl Ahlmén, and Krister Delin
Subjects: Adult, Male, Time Factors, Metabolic Clearance Rate, Digitoxin, medicine.drug_class, medicine.medical_treatment, Tricyclic antidepressant, Mushroom Poisoning, Antidepressive Agents, Tricyclic, Internal Medicine, Humans, Medicine, Amitriptyline, Chloral Hydrate, Mushroom poisoning, Coma, business.industry, Middle Aged, Hemoperfusion, medicine.disease, Resins, Synthetic, Anesthesia, Female, Nortriptyline, Hemodialysis, medicine.symptom, business, medicine.drug
Abstract: Ten patients with various intoxications were treated with resin hemoperfusion. Three of four patients with grade IV coma due to tricyclic antidepressant (TCA) poisoning could be extubated during or on termination of hemoperfusion. Clearance values of 135--185 and 190--200 ml/min were obtained for amitriptyline and nortriptyline, respectively. One patient with severe chloral hydrate poisoning could be extubated after less than one hour's hemoperfusion. A clearance of 140 ml/min was obtained in a uremic patient with AV block II due to digitoxin intoxication. Four patients with mushroom poisoning were treated with combined hemoperfusion-hemodialysis. A transient fall in platelet count was seen in all patients. Resin hemoperfusion is of definite value in selected, severe cases of self-poisoning with psychotropic drugs such as TCA and possibly in cases of mushroom poisoning where the prognosis with hemodialysis and supportive therapy is doubtful.
Published: 2009
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40. Aniridia among children and teenagers in Sweden and Norway

Author: Caroline Beijar, Kristina Tornqvist, Ruth Riise, and Ulla Edén
Subjects: Male, Pediatrics, medicine.medical_specialty, Visual acuity, Adolescent, Cerebellar Ataxia, Visual Acuity, WAGR syndrome, Gillespie syndrome, Cataract, Young Adult, Age Distribution, Corneal Opacity, WAGR Syndrome, Intellectual Disability, Epidemiology, Prevalence, Humans, Medicine, Medical history, Sex Distribution, Young adult, Child, Aniridia, Sweden, Norway, business.industry, Infant, Glaucoma, Syndrome, General Medicine, Lens Subluxation, medicine.disease, eye diseases, Surgery, Ophthalmology, Child, Preschool, Population study, Female, sense organs, medicine.symptom, business
Abstract: Purpose: To investigate patients under the age of 20 with aniridia in Sweden and Norway in order to estimate the prevalence of aniridia, to describe clinical signs and identify complications in the young, which will help improve diagnostic tools and treatment. Methods: A thorough search for patients with aniridia (of all ages) was performed. Sixty-two of the 181 patients were under the age of 20. Fifty-two of them were examined and they constituted the study population. Patient history was obtained and all participants underwent clinical ophthalmologic examination, including photography. Blood samples were taken for mutation analysis. Results: Epidemiological data are only based on the results in Sweden. The age-specific prevalence in Sweden was 1:47 000, male/female ratio was 0.57, mean age 12 years and median age 14 years. The proportion of sporadic cases including WAGR (Wilms tumour, Aniridia, Genitourinary abnormalities, Mental Retardation) and Gillespie syndrome (aniridia, cerebellar ataxia and mental retardation) was 48%. In the entire study population (Sweden and Norway), the mean visual acuity (VA) was 0.2 (range 0.04-0.9). We found VA < 0.3 in 80% and
Published: 2008
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41. Lipid Mobilization Following Roux-en-Y Gastric Bypass Examined by Magnetic Resonance Imaging and Spectroscopy

Author: Jan Weis, Håkan Ahlström, M. Roos, B Edén Engström, Magnus Sundbom, Lars Johansson, Joel Kullberg, and F A Karlsson
Subjects: Adult, In vivo magnetic resonance spectroscopy, medicine.medical_specialty, Magnetic Resonance Spectroscopy, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Gastric Bypass, Adipose tissue, Young Adult, Insulin resistance, Internal medicine, medicine, Humans, Intramyocellular lipids, Muscle, Skeletal, Adiposity, Nutrition and Dietetics, Adiponectin, business.industry, Leptin, Insulin, Lipid Mobilization, Lipid metabolism, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Obesity, Morbid, Endocrinology, Liver, Female, Surgery, Insulin Resistance, business, Follow-Up Studies
Abstract: Recent developments of magnetic resonance imaging (MRI) and spectroscopy have made it possible to quantify lipid deposited in different tissues. To what extent an improvement of glucose tolerance shortly after Roux-en-Y gastric bypass surgery (RYGBP) is reflected in lipid levels in liver and skeletal muscle, markers of insulin resistance, has not been clarified. Whole-body MRI and MR spectroscopy (MRS) of liver and muscle and measurements of biochemical markers of glucose and lipid metabolism were performed at baseline and 1, 6, and 12 months following surgery in seven morbidly obese women. Volumes of adipose tissue depots and liver and muscle lipids were assessed from the MRI/MRS data. At 1 month postoperatively, body mass index and visceral and subcutaneous adipose tissues were reduced by 9%, 26%, and 10%, respectively, whereas no reductions in intrahepatocellular or skeletal intramyocellular lipid concentrations were found. Free fatty acid and beta-hydroxybutyrate levels were elevated two- and sixfold, respectively; glucose and insulin levels were lowered, indicating increased insulin sensitivity. Further weight loss up to 1 year was associated with reductions in all investigated lipid depots investigated, with the exception of the intramyocellular compartment. RYGBP causes rapid lipid mobilization from visceral and subcutaneous adipose depots and enhanced free fatty acid flux to the liver. An exceptional disconnection between liver fat and insulin sensitivity occurs in the early dynamic phase after surgery. However, in the late phase, the energy restriction imposed by the surgical procedure also reduces the liver lipids, but not the intramyocellular lipids.
Published: 2008
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42. Nonfatal Stroke, Cardiac Disease, and Diabetes Mellitus in Hypopituitary Patients on Hormone Replacement Including Growth Hormone

Author: Britt Edén Engström, Bertil Ekman, Johan Svensson, Eva Marie Erfurth, Marja Thorén, Charlotte Höybye, Marie Degerblad, Thord Rosén, Lars Rylander, Bo Norrving, Erik Hägg, Helene Holmer, Gudmundur Johannsson, Margareta Bramnert, Bengt-Åke Bengtsson, and Lars Hagmar
Subjects: Adult, Male, medicine.medical_specialty, Cardiotonic Agents, Heart Diseases, endocrine system diseases, Heart disease, Hormone Replacement Therapy, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Hypopituitarism, Disease, Biochemistry, Endocrinology, Internal medicine, Diabetes mellitus, Humans, Medicine, Hormone replacement therapy, Stroke, Aged, Human Growth Hormone, business.industry, Vascular disease, Biochemistry (medical), food and beverages, Middle Aged, medicine.disease, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Case-Control Studies, Female, Hormone therapy, business, Diabetic Angiopathies
Abstract: The impact of long-term GH replacement on cerebrovascular and cardiovascular diseases and diabetes mellitus in hypopituitary patients is unknown.The incidence of nonfatal stroke and cardiac events, and prevalence of type 2 diabetes mellitus (T2D) and cardioprotective medication were compared between cohorts of GH-deficient (GHD) patients and population controls.The incidence of nonfatal stroke and cardiac events was estimated retrospectively from questionnaires in 750 GHD patients and 2314 matched population controls. A prevalence of T2D and cardioprotective medication was recorded at the distribution of questionnaires. Time since first pituitary deficiency to start of GH therapy was 4 and 2 yr, and time on GH therapy was 6 yr for GHD women and men, respectively.Lifelong incidence of nonfatal stroke was tripled in GHD women and doubled in GHD men, but a decline was seen in both genders during periods after first pituitary hormone deficiency and GHD, during which most patients had GH therapy. The lifelong incidence of nonfatal cardiac events declined in GHD men during first pituitary hormone deficiency and GHD periods. GHD women had a higher prevalence of T2D and lipid-lowering medication, whereas GHD men had a higher prevalence of antihypertensive medication.The declined risks of nonfatal stroke in both genders and of nonfatal cardiac events in GHD men during periods on GH replacement may be caused by prescription of cardioprotective drugs and 6-yr GH replacement. GHD women had an increased prevalence of T2D, partly attributed to higher body mass index and lower physical activity.
Published: 2007
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43. Fracture Incidence in GH-Deficient Patients on Complete Hormone Replacement Including GH

Author: Marja Thorén, Thord Rosén, Marie Degerblad, Lars Hagmar, Bertil Ekman, Bengt-Åke Bengtsson, Helene Holmer, Britt Edén Engström, Gudmundur Johannsson, Johan Svensson, Lars Rylander, Eva Marie Erfurth, Margareta Bramnert, Charlotte Höybye, Karl-Göran Thorngren, and Erik Hägg
Subjects: Adult, Male, medicine.medical_specialty, Pediatrics, Adolescent, Hormone Replacement Therapy, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Population, Rate ratio, Hypopituitarism, Growth hormone deficiency, Fractures, Bone, Sex Factors, Risk Factors, Internal medicine, Humans, Medicine, Testosterone, Orthopedics and Sports Medicine, Child, education, Sweden, education.field_of_study, Human Growth Hormone, business.industry, Incidence, Incidence (epidemiology), Confounding, medicine.disease, Endocrinology, Estrogen, Population study, Female, business
Abstract: Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men. Introduction: The objective of this study was to evaluate fracture incidence in patients with confirmed growth hormone deficiency (GHD) on replacement therapy (including growth hormone [GH]) compared with population controls, while also taking potential Confounders and effect modifiers into account. Materials and Methods: Eight hundred thirty-two patients with GHD and 2581 matched population controls answered a questionnaire about fractures and other background information. Incidence rate ratio (IRR) and 95% CI for first fracture were estimated. The median time on GH therapy for childhood onset (CO) GHD men and women was 15 and 12 yr, respectively, and 6 and 5 yr for adult onset (AO) GHD men and women, respectively. Results: A more than doubled risk (IRR, 2.29; 95 % CI 1.23-4.28) for nonosteoporotic fractures was recorded in women with CO GHD, whereas no risk increase was observed among CO GHD men (IRR, 0.61) and AO GHD women (IRR, 1.08). A significantly decreased incidence of fractures (IRR, 0.54; 95% C1, 0.34-0.86) was recorded in AO GHD men. Conclusions: Increased fracture risk in CO GHD women can most likely be explained by interaction between oral estrogen and the GH-IGF-I axis. The adequate substitution rate of testosterone (90%) and GH (94%) may have resulted in significantly lower fracture risk in AO GHD men.
Published: 2007
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44. Estrogen Receptor β Expression Is Associated with Tamoxifen Response in ERα-Negative Breast Carcinoma

Author: Mårten Fernö, Cecilia Hegardt, Pär-Ola Bendahl, Lao H. Saal, Åke Borg, Jorma Isola, Mervi Laakso, Carsten Peterson, Per-Uno Malmström, Sofia K. Gruvberger-Saal, and Patrik Edén
Subjects: Selective Estrogen Receptor Modulators, Oncology, Cancer Research, medicine.medical_specialty, Gene Expression, Estrogen receptor, Breast Neoplasms, Kaplan-Meier Estimate, Breast cancer, Internal medicine, Biomarkers, Tumor, medicine, Estrogen Receptor beta, Humans, Estrogen receptor beta, Oligonucleotide Array Sequence Analysis, Randomized Controlled Trials as Topic, business.industry, Gene Expression Profiling, Estrogen Receptor alpha, Cancer, Prognosis, Antiestrogen, medicine.disease, Immunohistochemistry, Tamoxifen, Endocrinology, Chemotherapy, Adjuvant, Selective estrogen receptor modulator, Female, business, Estrogen receptor alpha, medicine.drug
Abstract: Purpose: Endocrine therapies, such as tamoxifen, are commonly given to most patients with estrogen receptor (ERα)–positive breast carcinoma but are not indicated for persons with ERα-negative cancer. The factors responsible for response to tamoxifen in 5% to 10% of patients with ERα-negative tumors are not clear. The aim of the present study was to elucidate the biology and prognostic role of the second ER, ERβ, in patients treated with adjuvant tamoxifen. Experimental Design: We investigated ERβ by immunohistochemistry in 353 stage II primary breast tumors from patients treated with 2 years adjuvant tamoxifen, and generated gene expression profiles for a representative subset of 88 tumors. Results: ERβ was associated with increased survival (distant disease-free survival, P = 0.01; overall survival, P = 0.22), and in particular within ERα-negative patients (P = 0.003; P = 0.04), but not in the ERα-positive subgroup (P = 0.49; P = 0.88). Lack of ERβ conferred early relapse (hazard ratio, 14; 95% confidence interval, 1.8-106; P = 0.01) within the ERα-negative subgroup even after adjustment for other markers. ERα was an independent marker only within the ERβ-negative tumors (hazard ratio, 0.44; 95% confidence interval, 0.21-0.89; P = 0.02). An ERβ gene expression profile was identified and was markedly different from the ERα signature. Conclusion: Expression of ERβ is an independent marker for favorable prognosis after adjuvant tamoxifen treatment in ERα-negative breast cancer patients and involves a gene expression program distinct from ERα. These results may be highly clinically significant, because in the United States alone, ∼10,000 women are diagnosed annually with ERα-negative/ERβ-positive breast carcinoma and may benefit from adjuvant tamoxifen.
Published: 2007
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45. Early Changes in Ghrelin following Roux-en-Y Gastric Bypass: Influence of Vagal Nerve Functionality?

Author: F. Anders Karlsson, Magnus Sundbom, Camilla Holdstock, and Britt Edén Engström
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Peptide Hormones, Endocrinology, Diabetes and Metabolism, Gastric Bypass, Radioimmunoassay, Pancreatic Polypeptide, Body Mass Index, Pepsin, Weight loss, Pepsinogen A, Internal medicine, Gastric Stump, Gastrins, Weight Loss, Gastric mucosa, medicine, Humans, Pancreatic polypeptide, Postoperative Period, Gastrin, Nutrition and Dietetics, biology, business.industry, Stomach, digestive, oral, and skin physiology, Vagus Nerve, Middle Aged, Ghrelin, medicine.anatomical_structure, Endocrinology, Gastric Mucosa, biology.protein, Female, Surgery, medicine.symptom, business, Ghrelin secretion
Abstract: Roux-en-Y gastric bypass (RYGBP) effectively produces massive weight reduction, improving health in morbidly obese patients. The mechanisms for the weight loss, and the fate of the excluded gastric mucosa, are not fully clarified. To what extent the appetite-stimulating gastric peptide ghrelin is affected remains controversial. Circulating concentrations of ghrelin, pancreatic polypeptide (PP), pepsinogen I (PGI) and gastrin were examined in 15 morbidly obese patients (median BMI 45 kg/m2) preoperatively, and on days 1, 2, 4, 6 and at months 1, 6 and 12 after RYGBP. Ghrelin levels fell on postoperative day 1 and increased after 1 month to preoperative levels, and rose further at 6 and 12 months. PP concentrations decreased on day 1 and subsequently returned to preoperative levels. PGI levels peaked transiently the first days after surgery and subsequently declined to lower than preoperative levels. Gastrin levels were gradually reduced postoperatively. Ghrelin and PP fall transiently after surgery, possibly due to vagal dysfunction, and ultimately, as weight loss ensues, ghrelin secretion increases to higher than preoperative levels. The RYBGP procedure affects the gastric mucosa, as reflected by a transient increase in circulating PGI, and subsequently, the mucosa in the excluded stomach is at rest, as shown by low levels of PGI and gastrin.
Published: 2007
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46. Gastric bypass alters the dynamics and metabolic effects of insulin and proinsulin secretion

Author: Johansson, H-E., Öhrvall, M., Haenni, A., Sundbom, M., Edén Engström, B., Karlsson, F. A., and Zethelius, B.
Subjects: Adult, Blood Glucose, Male, insulin, obesity, proinsulin, Gastric Bypass, Original Articles, Postprandial Period, Diabetes Mellitus, Type 2, gastric by-pass, Insulin Secretion, Humans, Female, Follow-Up Studies
Abstract: Aims Hyperproinsulinaemia is associated with obesity and is a risk factor for Type 2 diabetes. We explored the dynamics of proinsulin and insulin and postprandial effects on glucose and lipids in subjects who had undergone gastric bypass (GBP) surgery compared with morbidly obese (MO) subjects and normal weight control subjects (NW). Methods Subjects free from diabetes were recruited: 10 previously MO subjects [body mass index (BMI)±sd, 34.8±6.2kg/m2] who had undergone GBP surgery, 10 MO subjects (BMI 44±3.1kg/m2) and 12 NW control subjects (BMI 23.2±2.4kg/m2). After an overnight fast, a standard meal (2400 kJ) was ingested and glucose, proinsulin, insulin free fatty acids and triglycerides were determined up to 180 min. Results Fasting proinsulin was similar in the GBP group and NW control subjects, but threefold increased in MO subjects (P < 0.05). Postprandial AUC for glucose was similar in the three groups and AUC for proinsulin was high in MO, intermediate in the GBP group and lowest in NW control subjects (P for trend = 0.020). Postprandial proinsulin at 60 min was similar in the GBP group and MO subjects and twofold higher than in NW control subjects. Postprandial proinsulin at 180 min was normal in the GBP group, but fivefold increased in MO subjects (P = 0.008). Insulin increased rapidly at 30 min in the GBP group and was normal at 90 min, whereas insulin was still increased at 90–180 min in the MO subjects (P < 0.001). Conclusions MO subjects, free from diabetes, have elevated proinsulin concentrations in the fasting as well as the postprandial phase. After GBP surgery markedly lower fasting and postprandial proinsulin concentrations were observed, although BMI was higher compared with NW control subjects.
Published: 2007

47. Limited value of cabergoline in Cushing's disease: a prospective study of a 6-week treatment in 20 patients

Author: Bertil Ekman, F Anders Karlsson, Erik Schwarcz, Britt Edén-Engström, Jeanette Wahlberg, and Pia Burman
Subjects: Adult, Male, medicine.medical_specialty, Cabergoline, Hydrocortisone, Endocrinology, Diabetes and Metabolism, Context (language use), Disease, Adrenocorticotropic hormone, Endocrinology, Adrenocorticotropic Hormone, Internal medicine, medicine, Humans, Prospective Studies, Ergolines, Prospective cohort study, Pituitary ACTH Hypersecretion, Saliva, Aged, business.industry, Pituitary ACTH hypersecretion, General Medicine, Cushing's disease, Middle Aged, medicine.disease, Circadian Rhythm, Dopamine Agonists, Female, business, medicine.drug
Abstract: Context and objectiveThe role of cabergoline in Cushing's disease (CD) remains controversial. The experience is limited to case reports and few open studies that report the effects determined after ≥1 month of treatment. In prolactinomas and dopamine-responsive GH-secreting tumours, effects of cabergoline are seen within days or weeks. Here, we searched for short-term effects of cabergoline in CD.DesignTwenty patients (19 naïve and one recurrent) were included in a prospective study. Cabergoline was administered in increasing doses of 0.5–5 mg/week over 6 weeks.MethodsUrinary free cortisol (UFC) 24 h, morning cortisol and ACTH, and salivary cortisol at 0800, 1600 and 2300 h were determined once weekly throughout. Diurnal curves (six samples) of serum cortisol were measured at start and end.ResultsAt study end, the median cabergoline dose was 5 mg, range 2.5–5 mg/week. The prolactin levels, markers of compliance, were suppressed in all patients. During the treatment, hypercortisolism varied, gradual and dose-dependent reductions were not seen. Five patients had a >50% decrease of UFC, three had a >50% rise of UFC. Salivary cortisol at 2300 h showed a congruent >50% change with UFC in two of the five cases with decreased UFC, and in one of the three cases with increased UFC. One patient with decreases in both UFC and 2300 h salivary cortisol also had a reduction in diurnal serum cortisol during the course of the study.ConclusionsCabergoline seems to be of little value in the management of CD. Only one patient had a response-like pattern. Given the known variability of disease activity in CD, this might represent a chance finding.
Published: 2015

48. Landscape of familial isolated and young-onset pituitary adenomas: Prospective diagnosis in AIP mutation carriers

Author: Hernandez-Ramirez, L.C., Gabrovska, P., Denes, J., Stals, K., Trivellin, G., Tilley, D., Ferrau, F., Evanson, J., Ellard, S., Grossman, A.B., Roncaroli, F., Gadelha, M.R., Korbonits, M., Agha, A., Akker, S.A., Aflorei, E.D., Alföldi, S., Arlt, W., Atkinson, B., Aulinas-Masó, A., Aylwin, S.J., Backeljauw, P.F., Badiu, C., Baldeweg, S., Bano, G., Barkan, A., Barwell, J., Bernal-González, C., Besser, G., Bevan, J.S., Blair, J., Bouloux, P., Bradley, L., Buchfelder, M., Cakir, M., Canham N, ., Carroll, P., Chahal, H.S., Cheetham, T., Chentli, F., Clayton, R.N., Cohen, M., Cole, T., Courtney, H., Crowne, E., Cuthbertson, D., Dal J, ., Dalantaeva, N., Daousi, C., Darzy, K., Dattani, M., Davies, J.H., Davis, J., De Castro, M., De Marinis, L., Drake, W., Dutta, P., Dzeranova, L., Edén-Engström, B., Eeles, R., Elfving, M., Elston, M., Emmerson, L., Fersht, N., Fica, S., Fischli, S., Flanagan, D., Fleseriu, M., Freda, P.U., Friedman, T., Frohman, L.A., Gallego, P., Gevers, E., Gláz, E., Goldman, J.A., Goldstone, A.P., Goth, M., Greenhalgh, L., Grieve, J., Guitelman, M., Gürlek, A., Gurnell, M., Horvath, K., Howlett, T.A., Höybye, C., Hunter S, ., Iacovazzo D, ., Igaz, P., Inder, W.J., Iwata, T., Izatt, L., Jagadeesh, S., Kaltsas, G., Kaplan F, ., Karavitaki, N., Kastelan, D., Katz, M., Kearney, T., Khoo, B., Kiraly-Borri, C., Knispelis, R., Kovács, G.L., Kumar, A.V., Laws, E.R., Lechan, R.M., Levy, J., Lewandowski, K., Lo, J., Maartens, N., Matsuno, A., Mcgowan, B., Mcquaid, S.E., Medic-Stojanoska, M., Mercado-Atri, M., Mezősi, E., Miljic, D., Miller, K.K., Modenesi, S., Molitch, M.E., Monson, J., Morris, D.G., Morrison, P.J., Munir, A., Murray, R.D., Musat, M., Musolino, N., Nachtigall, L., Newell-Price, J., Ogilvie, A., Orme, S.M., Paşcanu, I., Patócs, A., Patterson, C., Pearce, S.H., Pecori Giraldi, F., Pfeifer, M., Popovic, V., Poplawski, N., Powell, M., Pullan, P., Quinton, R., Radian, S., Randeva, H., Ribeiro-Oliveira, A., Rodd, C., Ryan, F., Salvatori, R., Schöfl, C., Shears, D., Shotliff, K., Soares, B.S., Spada, A., Sperber, J., Spoudeas, H.A., Stewart, S., Storr, H., Strasburger, C., Street, M.E., Swords, F., Thakker, R.V., Tham, E., Thompson, C., Thorner, M.O., Tóth, M., Trainer, P.J., Tsagarakis, S., Tzanela, M., Vadász, J., Vaks, V., Verkauskiene, R., Wass, J.A., Webb, S.M., Weber, A., Yamada, S., Yarman, S., Yeoh, P., Yoshimoto, K., Zammitt, N.N., and İç hastalıkları
Subjects: Adenoma, Adult, Male, Adolescent, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Genetic Testing, Germ-Line Mutation, Growth Hormone-Secreting Pituitary Adenoma, Humans, Intracellular Signaling Peptides and Proteins, Longitudinal Studies, Middle Aged, Mutation, Pituitary Neoplasms, Prospective Studies, Young Adult, Endocrinology, Diabetes and Metabolism, Biochemistry, Endocrinology, Clinical Biochemistry, Biochemistry (medical), Observational Study, Settore MED/13 - Endocrinologia, Journal Article, 80 and over, Preschool, JCEM Online: Advances in Genetics, Research Support, Non-U.S. Gov't
Abstract: Context:Familial isolated pituitary adenoma (FIPA) due to aryl hydrocarbon receptor interacting protein (AIP) gene mutations is an autosomal dominant disease with incomplete penetrance. Clinical screening of apparently unaffected AIP mutation (AIPmut) carriers could identify previously unrecognized disease.Objective:To determine the AIP mutational status of FIPA and young pituitary adenoma patients, analyzing their clinical characteristics, and to perform clinical screening of apparently unaffected AIPmut carrier family members.Design:This was an observational, longitudinal study conducted over 7 years.Setting:International collaborative study conducted at referral centers for pituitary diseases.Participants:FIPA families (n = 216) and sporadic young-onset (≤30 y) pituitary adenoma patients (n = 404) participated in the study.Interventions:We performed genetic screening of patients for AIPmuts, clinical assessment of their family members, and genetic screening for somatic GNAS1 mutations and the germline FGFR4 p.G388R variant.Main Outcome Measure(s):We assessed clinical disease in mutation carriers, comparison of characteristics of AIPmut positive and negative patients, results of GNAS1, and FGFR4 analysis.Results:Thirty-seven FIPA families and 34 sporadic patients had AIPmuts. Patients with truncating AIPmuts had a younger age at disease onset and diagnosis, compared with patients with nontruncating AIPmuts. Somatic GNAS1 mutations were absent in tumors from AIPmut-positive patients, and the studied FGFR4 variant did not modify the disease behavior or penetrance in AIPmut-positive individuals. A total of 164 AIPmut-positive unaffected family members were identified; pituitary disease was detected in 18 of those who underwent clinical screening.Conclusions:A quarter of the AIPmut carriers screened were diagnosed with pituitary disease, justifying this screening and suggesting a variable clinical course for AIPmut-positive pituitary adenomas.
Published: 2015
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49. Gene expression profilers and conventional clinical markers to predict distant recurrences for premenopausal breast cancer patients after adjuvant chemotherapy

Author: Carsten Peterson, Carina Strand, Emma Niméus-Malmström, Cecilia Ritz, Mårten Fernö, Mattias Ohlsson, Anders Johnsson, Patrik Edén, and Görel Östberg
Subjects: Adult, Oncology, Cancer Research, medicine.medical_specialty, DNA, Complementary, Cyclophosphamide, medicine.medical_treatment, Breast Neoplasms, breast cancer, Breast cancer, Predictive Value of Tests, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Mastectomy, cDNA microarray, Chemotherapy, drug resistance, Receiver operating characteristic, business.industry, Gene Expression Profiling, Odds ratio, Middle Aged, medicine.disease, Confidence interval, Surgery, Methotrexate, Premenopause, ROC Curve, Chemotherapy, Adjuvant, Cancer and Oncology, RNA, Nottingham Prognostic Index, Female, Fluorouracil, Neoplasm Recurrence, Local, business, prognostic markers, medicine.drug
Abstract: A large proportion of breast cancer patients are treated with adjuvant chemotherapy after the primary operation, but some will recur in spite of this treatment. In order to achieve an improved and more individualised therapy, our knowledge in mechanisms for drug resistance needs to be increased. We have investigated to what extent cDNA microarray measurements could distinguish the likelihood of recurrences after adjuvant CMF (cyclophosphamide, methotrexate and 5-fluorouracil) treatment of premenopausal, lymph node positive breast cancer patients, and have also compared this with the corresponding performance when using conventional clinical variables. We tried several gene selection strategies, and built classifiers using the resulting gene lists. The best performing classifier with odds ratio (OR) = 6.5 (95% confidence interval (CI) = 1.4-62) did not outperform corresponding classifiers based on clinical variables. For the clinical variables, calibrated on the samples, either using all the clinical parameters or the Nottingham Prognostic Index (NPI) parameters, the areas under the receiver operating characteristics (ROC) curve were 0.78 and 0.79, respectively. The ORs at 90% sensitivity were 15 (95% CI = 3.1-140) and 10 (95% CI = 2.1-97), respectively. Our data have provided evidence for a comparable prediction of clinical outcome in CMF-treated breast cancer patients using conventional clinical variables and gene expression based markers. (c) 2006 Elsevier Ltd. All rights reserved.
Published: 2006
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50. Meal suppression of circulating ghrelin is normalized in obese individuals following gastric bypass surgery

Author: Magnus Sundbom, Britt Edén Engström, F A Karlsson, Margareta Öhrvall, and Lars Lind
Subjects: Adult, Blood Glucose, Male, medicine.medical_specialty, Peptide Hormones, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Gastric bypass, Gastric Bypass, Appetite, Appetite Stimulants, Medicine (miscellaneous), medicine.disease_cause, Eating, Surgical anastomosis, Internal medicine, medicine, Humans, Insulin, Obesity, Pancreatic hormone, Meal, Nutrition and Dietetics, Gastric bypass surgery, business.industry, digestive, oral, and skin physiology, Postprandial Period, medicine.disease, Ghrelin, digestive system diseases, Cross-Sectional Studies, Endocrinology, Female, business, hormones, hormone substitutes, and hormone antagonists
Abstract: It has been proposed that the success of maintained weight loss in morbidly obese subjects following Roux-en-Y gastric bypass (RYGBP) surgery depends on inappropriately low circulating concentrations of the appetite-stimulating peptide ghrelin, being unresponsive to food intake. In this study, this hypothesis was examined.Cross-sectional study with repeated blood samples in 40 subjects after 14 h of prolonged overnight fasting followed by a standardized mixed meal (770 kcal).Twenty men and 20 women were included: 10 middle-aged morbidly obese (body mass index (BMI) 43.9+/-3.3 kg/m(2)), 10 middle-aged subjects who had undergone RYGBP at the Uppsala University Hospital (BMI 34.7+/-5.8 kg/m(2)), 10 middle-aged non-obese (BMI 23.5+/-2.2 kg/m(2)) and 10 young non-obese (BMI 22.7+/-1.8 kg/m(2)).Ghrelin, glucose and insulin levels were analysed pre- and postprandially.In the morbidly obese, ghrelin concentrations were lower in the morning than in the RYGBP group and did not change following the meal. In the RYGBP group, fasting ghrelin levels fell after meal intake and showed similar suppression as both age-matched and young non-obese controls. The RYGBP surgery resulted in an increased meal-induced insulin secretion, which was related to the degree of postprandial ghrelin suppression.The present study demonstrates low circulating concentrations of ghrelin and blunted responses to fast and feeding in morbidly obese subjects. Marked weight reduction after RYGBP at our hospital is followed by a normalization of ghrelin secretion, illustrated by increased fasting levels compared to the preoperative obese state and regain of meal-induced ghrelin suppression.
Published: 2006
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