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10,796 results on '"Rasmussen AS"'

1. Multiple endocrine neoplasia type 1 (MEN-1) and neuroendocrine neoplasms (NENs)

Author

Maria Rossing, Ulrich Knigge, Åse Krogh Rasmussen, Ulla Feldt-Rasmussen, Grigoris Effraimidis, and Peter Oturai

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Genetic counseling, Multiple endocrine neoplasia, type 1 (MEN 1), 03 medical and health sciences, 0302 clinical medicine, Quality of life, Proto-Oncogene Proteins, Internal medicine, Biomarkers, Tumor, Multiple Endocrine Neoplasia Type 1, Humans, Medicine, Genetic Predisposition to Disease, MEN1, Tumour suppressor gene, Multiple endocrine neoplasia, Gastrointestinal Neoplasms, business.industry, Incidence (epidemiology), medicine.disease, Pancreatic Neoplasms, Neuroendocrine Tumors, 030104 developmental biology, medicine.anatomical_structure, Gastrinoma, 030220 oncology & carcinogenesis, business, Pancreas, Diagnostic Techniques, Radioisotope
Abstract

Neuroendocrine neoplasms (NENs) are relatively rare neoplasms with 6.4-times increasing age-adjusted annual incidence during the last four decades. NENs arise from neuroendocrine cells, which release hormones in response to neuronal stimuli and they are distributed into organs and tissues. The presentation and biological behaviour of the NENs are highly heterogeneous, depending on the organ. The increased incidence is mainly due to increased awareness and improved detection methods both in the majority of sporadic NENs (non-inherited), but also the inherited groups of neoplasms appearing in at least ten genetic syndromes. The most important one is multiple endocrine neoplasia type 1 (MEN-1), caused by mutations in the tumour suppressor gene MEN1. MEN-1 has been associated with different tumour manifestations of NENs e.g. pancreas, gastrointestinal tract, lungs, thymus and pituitary. Pancreatic NENs tend to be less aggressive when arising in the setting of MEN-1 compared to sporadic pancreatic NENs. There have been very important improvements over the past years in both genotyping, genetic counselling and family screening, introduction and validation of various relevant biomarkers, as well as newer imaging modalities. Alongside this development, both medical, surgical and radionuclide treatments have also advanced and improved morbidity, quality of life and mortality in many of these patients. Despite this progress, there is still space for improving insight into the genetic and epigenetic factors in relation to the biological mechanisms determining NENs as part of MEN-1. This review gives a comprehensive update of current evidence for co-occurrence, diagnosis and treatment of MEN-1 and neuroendocrine neoplasms and highlight the important progress now finding its way to international guidelines in order to improve the global management of these patients.

Published
2022

2. Australian and Danish nurses’ and midwives’ wellbeing during COVID-19: A comparison study

Author

Bodil Rasmussen, Damien Khaw, Melody Trueman, Cherene Ockerby, Ana Hutchinson, Shane Crowe, Julie Considine, Susan Sweeney, Suellen Bruce, Karen Wynter, Maryann Street, Alison M. Hutchinson, Mette Juel Rothmann, Mette Maria Skjoeth, and Sara Holton

Subjects
medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Denmark, Nurses, Article, Midwives, Danish, Pandemic, Medicine, General Nursing, Depression (differential diagnoses), Wellbeing, business.industry, Australia, COVID-19, Mental health, language.human_language, Distress, Scale (social sciences), Family medicine, language, Anxiety, medicine.symptom, business
Abstract

Background: Most investigations of nurses’ and midwives’ psychological wellbeing during the COVID-19 pandemic have been conducted in a single setting. Aim: To assess and compare the psychological wellbeing of nurses and midwives in Australia and Denmark during the COVID-19 pandemic. Methods: Nurses and midwives employed at four metropolitan health services in Australia and one in Denmark completed an anonymous online survey, which assessed depression, anxiety, and stress symptoms (The Depression, Anxiety and Stress Scale - 21 Items (DASS-21)), and sociodemographic and employment factors. Findings: Completed surveys were received from 3001 nurses and midwives (1611 Australian and 1390 Danish). Overall, approximately one in seven of the nurses and midwives surveyed reported moderate to extremely severe levels of depression (n = 399, 13.5%), anxiety (n = 381, 12.9%) and stress (n = 394, 13.4%). Australian nurses’ and midwives’ scores on all DASS-21 subscales were significantly higher (representing higher levels of depression, anxiety and stress) than the scores for the Danish nurses and midwives. Fewer years of clinical experience, living in Australia and being employed on a part-time basis were significantly associated with higher levels of psychological distress. Discussion: A considerable proportion of nurses and midwives experienced distress during the COVID-19 pandemic; however, the proportion and severity varied by country. Australian nurses and midwives experienced higher levels of distress than their Danish colleagues. Conclusion: Nurses and midwives working in countries with relatively low numbers of COVID-19 cases and deaths are also likely to experience psychological distress. Nurses and midwives would benefit from targeted country-specific support and wellbeing initiatives.

Published
2022

3. Effects of working memory load and CS-US intervals on delay eyeblink conditioning

Author

Leila Etemadi, Anders Rasmussen, Dan-Anders Jirenhed, and Neurosciences

Subjects
Linear mixed effect model, medicine.medical_specialty, genetic structures, Working memory, Interstimulus interval, Cerebellar function, Stimulus (physiology), Audiology, behavioral disciplines and activities, Education, Eyeblink conditioning, Developmental Neuroscience, medicine, Conditioning, Psychology, Motor learning, psychological phenomena and processes
Abstract

Background: Eyeblink conditioning is used in many different species to study motor learning and make inferences about cerebellar function. However, considerable discrepancies in performance between different species combined with evidence that awareness of stimulus contingencies affects performance indicates that eyeblink conditioning in part reflects activity in non-cerebellar regions. This questions whether eyeblink conditioning can be used as a pure measure of cerebellar function in humans. Methods: Here we explored two ways to reduce non-cerebellar influences on performance in eyeblink conditioning: (1) using a short interstimulus interval, and (2) having participants do working memory tasks during the conditioning. Data were analyzed, and the influence of the interstimulus interval and working memory tasks was assessed using a linear mixed effects model. Results: Our results show that subjects trained with a short interstimulus interval (150ms and 250ms) produce few conditioned responses after 100 trials. For subjects trained with a longer interstimulus interval (500ms), those who did working memory tasks produced fewer conditioned responses and had a more gradual learning curve, more akin to those reported in the animal literature. Conclusions: Our results suggest that having subjects perform working memory tasks during eyeblink conditioning can be a viable strategy to reduce non-cerebellar interference in the learning.

Published
2023

4. Effect on cardiac function among patients with type 2 diabetes following high-dose mineralocorticoid receptor antagonist using echocardiography; data from the MIRAD randomized clinical trial

Author

Morten Schou, Caroline Kistorp, Jens Faber, Thomas Kümler, Patrick Rossignol, Niels H Brandt-Jacobsen, Morten Dalsgaard, Jon J Rasmussen, and Marie Louise Johansen

Subjects
Global longitudinal strain, Cardiac function curve, medicine.medical_specialty, Mineralocorticoid receptor antagonist, business.industry, Systolic and diastolic function, Type 2 diabetes, medicine.disease, law.invention, Mineralocorticoid receptor, Text mining, Randomized controlled trial, law, Internal medicine, medicine, Cardiology, High-dose eplerenone, business, Cardiology and Cardiovascular Medicine
Abstract

Background Early heart failure prevention is central in patients with type 2 diabetes, and mineralocorticoid receptor antagonists (MRAs) have shown to improve prognosis. We investigated the effect of high-dose MRA, eplerenone, on cardiac function and structure in patients with type 2 diabetes and established or increased risk of cardiovascular disease but without heart failure. Methods In the current randomized, placebo-controlled clinical trial, 140 patients with high-risk type 2 diabetes were randomized to high-dose eplerenone (100–200 mg daily) or placebo as add-on to standard care for 26 weeks. Left ventricular systolic and diastolic function, indexed left ventricular mass (LVMi), and global longitudinal strain (GLS) were assessed using echocardiography at baseline and after 26 weeks of treatment. Results Of the included patients, 138 (99%) had an echocardiography performed at least once. Baseline early diastolic in-flow velocity (E-wave) indexed by mitral annulus velocity (e’) was mean (SD) 11.1 (0.5), with 31% of patients reaching above 12. No effect of treatment on diastolic function was observed measured by E/e’ (0.0, 95%CI [-1.2 to 1.2], P = 0.992) or E/A (-0.1, 95%CI [-0.2 to 0.0], P = 0.191). Mean left ventricular ejection fraction (LVEF) at baseline was 59.0% (8.0). No improvement in systolic function was observed when comparing groups after 26 weeks (LVEF: 0.9, 95%CI [-1.1 to 2.8], P = 0.382; GLS: -0.4%, 95%CI [-1.5 to 0.6], P = 0.422), nor in LVMi (-3.8 g/m2 95%CI [-10.2 to 2.7], P = 0.246). Conclusion In the present echo sub-study, no change in left ventricular function was observed following high-dose MRA therapy in patients with type 2 diabetes when evaluated by conventional echocardiography. Trial registration Date of registration 25/08/2015 (EudraCT number: 2015–002,519-14).

Published
2023

5. Hematoma and deep surgical site infection following primary breast augmentation: A retrospective review of 1128 patients

Author

Louise E. Rasmussen, Mathilde N. Hemmingsen, Mikkel Herly, Peter Andersen, Peter V Vester-Glowinski, Tim K. Weltz, Mathias Ørholt, Jens Jørgen Elberg, Faye Sarmady, and Andreas Larsen

Subjects
Hematoma, medicine.medical_specialty, Retrospective review, Multivariate analysis, business.industry, Breast Implants, Mammaplasty, Medical record, Postoperative hematoma, medicine.disease, Surgery, Postoperative Complications, Humans, Surgical Wound Infection, Medicine, Female, Implant, business, Breast Implantation, Breast augmentation, Surgical site infection, Retrospective Studies
Abstract

Summery Background Breast augmentation is one of the most frequently performed cosmetic surgeries worldwide. Some of the most severe short-term complications after breast augmentation are hematoma and deep surgical site infection. However, these complications are relatively rare; therefore, large patient populations are required to perform statistical analyses. In this study, we provide a detailed analysis of the complications after primary breast augmentation with an emphasis on deep surgical site infection and hematoma. Method We retrospectively reviewed the medical records of women who underwent primary breast augmentation performed without the use of pocket irrigation between 2012 and 2019 in a single private clinic. A cumulative hazard function and a multivariate analysis on the risk of hematoma were performed. Results We included 1128 patients in the study. Thirty patients (2.7%) developed postoperative hematoma after a median time of 14 hours (IQR 5 hours-9 days). Six patients (0.5%) contracted a deep surgical site infection after a median time of 14 days (range 4-41 days). Neither age, BMI, implant volume or implant placement were significantly associated with hematoma. Conclusion Our findings support that the risk of hematoma after primary breast augmentation is highest within the first 24 hours after the surgery. This time period should be considered when planning postoperative care for these patients. We did not find an increased rate of deep surgical site infection compared with studies of breast augmentations with pocket irrigation. Further studies and meta-analyses are needed to explore the effect of pocket irrigation and other risk factors.

Published
2022

6. Simultaneous pelvic exenteration and liver resection for primary rectal cancer with synchronous liver metastases: results from the PelvEx Collaborative

Author

Kelly, M. E., Aalbers, A. G. J., Abdul Aziz, N., Abecasis, N., Abraham‐Nordling, M., Akiyoshi, T., Alberda, W., Albert, M., Andric, M., Angenete, E., Antoniou, A., Auer, R., Austin, K. K., Aziz, O., Baker, R. P., Bali, M., Baseckas, G., Bebington, B., Bednarski, B. K., Beets, G. L., Berg, P. L., Beynon, J., Biondo, S., Boyle, K., Bordeianou, L., Bremers, A. B., Brunner, M., Buchwald, P., Bui, A., Burgess, A., Burger, J. W. A., Burling, D., Burns, E., Campain, N., Carvalhal, S., Castro, L., Caycedo‐Marulanda, A., Chan, K. K. L., Chang, G. J., Chew, M. H., Chong, P. C., Christensen, H. K., Clouston, H., Codd, M., Collins, D., Colquhoun, A. J., Corr, A., Coscia, M., Coyne, P. E., Creavin, B., Croner, R. S., Damjanovic, L., Daniels, I. R., Davies, M., Davies, R. J., Delaney, C. P., Denost, Q., Deutsch, C., Dietz, D., Domingo, S., Dozois, E. J., Duff, M., Eglinton, T., Enrique‐Navascues, J. M., Espin‐Basany, E., Evans, M. D., Fearnhead, N. S., Flatmark, K., Fleming, F., Frizelle, F. A., Gallego, M. A., Garcia‐Granero, E., Garcia‐Sabrido, J. L., Gentilini, L., George, M. L., Ghouti, L., Giner, F., Ginther, N., Glynn, R., Golda, T., Griffiths, B., Harris, D. A., Hagemans, J. A. W., Hanchanale, V., Harji, D. P., Helewa, R. M., Heriot, A. G., Hochman, D., Hohenberger, W., Holm, T., Hompes, R., Jenkins, J. T., Kaffenberger, S., Kandaswamy, G. V., Kapur, S., Kanemitsu, Y., Kelley, S. R., Keller, D. S., Khan, M. S., Kiran, R. P., Kim, H., Kim, H. J., Koh, C. E., Kok, N. F. M., Kokelaar, R., Kontovounisios, C., Kristensen, H. Ø., Kroon, H. M., Kusters, M., Lago, V., Larsen, S. G., Larson, D. W., Law, W. L., Laurberg, S., Lee, P. J., Limbert, M., Lydrup, M. L., Lyons, A., Lynch, A. C., Mantyh, C., Mathis, K. L., Margues, C. F. S., Martling, A., Meijerink, W. J. H. J., Merkel, S., Mehta, A. M., McArthur, D. R., McDermott, F. D., McGrath, J. S., Malde, S., Mirnezami, A., Monson, J. R. T., Morton, J. R., Mullaney, T. G., Negoi, I., Neto, J. W. M., Nguyen, B., Nielsen, M. B., Nieuwenhuijzen, G. A. P., Nilsson, P. J., O’Connell, P. R., O’Dwyer, S. T., Palmer, G., Pappou, E., Park, J., Patsouras, D., Pellino, G., Peterson, A. C., Poggioli, G., Proud, D., Quinn, M., Quyn, A., Radwan, R. W., van Ramshorst, G. H., Rasheed, S., Rasmussen, P. C., Regenbogen, S. E., Renehan, A., Rocha, R., Rochester, M., Rohila, J., Rothbarth, J., Rottoli, M., Roxburgh, C., Rutten, H. J. T., Ryan, É. J., Safar, B., Sagar, P. M., Sahai, A., Saklani, A., Sammour, T., Sayyed, R., Schizas, A. M. P., Schwarzkopf, E., Scripcariu, V., Selvasekar, C., Shaikh, I., Hellawell, G., Shida, D., Simpson, A., Smart, N. J., Smart, P., Smith, J. J., Solbakken, A. M., Solomon, M. J., Sørensen, M. M., Steele, S. R., Steffens, D., Stitzenberg, K., Stocchi, L., Stylianides, N. A., Sumrien, H., Sutton, P. A., Swartking, T., Taylor, C., Tekkis, P. P., Teras, J., Thurairaja, R., Toh, E. L., Tsarkov, P., Tsukada, Y., Tsukamoto, S., Tuech, J. J., Turner, W. H., Tuynman, J. B., Vasquez‐Jimenez, W., Verhoef, C., Vizzielli, G., Voogt, E. L. K., Uehara, K., Wakeman, C., Warrier, S., Wasmuth, H. H., Weber, K., Weiser, M. R., Wheeler, J. M. D., Wild, J., Wilson, M., de Wilt, J. H. W., Wolthuis, A., Yano, H., Yip, B., Yip, J., Yoo, R. N., van Zoggel, D., Winter, D. C., Kelly, M. E., Aalbers, A. G. J., Abdul Aziz, N., Abecasis, N., Abraham‐nordling, M., Akiyoshi, T., Alberda, W., Albert, M., Andric, M., Angenete, E., Antoniou, A., Auer, R., Austin, K. K., Aziz, O., Baker, R. P., Bali, M., Baseckas, G., Bebington, B., Bednarski, B. K., Beets, G. L., Berg, P. L., Beynon, J., Biondo, S., Boyle, K., Bordeianou, L., Bremers, A. B., Brunner, M., Buchwald, P., Bui, A., Burgess, A., Burger, J. W. A., Burling, D., Burns, E., Campain, N., Carvalhal, S., Castro, L., Caycedo‐marulanda, A., Chan, K. K. L., Chang, G. J., Chew, M. H., Chong, P. C., Christensen, H. K., Clouston, H., Codd, M., Collins, D., Colquhoun, A. J., Corr, A., Coscia, M., Coyne, P. E., Creavin, B., Croner, R. S., Damjanovic, L., Daniels, I. R., Davies, M., Davies, R. J., Delaney, C. P., Denost, Q., Deutsch, C., Dietz, D., Domingo, S., Dozois, E. J., Duff, M., Eglinton, T., Enrique‐navascues, J. M., Espin‐basany, E., Evans, M. D., Fearnhead, N. S., Flatmark, K., Fleming, F., Frizelle, F. A., Gallego, M. A., Garcia‐granero, E., Garcia‐sabrido, J. L., Gentilini, L., George, M. L., Ghouti, L., Giner, F., Ginther, N., Glynn, R., Golda, T., Griffiths, B., Harris, D. A., Hagemans, J. A. W., Hanchanale, V., Harji, D. P., Helewa, R. M., Heriot, A. G., Hochman, D., Hohenberger, W., Holm, T., Hompes, R., Jenkins, J. T., Kaffenberger, S., Kandaswamy, G. V., Kapur, S., Kanemitsu, Y., Kelley, S. R., Keller, D. S., Khan, M. S., Kiran, R. P., Kim, H., Kim, H. J., Koh, C. E., Kok, N. F. M., Kokelaar, R., Kontovounisios, C., Kristensen, H. Ø., Kroon, H. M., Kusters, M., Lago, V., Larsen, S. G., Larson, D. W., Law, W. L., Laurberg, S., Lee, P. J., Limbert, M., Lydrup, M. L., Lyons, A., Lynch, A. C., Mantyh, C., Mathis, K. L., Margues, C. F. S., Martling, A., Meijerink, W. J. H. J., Merkel, S., Mehta, A. M., Mcarthur, D. R., Mcdermott, F. D., Mcgrath, J. S., Malde, S., Mirnezami, A., Monson, J. R. T., Morton, J. R., Mullaney, T. G., Negoi, I., Neto, J. W. M., Nguyen, B., Nielsen, M. B., Nieuwenhuijzen, G. A. P., Nilsson, P. J., O’Connell, P. R., O’Dwyer, S. T., Palmer, G., Pappou, E., Park, J., Patsouras, D., Pellino, G., Peterson, A. C., Poggioli, G., Proud, D., Quinn, M., Quyn, A., Radwan, R. W., van Ramshorst, G. H., Rasheed, S., Rasmussen, P. C., Regenbogen, S. E., Renehan, A., Rocha, R., Rochester, M., Rohila, J., Rothbarth, J., Rottoli, M., Roxburgh, C., Rutten, H. J. T., Ryan, É. J., Safar, B., Sagar, P. M., Sahai, A., Saklani, A., Sammour, T., Sayyed, R., Schizas, A. M. P., Schwarzkopf, E., Scripcariu, V., Selvasekar, C., Shaikh, I., Hellawell, G., Shida, D., Simpson, A., Smart, N. J., Smart, P., Smith, J. J., Solbakken, A. M., Solomon, M. J., Sørensen, M. M., Steele, S. R., Steffens, D., Stitzenberg, K., Stocchi, L., Stylianides, N. A., Sumrien, H., Sutton, P. A., Swartking, T., Taylor, C., Tekkis, P. P., Teras, J., Thurairaja, R., Toh, E. L., Tsarkov, P., Tsukada, Y., Tsukamoto, S., Tuech, J. J., Turner, W. H., Tuynman, J. B., Vasquez‐jimenez, W., Verhoef, C., Vizzielli, G., Voogt, E. L. K., Uehara, K., Wakeman, C., Warrier, S., Wasmuth, H. H., Weber, K., Weiser, M. R., Wheeler, J. M. D., Wild, J., Wilson, M., de Wilt, J. H. W., Wolthuis, A., Yano, H., Yip, B., Yip, J., Yoo, R. N., van Zoggel, D., Winter, D. C., Kelly, ME, Aalbers, AGJ, Aziz, NA, Abecasis, N, Abraham-Nordling, M, Akiyoshi, T, Alberda, W, Albert, M, Andric, M, Angenete, E, Antoniou, A, Auer, R, Austin, KK, Aziz, O, Baker, RP, Bali, M, Baseckas, G, Bebington, B, Bednarski, BK, Beets, GL, Berg, PL, Beynon, J, Biondo, S, Boyle, K, Bordeianou, L, Bremers, AB, Brunner, M, Buchwald, P, Bui, A, Burgess, A, Burger, JWA, Burling, D, Burns, E, Campain, N, Carvalhal, S, Castro, L, Caycedo-Marulanda, A, Chan, KKL, Chew, GJH, Chong, PC, Christensen, HK, Clouston, H, Codd, M, Coffins, D, Colquhoun, AJ, Corr, A, Coscia, M, Coyne, PE, Creavin, B, Croner, RS, Damjanovic, L, Daniels, R, Davies, M, Davies, RJ, Delaney, CP, Denost, Q, Deutsch, C, Dietz, D, Domingo, S, Dozois, EJ, Duff, M, Eglinton, T, Enrique-Navascues, JM, Espin-Basany, E, Evans, MD, Fearnhead, NS, Flatmark, K, Fleming, F, Frizelle, FA, Gallego, MA, Garcia-Granero, E, Garcia-Sabrido, JL, Gentilini, L, George, ML, Ghouti, L, Giner, F, Ginther, N, Glynn, R, Golda, T, Griffiths, B, Harris, DA, Hagemans, JAW, Hanchanale, V, Harji, DP, Helewa, RM, Heriot, AG, Hochman, D, Hohenberger, W, Holm, T, Hompes, R, Jenkins, JT, Kaffenberger, S, Kandaswamy, GV, Kapur, S, Kanemitsu, Y, Kelley, SR, Keller, DS, Khan, MS, Kiran, RP, Kim, H, Kim, HJ, Koh, CE, Kok, NFM, Kokelaar, R, Kontovounisios, C, Kristensen, HO, Kroon, HM, Kusters, M, Lago, V, Larsen, SG, Larson, DW, Law, WL, Laurberg, S, Lee, PJ, Limbert, M, Lydrup, ML, Lyons, A, Lynch, AC, Mantyh, C, Mathis, KL, Margues, CFS, Martling, A, Meijerink, WJHJ, Merkel, S, Mehta, AM, McArthur, DR, McDermott, FD, McGrath, JS, Malde, S, Mimezami, A, Monson, JRT, Morton, JR, Mullaney, TG, Negoi, I, Neto, JWM, Nguyen, B, Nielsen, MB, Nieuwenhuijzen, GAP, Nilsson, PJ, O'Connell, PR, O'Dwyer, ST, Palmer, G, Pappou, E, Park, J, Patsouras, D, Pellino, G, Peterson, AC, Poggioli, G, Proud, D, Quinn, M, Quyn, A, Radwan, RW, van Ramshorst, GH, Rasheed, S, Rasmussen, PC, Regenbogen, SE, Renehan, A, Rocha, R, Rochester, M, Rohila, J, Rothbarth, J, Rottoli, M, Roxburgh, C, Rutten, HJT, Ryan, EJ, Safar, B, Sagar, PM, Sahai, A, Saklani, A, Sammour, T, Sayyed, R, Schizas, AMP, Schwarzkopf, E, Scripcariu, V, Selvasekar, C, Shaikh, I, Hellawell, G, Shida, D, Simpson, A, Smart, NJ, Smart, P, Smith, JJ, Solbakken, AM, Solomon, MJ, Sorensen, MM, Steele, SR, Steffens, D, Stitzenberg, K, Stocchi, L, Stylianides, NA, Sumrien, H, Sutton, PA, Swanking, T, Taylor, C, Tekkis, PP, Teras, J, Thurairaja, R, Toh, EL, Tsarkov, P, Tsukada, Y, Tsukamoto, S, Tuech, JJ, Turner, WH, Tuynman, JB, Vasquez-Jimenez, W, Verhoef, C, Vizzielli, G, Voogt, ELK, Uehara, K, Wakeman, C, Warner, S, Wasmuth, HH, Weber, K, Weiser, MR, Wheeler, JMD, Wild, J, Wilson, M, de Wilt, JHW, Wolthuis, A, Yano, H, Yip, B, Yip, J, Yoo, RN, van Zoggel, D, Winter, DC, Surgery, CCA - Cancer Treatment and quality of life, and Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Male, medicine.medical_specialty, Adolescent, Colorectal cancer, survival outcomes, medicine.medical_treatment, surgical outcome, surgical outcomes, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Interquartile range, medicine, Humans, liver metastasi, Rectal cancer, Retrospective Studies, Pelvic exenteration, business.industry, Rectal Neoplasms, Mortality rate, Liver Neoplasms, Gastroenterology, Postoperative complication, Perioperative, medicine.disease, Surgery, Pelvic Exenteration, liver metastasis, Treatment Outcome, 030220 oncology & carcinogenesis, international collaboration, Resection margin, 030211 gastroenterology & hepatology, Hepatectomy, Neoplasm Recurrence, Local, business
Abstract

Aim: At presentation, 15–20% of patients with rectal cancer already have synchronous liver metastases. The aim of this study was to determine the surgical and survival outcomes in patients with advanced rectal cancer who underwent combined pelvic exenteration and liver (oligometastatic) resection. Method: Data from 20 international institutions that performed simultaneous pelvic exenteration and liver resection between 2007 and 2017 were accumulated. Primarily, we examined perioperative outcomes, morbidity and mortality. We also assessed the impact that margin status had on survival. Results: Of 128 patients, 72 (56.2%) were men with a median age of 60 years [interquartile range (IQR) 15 years]. The median size of the liver oligometastatic deposits was 2 cm (IQR 1.8 cm). The median duration of surgery was 406 min (IQR 240 min), with a median blood loss of 1090 ml (IQR 2010 ml). A negative resection margin (R0 resection) was achieved in 73.5% of pelvic exenterations and 66.4% of liver resections. The 30-day mortality rate was 1.6%, and 32% of patients had a major postoperative complication. The 5-year overall survival for patients in whom an R0 resection of both primary and metastatic disease was achieved was 54.6% compared with 20% for those with an R1/R2 resection (P = 0.006). Conclusion: Simultaneous pelvic exenteration and liver resection is feasible, with acceptable morbidity and mortality. Simultaneous resection should only be performed where an R0 resection of both pelvic and hepatic disease is anticipated.

Published
2020

7. Histological Analyses of Capsular Contracture and Associated Risk Factors: A Systematic Review

Author

Steen Seier Poulsen, Mikkel Herly, Jens Christian Brings Jacobsen, Tim K. Weltz, Peter V Vester-Glowinski, Leonia F Rasmussen, Louise E. Rasmussen, Mathilde N. Hemmingsen, and Andreas Larsen

Subjects
medicine.medical_specialty, business.industry, Breast surgery, medicine.medical_treatment, Capsule, Histology, Capsular contracture, law.invention, Surgery, Plastic surgery, law, Metaplasia, Breast implant, Medicine, Implant, medicine.symptom, business
Abstract

Capsular contracture is a severe complication to breast surgery with implants. Previous studies suggest multiple risk factors are associated with capsular contracture, but the etiology is still unknown. We performed a literature review to investigate existing studies on histological analyses of breast implant capsules and how clinical risk factors impact the capsule morphology. The literature search was conducted in PubMed. Studies that performed histological analyses of breast implant capsules were included. Animal studies or studies with a study population of less than five patients were excluded. Fifty-two studies were included. The histological analyses showed that the breast implant capsules were organized in multiple layers with an inner layer of synovial-like metaplasia which was reported to diminish in capsules with capsular contracture. The remaining layers of the capsule mostly consisted of collagen. The alignment of the collagen fibers differed between contracted and non-contracted capsules, and capsules with higher Baker grade were generally thickest and contained more tissue inflammation. Studies investigating capsules affected by radiotherapy found a more pronounced inflammatory response and the capsules were generally thicker and fibrotic compared with nonirradiated capsules. The included studies offer valuable insights into the histological changes caused by capsular contracture and their relation to clinical risk factors. Further studies with larger sample sizes and more strict inclusion criteria are needed to further investigate implant capsules and the role of the synovial-like metaplasia for the development of capsular contracture. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 .

Published
2021

8. Intravenous supplementation type and volume are associated with 1-year outcome and major complications in patients with chronic intestinal failure

Author

Nuria Virgili, Konrad Matysiak, Cristina Cuerda, Henrik Højgaard Rasmussen, Florian Poullenot, Ronan Thibault, Umberto Aimasso, Amelia Jukes, Andre Dong Won Lee, Brooke Chapman, Geert J. A. Wanten, Simona Di Caro, Maryana Doitchinova-Simeonova, Alastair Forbes, Corrado Spaggiari, Ezra Steiger, Elena Nardi, Cécile Chambrier, Simon Lal, Paolo Orlandoni, Peter Sahin, Marina Taus, Mireille J. Serlie, Kinga Szczepanek, A. Crivelli, Nicola Wyer, Przemysław Matras, Lynn Jones, Carmen Garde, Gabriel Olveira, Marek Kunecki, José P. Suárez-Llanos, Francisca Joly, Ana Zugasti Murillo, Joanne Daniels, Loris Pironi, Zeljko Krznaric, Emma Osland, Sheldon C. Cooper, Stéphane M. Schneider, Sarah Jane Hughes, Lars Ellegård, Miriam Theilla, Luisa Masconale, Anna Zmarzly, Aurora E. Serralde-Zúñiga, André Van Gossum, Anna Simona Sasdelli, Lidia Santarpia, Nada Rotovnik Kozjek, Francesco William Guglielmi, Margie O'Callaghan, Charlene Compher, Estrella Petrina Jáuregui, Pironi, L., Steiger, E., Joly, F., Wanten, G. J. A., Chambrier, C., Aimasso, U., Sasdelli, A. S., Szczepanek, K., Jukes, A., Theilla, M., Kunecki, M., Daniels, J., Serlie, M. J., Cooper, S. C., Poullenot, F., Rasmussen, H. Ho., Compher, C. W., Crivelli, A., Hughes, S. -J., Santarpia, L., Guglielmi, F. W., Rotovnik Kozjek, N., Ellegard, L., Schneider, S. M., Matras, P., Forbes, A., Wyer, N., Zmarzly, A., Taus, M., O'Callaghan, M., Osland, E., Thibault, R., Cuerda, C., Jones, L., Chapman, B., Sahin, P., Virgili, N. M., Lee, A. D. W., Orlandoni, P., Matysiak, K., Di Caro, S., Doitchinova-Simeonova, M., Masconale, L., Spaggiari, C., Garde, C., Serralde-Zuniga, A. E., Olveira, G., Krznaric, Z., Petrina Jauregui, E., Zugasti Murillo, A., Suarez-Llanos, J. P., Nardi, E., Van Gossum, A., Lal, S., Pironi, Lori, Steiger, Ezra, Joly, Francisca, Wanten, Geert J A, Chambrier, Cecile, Aimasso, Umberto, Sasdelli, Anna Simona, Szczepanek, Kinga, Jukes, Amelia, Theilla, Miriam, Kunecki, Marek, Daniels, Joanne, Serlie, Mireille J, Cooper, Sheldon C, Poullenot, Florian, Rasmussen, Henrik Højgaard, Compher, Charlene W, Crivelli, Adriana, Hughes, Sarah-Jane, Santarpia, Lidia, Guglielmi, Francesco William, Rotovnik Kozjek, Nada, Ellegard, Lar, Schneider, Stéphane M, Matras, Przemysław, Forbes, Alastair, Wyer, Nicola, Zmarzly, Anna, Taus, Marina, O'Callaghan, Margie, Osland, Emma, Thibault, Ronan, Cuerda, Cristina, Jones, Lynn, Chapman, Brooke, Sahin, Peter, Virgili, Núria M, Lee, Andre Dong Won, Orlandoni, Paolo, Matysiak, Konrad, Di Caro, Simona, Doitchinova-Simeonova, Maryana, Masconale, Luisa, Spaggiari, Corrado, Garde, Carmen, Serralde-Zúñiga, Aurora E, Olveira, Gabriel, Krznaric, Zeljko, Petrina Jáuregui, Estrella, Zugasti Murillo, Ana, Suárez-Llanos, José P, Nardi, Elena, Van Gossum, André, Lal, Simon, University of Bologna, Cleveland Clinic, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Radboud university [Nijmegen], Hospices Civils de Lyon (HCL), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Aalborg University [Denmark] (AAU), Sahlgrenska Academy at University of Gothenburg [Göteborg], Centre Hospitalier Universitaire de Nice (CHU Nice), Medical University of Lublin, University of East Anglia [Norwich] (UEA), University Hospital Coventry, CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Hospital General Universitario 'Gregorio Marañón' [Madrid], Austin Health, Universidade de São Paulo (USP), Poznan University of Life Sciences (Uniwersytet Przyrodniczy w Poznaniu) (PULS), University College London Hospitals (UCLH), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], University of Manchester [Manchester], European Society for Clinical Nutrition and Metabolism (ESPEN)., Endocrinology, AGEM - Endocrinology, metabolism and nutrition, University of Bologna/Università di Bologna, Radboud University [Nijmegen], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Universidade de São Paulo = University of São Paulo (USP)

Subjects
Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Severity of Illness Index, Liver disease, 0302 clinical medicine, Drug Dosage Calculations, motility disorder, 2. Zero hunger, Gastroenterology, Short bowel syndrome, 3. Good health, Chronic intestinal failure, Intestines, Pharmaceutical Solutions, Venous thrombosis, Intestinal obstruction, motility disorders, Administration, Intravenous, Female, 030211 gastroenterology & hepatology, Parenteral Nutrition, Home, Adult, Fat Emulsions, Intravenous, medicine.medical_specialty, parenteral nutrition, macromolecular substances, Clinical nutrition, short bowel syndrome, 03 medical and health sciences, Cholestasis, intestinal failure, Internal medicine, medicine, Humans, 030109 nutrition & dietetics, business.industry, liver failure, medicine.disease, Intestinal Diseases, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Parenteral nutrition, Alimentació parenteral, Intestinal Absorption, Catheter-Related Infections, Parenteral feeding, Chronic Disease, Obstrucció intestinal, Fluid Therapy, business, Body mass index
Abstract

Background and aimNo marker to categorise the severity of chronic intestinal failure (CIF) has been developed. A 1-year international survey was carried out to investigate whether the European Society for Clinical Nutrition and Metabolism clinical classification of CIF, based on the type and volume of the intravenous supplementation (IVS), could be an indicator of CIF severity.MethodsAt baseline, participating home parenteral nutrition (HPN) centres enrolled all adults with ongoing CIF due to non-malignant disease; demographic data, body mass index, CIF mechanism, underlying disease, HPN duration and IVS category were recorded for each patient. The type of IVS was classified as fluid and electrolyte alone (FE) or parenteral nutrition admixture (PN). The mean daily IVS volume, calculated on a weekly basis, was categorised as 3 L/day. The severity of CIF was determined by patient outcome (still on HPN, weaned from HPN, deceased) and the occurrence of major HPN/CIF-related complications: intestinal failure-associated liver disease (IFALD), catheter-related venous thrombosis and catheter-related bloodstream infection (CRBSI).ResultsFifty-one HPN centres included 2194 patients. The analysis showed that both IVS type and volume were independently associated with the odds of weaning from HPN (significantly higher for PN 1 L/day), patients’ death (lower for FE, p=0.079), presence of IFALD cholestasis/liver failure and occurrence of CRBSI (significantly higher for PN 2–3 and PN >3 L/day).ConclusionsThe type and volume of IVS required by patients with CIF could be indicators to categorise the severity of CIF in both clinical practice and research protocols.

Published
2020

9. Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance

Author

Raluca Pais, Rachel Ostroff, Stephen Harrison, Lars Friis Mikkelsen, Elisabeth Erhardtsen, Sudha Shankar, Kimmo Porthan, Jérôme Boursier, Antonia Sinisi, Michael Kalutkiewicz, Sven Francque, Miljen Martic, Vanessa Pellegrinelli, Phil N. Newsome, Guido Hanauer, Hannele Yki-Järvinen, Rebecca Darlay, Joel Myers, Carla Yunis, Salvatore Petta, Mette Skalshøi Kjær, Pablo Ortiz, Ann K. Daly, James H. Clark, Dina Tiniakos, Yasaman Vali, Hadi Zafarmand, Matej Orešič, Maurizio Parola, Estelle Sandt, Lori L. Jennings, Matt Kelly, Tuulia Hyötyläinen, Detlef Schuppan, Céline Fournier, Chiara Rosso, Diane E. Shevell, Maria Manuela Tonini, Paul Hockings, Aidan McGlinchey, Salma Akhtar, Mette Juul Fisker, Morten A. Karsdal, Diane Whalley, Melissa R. Miller, Aldo Trylesinski, Mattias Ekstedt, Stefan Neubauer, Jeremy M. Palmer, Partho Sen, Michael Pavlides, Per Qvist, Isabel Fernández, Luca Miele, Fabio Marra, Stergios Kechagias, Richard Torstenson, Katherine Johnson, Jean-François Dufour, Elisabetta Bugianesi, M. Julia Brosnan, George V. Papatheodoridis, Kay M. Pepin, Daniel Guldager Kring Rasmussen, Henrik Landgren, Rachel Queen, Simon Cockell, Michael Allison, Patrick M.M. Bossuyt, Rocío Gallego-Durán, Christian Rosenquist, Leigh Alexander, Elizabeth Shumbayawonda, Michele Vacca, Antonio Vidal-Puig, David Wenn, Rémy Hanf, Oscar Millet, Michalina Zatorska, R. Myers, José M. Mato, Jenny Lee, Theresa Tuthill, James Twiss, Ramy Younes, Peter Leary, Lynda Doward, Kristy Wonders, Guruprasad P. Aithal, Sarah Charlton, Vlad Ratziu, Cecília M. P. Rodrigues, Christian Trautwein, Helena Cortez-Pinto, Gideon Ho, Matt J. Barter, Judith Ertle, Jörn M. Schattenberg, Maria-Magdalena Balp, Yang-Lin Liu, Clifford A. Brass, Olivier Govaere, Amalia Gastaldelli, Sergio Rodriguez Cuenca, Pierre Chaumat, Fiona Oakley, Luca Valenti, Simon J. Cockell, Saskia W.C. van Mil, Ferenc E. Mózes, Andreas Geier, Timothy Hardy, Pierre Bedossa, Andrea Dennis, Richard L. Ehman, Charlotte Erpicum, Karine Clément, Jeremy F. L. Cobbold, Christopher P. Day, Rajarshi Banerjee, Manuel Romero-Gómez, Quentin M. Anstee, Adriaan G. Holleboom, Heather J. Cordell, Kevin L. Duffin, Diana Julie Leeming, Epidemiology and Data Science, APH - Methodology, APH - Personalized Medicine, Vascular Medicine, ACS - Diabetes & metabolism, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, APH - Aging & Later Life, ARD - Amsterdam Reproduction and Development, Graduate School, Investigators, LITMUS Consortium, Johnson K., Leary P.J., Govaere O., Barter M.J., Charlton S.H., Cockell S.J., Tiniakos D., Zatorska M., Bedossa P., Brosnan M.J., Cobbold J.F., Ekstedt M., Aithal G.P., Clement K., Schattenberg J.M., Boursier J., Ratziu V., Bugianesi E., Anstee Q.M., Daly A.K., Clark J., Cordell H.J., Darlay R., Day C.P., Hardy T., Liu Y.-L., Oakley F., Palmer J., Queen R., Wonders K., Bossuyt P.M., Holleboom A.G., Zafarmand H., Vali Y., Lee J., Pais R., Schuppan D., Allison M., Cuenca S.R., Pellegrinelli V., Vacca M., Vidal-Puig A., Hyotylainen T., McGlinchey A., Oresic M., Sen P., Mato J., Millet O., Dufour J.-F., Harrison S., Neubauer S., Pavlides M., Mozes F., Akhtar S., Banerjee R., Kelly M., Shumbayawonda E., Dennis A., Erpicum C., Romero-Gomez M., Gallego-Duran R., Fernandez I., Karsdal M., Leeming D., Fisker M.J., Erhardtsen E., Rasmussen D., Qvist P., Sinisi A., Sandt E., Tonini M.M., Parola M., Rosso C., Marra F., Gastaldelli A., Francque S., Kechagias S., Yki-Jarvinen H., Porthan K., van Mil S., Papatheodoridis G., Cortez-Pinto H., Valenti L., Petta S., Miele L., Geier A., Trautwein C., Hockings P., Newsome P., Wenn D., Pereira Rodrigues C.M., Hanf R., Chaumat P., Rosenquist C., Trylesinski A., Ortiz P., Duffin K., Yunis C., Miller M., Tuthill T., Ertle J., Younes R., Alexander L., Ostroff R., Kjaer M.S., Mikkelsen L.F., Brass C., Jennings L., Balp M.-M., Martic M., Hanauer G., Shankar S., Torstenson R., Fournier C., Ehman R., Kalutkiewicz M., Pepin K., Myers J., Shevell D., Ho G., Landgren H., Myers R., Doward L., Whalley D., Twiss J., Miller, Melissa, Tuthill, Theresa, Ertle, Judith, Younes, Ramy, Alexander, Leigh, Ostroff, Rachel, Kjær, Mette Skalshøi, Mikkelsen, Lars Friis, Brass, Clifford, Jennings, Lori, Balp, Maria-Magdalena, Martic, Miljen, Hanauer, Guido, Shankar, Sudha, Torstenson, Richard, Fournier, Céline, Ehman, Richard, Kalutkiewicz, Michael, Pepin, Kay, Myers, Joel, Shevell, Diane, Ho, Gideon, Landgren, Henrik, Myers, Rob, Doward, Lynda, Whalley, Diane, Twiss, James, Clark, James, Cordell, Heather J., Darlay, Rebecca, Day, Christopher P., Hardy, Tim, Liu, Yang-Lin, Oakley, Fiona, Palmer, Jeremy, Queen, Rachel, Wonders, Kristy, Bossuyt, Patrick M., Holleboom, Adriaan G., Zafarmand, Hadi, Vali, Yasaman, Lee, Jenny, Clement, Karine, Pais, Raluca, Schuppan, Detlef, Allison, Michael, Cuenca, Sergio Rodriguez, Pellegrinelli, Vanessa, Vacca, Michele, Vidal-Puig, Antonio, Hyötyläinen, Tuulia, McGlinchey, Aidan, Orešič, Matej, Sen, Partho, Mato, Jose, Millet, Óscar, Dufour, Jean-Francois, Harrison, Stephen, Neubauer, Stefan, Pavlides, Michael, Mozes, Ferenc, Akhtar, Salma, Banerjee, Rajarshi, Kelly, Matt, Shumbayawonda, Elizabeth, Dennis, Andrea, Erpicum, Charlotte, Romero-Gomez, Manuel, Gallego-Durán, Rocío, Fernández, Isabel, Karsdal, Morten, Leeming, Diana, Fisker, Mette Juul, Erhardtsen, Elisabeth, Rasmussen, Daniel, Qvist, Per, Sinisi, Antonia, Sandt, Estelle, Tonini, Maria Manuela, Parola, Maurizio, Rosso, Chiara, Marra, Fabio, Gastaldelli, Amalia, Francque, Sven, Kechagias, Stergios, Yki-Järvinen, Hannele, Porthan, Kimmo, van Mil, Saskia, Papatheodoridis, George, Cortez-Pinto, Helena, Valenti, Luca, Petta, Salvatore, Miele, Luca, Geier, Andreas, Trautwein, Christian, Hockings, Paul, Newsome, Phil, Wenn, David, Pereira Rodrigues, Cecília Maria, Hanf, Rémy, Chaumat, Pierre, Rosenquist, Christian, Trylesinski, Aldo, Ortiz, Pablo, Duffin, Kevin, and Yunis, Carla

Subjects
SCORING SYSTEM, CPM, counts per million, AUROC, area under the receiver operating characteristic, RC799-869, AST, aspartate aminotransferase, MicroRNA, Non-alcoholic fatty liver disease, Biomarker, Sequencing, TGF-β, transforming growth factor-beta, Gastroenterology, STEATOHEPATITIS, Liver disease, 0302 clinical medicine, Fibrosis, miRNA, microRNA, logFC, log2 fold change, FIBROSIS, Immunology and Allergy, 0303 health sciences, education.field_of_study, NAS, NAFLD activity score, medicine.diagnostic_test, Fatty liver, GTEx, Genotype-Tissue Expression, Diseases of the digestive system. Gastroenterology, 3. Good health, Real-time polymerase chain reaction, Biomarker, MicroRNA, Non-alcoholic fatty liver disease, Sequencing, Liver biopsy, ACID, Biomarker (medicine), 030211 gastroenterology & hepatology, Life Sciences & Biomedicine, Research Article, EXPRESSION, medicine.medical_specialty, NAFLD, non-alcoholic fatty liver disease, NASH, non-alcoholic steatohepatitis, Population, Gastroenterology and Hepatology, SAF, steatosis–activity–fibrosis, VALIDATION, ER, endoplasmic reticulum, 03 medical and health sciences, cDNA, complementary DNA, Internal medicine, ALT, alanine aminotransferase, Gastroenterologi, Internal Medicine, medicine, NAFL, non-alcoholic fatty liver, ALGORITHM, FIB-4, fibrosis-4, education, 030304 developmental biology, PCA, principal component analysis, Science & Technology, Gastroenterology & Hepatology, Hepatology, business.industry, FC, fold change, medicine.disease, digestive system diseases, FLIP, fatty liver inhibition of progression, Ct, cycle threshold, Steatosis, qPCR, quantitative PCR, business
Abstract

Background & Aims Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages. Methods We profiled 2,083 serum miRNAs in a discovery cohort (183 cases with NAFLD representing the complete NAFLD spectrum and 10 population controls). miRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional cases with NAFLD and 15 population controls by quantitative reverse transcriptase PCR. Results Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages, but miR-193a-5p consistently showed increased levels in all comparisons. Relative to NAFL/non-alcoholic steatohepatitis (NASH) with mild fibrosis (stage 0/1), 3 miRNAs (miR-193a-5p, miR-378d, and miR378d) were increased in cases with NASH and clinically significant fibrosis (stages 2–4), 7 (miR193a-5p, miR-378d, miR-378e, miR-320b, miR-320c, miR-320d, and miR-320e) increased in cases with NAFLD activity score (NAS) 5–8 compared with lower NAS, and 3 (miR-193a-5p, miR-378d, and miR-378e) increased but 1 (miR-19b-3p) decreased in steatosis, activity, and fibrosis (SAF) activity score 2–4 compared with lower SAF activity. The significant findings for miR-193a-5p were replicated in the additional cohort with NAFLD. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n = 80); liver GPX8 levels correlated positively with serum miR-193a-5p. Conclusions Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD. Lay summary MicroRNAs (miRNAs) are small pieces of nucleic acid that may turn expression of genes on or off. These molecules can be detected in the blood circulation, and their levels in blood may change in liver disease including non-alcoholic fatty liver disease (NAFLD). To see if we could detect specific miRNA associated with advanced stages of NAFLD, we carried out miRNA sequencing in a group of 183 patients with NAFLD of varying severity together with 10 population controls. We found that a number of miRNAs showed changes, mainly increases, in serum levels but that 1 particular miRNA miR-193a-5p consistently increased. We confirmed this increase in a second group of cases with NAFLD. Measuring this miRNA in a blood sample may be a useful way to determine whether a patient has advanced NAFLD without an invasive liver biopsy., Graphical abstract, Highlights • Serum miRNA was sequenced in 183 NAFLD cases of varying severity and 10 population controls. • Plasma levels of miR-193a-5p were significantly increased in patients with advanced fibrosis, high NAS scores, or high SAF scores. • Other miRNAs including miR378d and miR378e were also significantly increased in certain comparisons. • The findings for miR-193a-5p were replicated in a cohort of 372 additional NAFLD cases.

Published
2022

10. Low arthroplasty survival after treatment for proximal humerus fracture sequelae:3,245 shoulder replacements from the Nordic Arthroplasty Register Association

Author

Björn Salomonsson, Sigrid Rasmussen, Yilmaz Demir, Steen Lund Jensen, Anne Marie Fenstad, Randi Hole, Inger Mechlenburg, Ville Äärimaa, Ditte Unbehaun, Jeppe V. Rasmussen, and Stig Brorson

Subjects
030222 orthopedics, medicine.medical_specialty, Proximal humerus, business.industry, medicine.medical_treatment, Reverse shoulder, General Medicine, Cumulative survival, Arthroplasty, Surgery, 03 medical and health sciences, lcsh:RD701-811, 0302 clinical medicine, lcsh:Orthopedic surgery, Median time, medicine, Orthopedics and Sports Medicine, In patient, 030212 general & internal medicine, business, After treatment
Abstract

Background and purpose — Proximal humerus fractures (PHF) may result in sequelae indicating arthroplasty. We report cumulative survival rates and reasons for revision after arthroplasty for proximal humerus fracture sequelae (PHFS). Patients and methods — Data were derived from the Nordic Arthroplasty Register Association. The Kaplan–Meier method was used to illustrate survival rates. A scaled Schoenfeld residual plot was used to report the risk of revision for men relative to women in patients who were treated with reverse shoulder arthroplasty (RSA). Revision was defined as removal or exchange of any component or the addition of a glenoid component. Results — 30,190 primary arthroplasties were reported from 2004 to 2016, of which 3,245 were for PHFS. The estimated 1-, 5-, and 10-year cumulative survival rates (95% CI) were 96% (95–97), 90% (89–92), and 86% (83–88) for stemmed hemiarthroplasty and 94% (92–95), 89% (87–91), and 86% (82–90) for RSA with a median time to revision of 18 months (IQR 9–44) and 3 months (IQR 0–17). The risk of revision for men relative to women in patients who were treated with RSA was 3.2 (1.9–5.1) 0–1 year after surgery and 1.9 (0.9–4.1) 1–8 years after surgery. The estimated 1-, 5-, and 10-year cumulative survival rates (95% CI) were 94% (92–96), 88% (85–90), and 80% (75–86) for men and 95% (94–96), 86% (84–89), and 81% (77–84) for young patients. Interpretation — Shoulder arthroplasty for PHFS was associated with lower survival rates, compared with previously published results of shoulder arthroplasty for acute PHF. The low arthroplasty survival rates for men and young patients especially are worrying.

Published
2022

11. An update on COVID-19 and pregnancy

Author

Denise J. Jamieson and Sonja A. Rasmussen

Subjects
medicine.medical_specialty, COVID-19 Vaccines, Coronavirus Disease 2019 (COVID-19), perinatal infection, Disease, Severity of Illness Index, Preeclampsia, law.invention, Pre-Eclampsia, Pregnancy, Risk Factors, newborn, law, medicine, Humans, pneumonia, Healthcare Disparities, Pregnancy Complications, Infectious, Risk factor, Adverse effect, Fetus, SARS-CoV-2, Obstetrics, business.industry, COVID-19, preterm birth, Obstetrics and Gynecology, Stillbirth, medicine.disease, Intensive care unit, Infectious Disease Transmission, Vertical, fetus, maternal death, Premature Birth, Female, vertical transmission, Maternal death, Disease Susceptibility, fetal death, Expert Review, business
Abstract

Physiologic, mechanical and immunologic alterations in pregnancy could potentially affect susceptibility to and severity of COVID-19 during pregnancy. Due to lack of comparable incidence data and challenges with disentangling differences in susceptibility from different exposure risks, data are insufficient to determine whether pregnancy increases susceptibility to SARS-CoV-2 infection. Data support pregnancy as a risk factor for severe disease associated with COVID-19; some of the best evidence comes from the Centers for Disease Control and Prevention’s (CDC’s) COVID-19 surveillance system, which reported that pregnant persons were more likely to be admitted to an intensive care unit (ICU), require invasive ventilation, require extracorporeal membrane oxygenation, and die compared with nonpregnant women of reproductive age. Although intrauterine transmission of SARS-CoV-2 has been documented, it appears to be rare, possibly related to low levels of SARS-CoV-2 viremia and decreased co-expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) needed for SARS-CoV-2 entry into cells in the placenta. Evidence is accumulating that SARS-CoV-2 infection during pregnancy is associated with a number of adverse pregnancy outcomes including preeclampsia, preterm birth, and stillbirth, especially among pregnant persons with severe COVID-19 disease. In addition to the direct impact of COVID-19 on pregnancy outcomes, there is evidence that the pandemic and its effects on healthcare systems have had adverse effects on pregnancy outcomes, such as increased stillbirths and maternal deaths. These trends may represent widening disparities and an alarming reversal of recent improvements in maternal and infant health. All three COVID-19 vaccines currently available under an Emergency Use Authorization by the United States Food and Drug Administration can be administered to pregnant or lactating persons, with no preference for vaccine type. Although safety data in pregnancy are rapidly accumulating and no safety signals in pregnancy have been detected, additional information about birth outcomes, particularly among persons vaccinated earlier in pregnancy, are needed.

Published
2022

12. An evaluation of interventions to improve outcomes for hospitalized patients in isolation: A systematic review

Author

Bodil Rasmussen, Olumuyiwa Omonaiye, Anastasia Hutchinson, Robin Digby, Trisha Dunning, Debra Berry, Alison M. Hutchinson, Julie Considine, Elizabeth Manias, Sharon F Kramer, and Tracey Bucknall

Subjects
Adult, medicine.medical_specialty, Music therapy, Adolescent, Isolation (health care), Epidemiology, MEDLINE, Psychological intervention, PsycINFO, law.invention, Young Adult, Randomized controlled trial, Quality of life, law, medicine, Humans, Child, Exercise, Aged, business.industry, Health Policy, Clinical study design, Public Health, Environmental and Occupational Health, Middle Aged, Infectious Diseases, Child, Preschool, Quality of Life, Physical therapy, business
Abstract

Background Isolation is effective in preventing transmission of infectious disease. However, it has been shown to have negative effects including increased anxiety and poor physical outcomes. Objectives To summarize the effects of interventions to improve safety and outcomes for patients in isolation Design Systematic review (PROSPERO protocol registration - CRD42020222779). Setting Acute hospital Participants Intervention studies including patients in preventative or protective isolation in a single room. Methods MEDLINE, Global Health, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and Excerpta Medica database were searched from 1996-October 2020. Two independent reviewers screened references and assessed risk of bias. One reviewer extracted data and was checked by another. Main outcomes were Quality of Life and mortality. Results We identified 16,698 references and included 6 studies with different study designs. Average age ranged from 4-71 years. Samples sizes were small (range 10-49 participants) apart from one non-randomized controlled trial including >600 participants. Interventions were music therapy (n = 3), psychological counseling (n = 2) and exercise training (n = 1). One study reporting on Quality of Life and found no change after exercise. None of the studies reported on mortality. Due to heterogeneous results no meta-analyses were performed. Conclusions There is a lack of high-quality evidence for effective comprehensive interventions to manage adverse effects associated with isolation. Future studies should investigate the effect of multi-component interventions using rigorous methods to improve outcomes for hospitalized isolated patients.

Published
2022

13. Mesenteric Lymphadenitis and Terminal Ileitis is Associated With Yersinia Infection: A Meta-analysis

Author

Tilde Rasmussen, Barbara Juliane Holzknecht, Jacob Rosenberg, Amanda Brunchmann, and Siv Fonnes

Subjects
Mesenteric Lymphadenitis, medicine.medical_specialty, Yersinia Infections, biology, business.industry, Mesenteric lymphadenitis, Disease, Appendix, Yersinia, Appendicitis, biology.organism_classification, medicine.disease, Gastroenterology, Crohn Disease, Meta-analysis, Internal medicine, Humans, Medicine, Yersinia pseudotuberculosis, Surgery, Ileitis, business, Yersinia enterocolitica
Abstract

Background Yersinia infection affects terminal ileum and lymph nodes and could therefore mimic the symptoms of appendicitis. We aimed to systematically characterise the suspected or confirmed abdominal diseases and/or surgeries associated with Yersinia infection. Materials and methods This systematic review and meta-analysis was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A protocol (CRD42016053252) was uploaded to PROSPERO. The searches were conducted in PubMed and EMBASE on October 2, 2020. Original reports on patients with abdominal surgical diseases were included. The primary outcome was to characterise suspected or confirmed abdominal surgical diseases and/or surgeries associated with Yersinia infection, while the secondary outcomes were the positive rate of Yersinia species for each disease and surgery, and to investigate the rate of Yersinia spp. in different geographic regions. We calculated the weighted mean prevalence of positive tests for Yersinia spp. for the different diseases and surgeries according to the detection method and for subgroups based on geographic region. Results From the search, 33 studies were included in the systematic review and 18 in the meta-analysis. Across geographic regions, the weighted mean prevalence for Yersinia spp. was 51% (95% CI 34%-69%) in mesenteric lymphadenitis, 65% (95% CI 45%-85%) in terminal ileitis, and 8% (95% CI 2%-15%) in normal appendices. Conclusions Around half of the patients with mesenteric lymphadenitis and terminal ileitis were serologically positive for infections with Yersinia spp. Yersinia infection may cause unnecessary surgery for suspected appendicitis due to symptoms from mesenteric lymphadenitis or terminal ileitis.

Published
2022

14. Good long-term patient-reported outcome after shoulder arthroplasty for cuff tear arthropathy

Author

Karoline P. Nielsen, Alexander Amundsen, Bo Sanderhoff Olsen, and Jeppe V. Rasmussen

Subjects
medicine.medical_specialty, medicine.medical_treatment, Reverse shoulder, Osteoarthritis, Diseases of the musculoskeletal system, Long-term, Medicine, Orthopedics and Sports Medicine, Significant risk, Patient-reported outcome, Orthopedic surgery, business.industry, Treatment options, medicine.disease, Arthroplasty, Surgery, Reverse shoulder arthroplasty, Rotator cuff arthropathy, RC925-935, Observational study, Hemiarthroplasty, Cuff Tear Arthropathy, business, RD701-811
Abstract

Background: The use of the reverse shoulder arthroplasty (RSA) for cuff tear arthropathy (CTA) has increased within the last decades, but there is still limited information about the long-term outcome and how it performs in comparison with hemiarthroplasty (HA). The aim of this study was to compare the long-term patient-reported outcomes of RSA and HA for CTA. Methods: We included all patients with CTA, who according to the Danish Shoulder Arthroplasty Registry, underwent either HA or RSA between 2006 and 2010. Patients who were alive were sent the Western Ontario Osteoarthritis of the Shoulder (WOOS) questionnaire in 2020. One hundred twenty (65%) patients returned a complete questionnaire. The linear regression model was used to compare RSA and HA. Sex, age, and previous surgery were included in the multivariable model. Results: Forty-two HAs and 78 RSAs were evaluated with a mean follow-up time of 11.5 and 10.6 years, respectively. The mean WOOS score was 66.7 for HA and 71.7 for RSA. The difference of 5.0 was neither statistically significant nor clinically important (95% confidence interval: -4.3 to 14.2, P = .17), nor were there any significant risk of a worse WOOS score for sex, age, or previous surgery. Conclusion: To our knowledge, this is the first study to compare the long-term patient-reported outcomes of HA and RSA for CTA. Our results indicate that RSA is a reliable and durable treatment option for CTA with good long-term results. Based on this observational study, it is not possible to make safe estimates about the effect of RSA compared with HA, but similar to RSA, HA was associated with relatively good long-term results.

Published
2022

15. Biomarkers of Cerebral Injury for Prediction of Postoperative Cognitive Dysfunction in Patients Undergoing Cardiac Surgery

Author

Kaj Blennow, Lars S. Rasmussen, Jens-Christian Nilsson, Christian Hassager, Henrik Zetterberg, Michael Wanscher, Jesper Kjaergaard, Anne G. Vedel, Frederik Holmgaard, Sebastian Wiberg, and Anne Langkilde

Subjects
medicine.medical_specialty, 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Postoperative Cognitive Complications, Aortic valve replacement, Randomized controlled trial, 030202 anesthesiology, law, Cardiopulmonary bypass, Humans, Medicine, Cognitive Dysfunction, Cardiac Surgical Procedures, Coronary Artery Bypass, Receiver operating characteristic, business.industry, medicine.disease, Confidence interval, Cardiac surgery, Anesthesiology and Pain Medicine, Brain Injuries, Anesthesia, Biomarker (medicine), Cardiology and Cardiovascular Medicine, business, Postoperative cognitive dysfunction, Biomarkers
Abstract

Objectives To assess the ability of the biomarkers neuron-specific enolase (NSE), tau, neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP) to predict postoperative cognitive dysfunction (POCD) at discharge in patients who underwent cardiac surgery. Design Post hoc analyses (with tests being prespecified before data analyses) from a randomized clinical trial. Setting Single-center study from a primary heart center in Denmark. Participants Adult patients undergoing elective or subacute on-pump coronary artery bypass grafting and/or aortic valve replacement. Interventions Blood was collected before induction of anesthesia, after 24 hours, after 48 hours, and at discharge from the surgical ward. The International Study of Postoperative Cognitive Dysfunction test battery was applied to diagnose POCD at discharge and after three months. Linear mixed models of covariance were used to assess whether repeated measurements of biomarker levels were associated with POCD. Receiver operating characteristic (ROC) curves were applied to assess the predictive value of each biomarker measurement for POCD. Measurements and Main Results A total of 168 patients had biomarkers measured at baseline, and 47 (28%) fulfilled the POCD criteria at discharge. Patients with POCD at discharge had significantly higher levels of tau (p = 0.02) and GFAP (p = 0.01) from baseline to discharge. The biomarker measurements achieving the highest area under the ROC curve for prediction of POCD at discharge were NFL measured at discharge (AUC, 0.64; 95% confidence interval [CI], 0.54-0.73), GFAP measured 48 hours after induction (AUC, 0.64; 95% CI, 0.55-0.73), and GFAP measured at discharge (AUC, 0.64; 95% CI, 0.54-0.74), corresponding to a moderate predictive ability. Conclusions Postoperative serum levels of tau and GFAP were significantly elevated in cardiac surgery patients with POCD at discharge, however, the biomarkers achieved only modest predictive abilities for POCD at discharge. Postoperative levels of NSE were not associated with POCD at discharge.

Published
2022

16. Tumor mutational burden and purity adjustment before and after treatment with temozolomide in 27 paired samples of glioblastoma: a prospective study

Author

Joachim Weischenfeldt, Hans Skovgaard Poulsen, Petra Hamerlik, Olga Østrup, Christina Westmose Yde, Aidan Flynn, Jannick Brennum, Dorte Schou Nørøxe, Finn Cilius Nielsen, Ulrik Lassen, and Jane Skjøth-Rasmussen

Subjects
Oncology, Cancer Research, medicine.medical_specialty, tumor purity, tumor mutational burden, medicine.medical_treatment, temozolomide, Internal medicine, immune therapy, Biomarkers, Tumor, Genetics, medicine, Humans, Clinical significance, Prospective Studies, Prospective cohort study, paired samples, Research Articles, RC254-282, Mutation Spectra, Temozolomide, business.industry, glioblastoma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, General Medicine, Immune checkpoint, Tumor Burden, Radiation therapy, Isocitrate dehydrogenase, CpG site, Mutation, Molecular Medicine, Neoplasm Recurrence, Local, business, Research Article, medicine.drug
Abstract

Treatment of glioblastoma (GBM) remains a challenging task, with limited treatment options, none offering a cure. Immune therapy has proven effective across different cancers with remarkable response rates. Tumor mutational burden (TMB) is a marker of response, but technical and methodological differences in TMB estimates have made a proper assessment and comparison challenging. Here, we analyzed a prospective collection of paired samples from 35 patients with newly diagnosed GBM, all of whom were wild‐type (WT) for isocitrate dehydrogenase, before and after treatment with radiotherapy and temozolomide. Seven patients (20%) had O6‐methylguanine‐DNA methyltransferase‐methylated tumors. Six patients (17%) had two relapse surgeries, and tissue from all three surgeries was collected. We found that accurate evaluation of TMB was confounded by high variability in the cancer cell fraction of relapse samples. To ameliorate this, we developed a model to adjust for tumor purity based on the relative density distribution of variant allele frequencies in each primary–relapse pair. Additionally, we examined the mutation spectra of shared and private mutations. After tumor purity adjustment, we found TMB comparison reliable in tumors with tumor purity between 15% and 40%, resulting in 27/35 patients (77.1%). TMB remained unchanged from 0.65 mutations per megabase (Mb) to 0.67/Mb before and after treatment, respectively. Examination of the mutation spectra revealed a dominance of C > T transitions at CpG sites in both shared and relapse‐private mutations, consistent with cytosine deamination and the clock‐like mutational signature 1. We present and apply a cellularity correction approach that enables more accurate assessment of TMB in paired tumor samples. We did not find a significant increase in TMB after correcting for cancer cell fraction. Our study raises significant concerns when determining TMB. Although a small sample size, corrected TMB can have a clinical significance when stratifying patients to experimental treatment, for example, immune checkpoint therapy., Tumor mutational burden (TMB) is an important clinical marker used to potentially allocate patients for immune therapy. We estimated TMB before and after treatment in 35 paired samples from patients with glioblastoma. Surprisingly, relapse samples presented with a low degree of tumor purity, making intersampling comparison of TMB unreliable. We therefore developed a computational method to adjust for tumor purity in exome sequencing data and found comparison reliable in 27 paired samples. The underexplored role of tumor purity should be included in the development of a standardized method for TMB evaluation in order to stratify clinical data analysis and the evaluation of cancer treatment strategies.

Published
2022

17. Association of Clear Cell Likelihood Score on MRI and Growth Kinetics of Small Solid Renal Masses on Active Surveillance

Author

Robert G. Rasmussen, R. Carson Sibley, Jeffrey A. Cadeddu, Yin Xi, Christopher J. Lee, and Ivan Pedrosa

Subjects
Male, Oncology, medicine.medical_specialty, Growth kinetics, MEDLINE, Kidney, Renal cell carcinoma, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Watchful Waiting, Association (psychology), Carcinoma, Renal Cell, Aged, Probability, Retrospective Studies, business.industry, General Medicine, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Kidney Neoplasms, Disease Progression, Female, business, Clear cell
Abstract

Please see the Editorial Comment by Sanjay Sharma discussing this article. To listen to the podcast associated with this article, please select one of the following: iTunes, Google Play, or direct ...

Published
2022

18. Biopsychosocial Rehabilitation for Inflammatory Arthritis and Osteoarthritis Patients: A systematic review and meta-analysis of randomized trials

Author

Carsten Bogh Juhl, Sabrina Mai Nielsen, Robin Christensen, Rinie Geenen, Berit Schiøttz-Christensen, Peter Thinggaard, Morten B Pedersen, Philip G. Conaghan, Kirstine Amris, Maarten de Wit, Anne Faber Hansen, Lyn March, Simon Tarp, Philip J. Mease, Lee S. Simon, Ernest Choy, and Marianne U Rasmussen

Subjects
Biopsychosocial model, medicine.medical_specialty, medicine.medical_treatment, MEDLINE, law.invention, Findings tables, Randomized controlled trial, Quality of life, Outpatient care, Rheumatology, law, Rheumatoid-arthritis, Educational-program, Medicine, Adverse effect, Global burden, Rehabilitation, Hip, business.industry, Ankylosing-spondylitis, Multidisciplinary team care, Management, Meta-analysis, Physical therapy, Patient-reported outcome, Knee osteoarthritis, business
Abstract

Objective: To assess the benefits and harms associated with biopsychosocial rehabilitation in patients with inflammatory arthritis and osteoarthritis (OA). Methods: We performed a systematic review and meta-analysis. Data were collected through electronic searches of Cochrane CENTRAL, MEDLINE, Embase, PsycInfo, and CINAHL databases up to March 2019. Trials examining the effect of biopsychosocial rehabilitation in adults with inflammatory arthritis and/or OA were considered eligible, excluding rehabilitation adjunct to surgery. The primary outcome for benefit was pain and total withdrawals for harm. Results: Of the 27 trials meeting the eligibility criteria, 22 trials (3,750 participants) reported sufficient data to be included in the quantitative synthesis. For patient-reported outcome measures, biopsychosocial rehabilitation was slightly superior to control for pain relief (standardized mean difference [SMD] −0.19 [95% confidence interval (95% CI) −0.31, –0.07]), had a small effect on patient global assessment score (SMD –0.13 [95% CI –0.26, –0.00]), with no apparent effect on health-related quality of life, fatigue, self-reported disability/physical function, mental well-being, and reduction in pain intensity ≥30%. Clinician-measured outcomes displayed a small effect on observed disability/physical function (SMD −0.34 [95% CI −0.57, −0.10]), a large effect on physician global assessment score (SMD −0.72 [95% CI −1.18, −0.26]), and no effect on inflammation. No difference in harms existed in terms of the number of withdrawals, adverse events, or serious adverse events. Conclusion: Biopsychosocial rehabilitation produces a significant but clinically small beneficial effect on patient-reported pain among patients with inflammatory arthritis and OA, with no difference in harm. Methodologic weaknesses were observed in the included trials, suggesting low-to-moderate confidence in the estimates of effect.

Published
2023

19. Icosapent Ethyl Reduces Ischemic Events in Patients With a History of Previous Coronary Artery Bypass Grafting: REDUCE-IT CABG

Author

Subodh Verma, Deepak L. Bhatt, Ph. Gabriel Steg, Michael Miller, Eliot A. Brinton, Terry A. Jacobson, Nitish K. Dhingra, Steven B. Ketchum, Rebecca A. Juliano, Lixia Jiao, Ralph T. Doyle, Craig Granowitz, C. Michael Gibson, Duane Pinto, Robert P. Giugliano, Matthew J. Budoff, R. Preston Mason, Jean-Claude Tardif, Christie M. Ballantyne, Fabrice M.A.C. Martens, Astrid Schut, Brian Olshansky, Mina Chung, Al Hallstrom, Lesly Pearce, Cyrus Mehta, Rajat Mukherjee, Anjan K. Chakrabarti, Eli V. Gelfand, Megan Carroll Leary, Duane S. Pinto, Yuri B. Pride, Steven Ketchum, Ramakrishna Bhavanthula, Gertrude Chester, Christina Copland, Katelyn Diffin, Ralph Doyle, Kurt Erz, Alex Giaquinto, Paula Glanton, Angela Granger, Richard H. Iroudayassamy, Rebecca Juliano, James Jin, Dimitry Klevak, Hardik Panchal, Robert Wang, Shin-Ru Wang, Gerard Abate, Peggy J. Berry, Rene Braeckman, Declan Doogan, Anne Elson, Amy HauptmannBaker, Isabel Lamela, Catherine Lubeck, Mehar Manku, Sabina Murphy, Monica Sanford, William Stirtan, Paresh Soni, Arnaud Bastien, Demetria Foster, Evangelito Gascon, Judith Johnson, Lasbert Latona, Gang Liu, Sandra Palleja, Nelly Sanjuan, Jimmy Shi, William Stager, Mukund Venkatakrishnan, Ahmed Youssef-Agha, Julie Zhu, Leela Aertker, Suresh Ankolekar, Lisa Goldberg, Natasa Rajicic, Jianfen Shu, Heng Zou, Magdy Mikhail, Gamil Dawood, N. Mathew Koshy, Sandip K. Mukherjee, Rafik Abadier, Andrea L. Lawless, William P. McGuinn, Howard Weintraub, Kathryn Rohr, Edmund Claxton, Robert J. Weiss, Terry D. Klein, Mani Nallasivan, Stephen Crowley, Marilyn King, Anthony D. Alfieri, David Fitz-Patrick, Irving Loh, Nolan J. Mayer, Rakesh Prashad, Samuel Lederman, Debra Weinstein, Harold E. Bays, Keith Chu, Alireza Maghsoudi, Paul D. Thompson, Jeff Carstens, Anna Chang, Kenneth R. Cohen, Julius Dean, Howard S. Ellison, Bernard Erickson, Enrique A. Flores, Daniel W. Gottlieb, Paul Grena, John R. Guyton, Peter H. Jones, John M. Joseph, Norman E. Lepor, Sam Lerman, Robert D. Matheney, Theodore R. Pacheco, Michael B. Russo, John Rubino, Edward S. Pereira, Albert A. Seals, Eduardo Viera, Alan D. Steljes, Jason Thompson, Shaival Kapadia, Michael McIvor, Jorge E. Salazar, Jose O. Santiago, Ralph Vicari, Martin R. Berk, William A. Kaye, Marcus McKenzie, David Podlecki, Brian D. Snyder, Stephen Nash, David M. Herrington, Wallace Johnson, Joseph R. Lee, Ronald Blonder, Alpa M. Patel, Ramon Castello, Susan Greco, Dean J. Kereiakes, Venkatesh K. Nadar, Mark Nathan, Ranganatha P. Potu, Robert Sangrigoli, Richard Smalling, Mitchell Davis, Robert Braastad, James McCriskin, Kunal Bodiwala, Joe L. Hargrove, Mark W. Graves, George Emlein, Raegan W. Durant, James W. Clower, Rohit Arora, Narendra Singh, Lisa Warsinger Martin, W Herbert Haught, Marc P. Litt, Michael D. Klein, Peter Hoagland, Michael Goldstein, Marco S. Mazzella, Daniel H. Dunker, Brian H. Kahn, Carlos S. Ince, Frank A. McGrew, Jay Lee, David Pan, Salman A. Khan, Uri Elkayam, Wasim Deeb, Anne C. Goldberg, Christopher S. Brown, Wayne N. Leimbach, Thomas S. Backer, David R. Sutton, Joel Gellman, Anu R. George, Alan S. Hoffman, Mark Kates, Kishlay Anand, Robert Bear, Brendan J. Cavanaugh, Ramon G. Reyes, Rodolfo Sotolongo, Kenneth Sabatino, Kevin Gallagher, Ehab Sorial, Chris Geohas, Kathleen E. Magness, Bernard P. Grunstra, Frederik A. Martin, William S. Knapp, Mel E. Lucas, John J. Champlin, Jason Demattia, Patrick H. Peters, Judith Kirstein, William J. Randall, Cezar S. Staniloae, Jennifer G. Robinson, Alexander Adler, Christopher Case, Andrew J. Kaplan, Gregory F. Lakin, Krishan K. Goyle, Michael J. DiGiovanna, Chester L. Fisher, Michael Lillestol, Michael Robinson, Robert G. Perry, Lawrence S. Levinson, Brian G. Everhart, Robert D. Madder, Earl F. Martin, Earl E. Martin, Imtiaz Alam, Jose Mari L. Elacion, Robina Poonawala, Taddese T. Desta, Jerome A. Robinson, Gilbert J. Martinez, Jakkidi S. Reddy, Jeffrey D. Wayne, Samuel Mujica Trenche, Westbrook I. Kaplan, Rubin H. Saavedra, Michael D. DiGregorio, Barry D. Bertolet, Neil J. Fraser, Terence T. Hart, Ronald J. Graf, David A. Jasper, Michael Dunn, Dan A. Streja, David J. Strobl, Nan Jiang, Vicki Kalen, Richard Mascolo, Mercedes B. Samson, Michael Stephens, Bret M. Bellard, Mario Juarez, Patrick J. McCarthy, John B. Checton, Michael Stillabower, Edward Goldenberg, Amin H. Karim, Naseem Jaffrani, Robert C. Touchon, Erich R. Fruehling, Clayton J. Friesen, Pradipta Chaudhuri, Frank H. Morris, Robert E. Broker, Rajesh J. Patel, Susan Hole, Randall P. Miller, Francisco G. Miranda, Sadia Dar, Shawn N. Gentry, Paul Hermany, Charles B. Treasure, Miguel E. Trevino, Raimundo Acosta, Anthony Japour, Samuel J. Durr, Thomas Wang, Om P. Ganda, Perry Krichmar, James L. Arter, Douglas Jacoby, Michael A. Schwartz, Amer Al-Karadsheh, Nelson E. Gencheff, John A. Pasquini, Richard Dunbar, Sarah Kohnstamm, Hector F. Lozano, Francine K. Welty, Thomas L. Pitts, Brian Zehnder, Salah El Hafi, Mark A. King, Arnold Ghitis, Marwan M. Bahu, Hooman Ranjbaran Jahromi, Ronald P. Caputo, Robert S. Busch, Michael D. Shapiro, Suhail Zavaro, Munib Daudjee, Shahram Jacobs, Vipul B. Shah, Frank Rubalcava, Mohsin T. Alhaddad, Henry Lui, Raj T. Rajan, Fadi E. Saba, Mahendra Pai N Gunapooti, Tshiswaka B. Kayembe, Timothy Jennings, Robert A. Strzinek, Michael H. Shanik, Pradeep K. Singh, Alastair C. Kennedy, Howard Rubenstein, Ramin Manshadi, Joanne Ladner, Lily Kakish, Ashley Kakish, Amy L. Little, Jaime Gerber, Nancy J. Hinchion, Janet Guarino, Denise Raychok, Susan Budzinski, Kathleen Kelley-Garvin, April Beckord, Jessica Schlinder, Arthur Schwartzbard, Stanley Cobos, Deborah Freeman, David Abisalih, Dervilla McCann, Kylie Guy, Jennifer Chase, Stacey Samuelson, Madeline Cassidy, Marissa Tardif, Jaime Smith, Brenna Sprout, Nanette Riedeman, Julie Goza, Lori Johnson, Chad Kraske, Sheila Hastings, Chris Dutka, Stephanie Smith, Toni McCabe, Kathleen Maloney, Paul Alfieri, Vinay Hosemane, Chanhsamone Syravanh, Cindy Pau, April Limcoiloc, Tabitha Carreira, Taryn S. Kurosawa, Razmig Krumian, Krista Preston, Ashraf Nashed, Daria Schneidman-Fernandez, Jack Patterson, John Tsakonas, Jennifer Esaki, Lynn Sprafka, Porous Patel, Brian Mitchell, Erin M. Ross, Donna Miller, Akash Prashad, Kristina M. Feyler, Natasha Juarbe, Sandra Herrera, Sarah M. Keiran, Becky Whitehead, Whitney Asher, Coury Hobbs, Abbey Elie, Jean Brooks, Amanda L. Zaleski, Brenda Foxen, Barb Lapke, Philippa Wright, Bristol Pavol, Gwen Carangi, Marla Turner, Katharine W. Sanders, Rikita S. Delamar, Virginia L. Wilson, Sarah M. Harvel, Alison M. Cartledge, Kaitlyn R. Bailey, Kathleen Mahon, Timothy Schuchard, Jen Humbert, Mark C. Hanson, Michael P. Cecil, James S. Abraham, Lorie Benedict, Claudia Slayton, Curtis S. Burnett, Rachel W. Ono-Lim, Sharon Budzinski, Shubi A. Khan, Sharon Goss, Terry Techmanski, Farida Valliani, Rimla Joseph, Edith Flores, Laurn Contreras, Ana Aguillon, Carrie-Ann Silvia, Maria Martin, Edmund K. Kerut, Leslie W. Levenson, Louis B. Glade, Brian J. Cospolich, Maureen W. Stein, Stephen P. LaGuardia, Thelma L. Sonza, Tracy M. Fife, Melissa Forschler, Jasmyne Watts, Judy Fritsch, Emese Futchko, Sarah Utech, Scott B. Baker, Miguel F. Roura, Scott A. Segel, James S. Magee, Cathy Jackson, Rebecca F. Goldfaden, Liudmila Quas, Elizabeth C. Ortiz, Michael Simpson, Robert Foster, Christopher Brian, James Trimm, Michael Bailey, Brian Snoddy, Van Reeder, Rachel Wilkinson, Harold Settle, Cynthia Massey, Angela Maiola, Michele Hall, Shelly Hall, Wanda Hall, Mark Xenakis, Janet Barrett, Giovanni Campanile, David Anthou, Susan F. Neill, Steven Karas, Enrique Polanco, Norberto Schechtman, Grace Tischner, Kay Warren, Cynthia St Cyr, Menna Kuczinski, Latrina Alexander, Maricruz Ibarra, Barry S. Horowitz, Jaime Steinsapir, Jeanette Mangual-Coughlin, Brittany Mooney, Precilia Vasquez, Kathleen Rodkey, Alexandria Biberstein, Christine Ignacio, Irina Robinson, Marcia Hibberd, Lisa B. Hoffman, Daniel J. Murak, Raghupathy Varavenkataraman, Theresa M. Ohlson Elliott, Linda A. Cunningham, Heather L. Palmerton, Sheri Poole, Jeannine Moore, Helene Wallace, Ted Chandler, Robert Riley, Farah Dawood, Amir Azeem, Michael Cammarata, Ashleigh Owen, Shivani Aggarwal, Waqas Qureshi, Mohamed Almahmoud, Abdullahi Oseni, Adam Leigh, Erin Barnes, Adam Pflum, Amer Aladin, Karen Blinson, Vickie Wayne, Lynda Doomy, Michele Wall, Valerie Bitterman, Cindi Young, Rachel Grice, Lioubov Poliakova, Jorge Davalos, David Rosenbaum, Mark Boulware, Heather Mazzola, J. Russell Strader, Russell Linsky, David Schwartz, Elizabeth Graf, Alicia Gneiting, Melissa Palmblad, Ashley Donlin, Emily Ensminger, Hillary Garcia, Dawn Robinson, Carolyn Tran, Jeffrey Jacqmein, Darlene Bartilucci, Michael Koren, Barbara Maluchnik, Melissa Parks, Jennifer Miller, Cynthia DeFosse, Albert B. Knouse, Amy Delancey, Stephanie Chin, Thomas Stephens, Mag Sohal, Juana Ingram, Swarooparani Kumar, Heather Foley, Nina Smith, Vera McKinney, Linda Schwarz, Judith Moore, Hildreth Vernon Anderson, Stefano Sdringola-Maranga, Ali Denktas, Elizabeth Turrentine, Rhonda Patterson, John Marshall, Terri Tolar, Donna Patrick, Pamela Schwartzkopf, Anthony M. Fletcher, Frances R. Harris, Sherry Clements, Tiffany Brown, William Smith, Stacey J. Baehl, Robin Fluty, Daniel VanHamersveld, Dennis Breen, Nancy Bender, Beverly Stafford, Tamika Washington, Margaret N. Pike, Mark A. Stich, Evyan Jawad, Amin Nadeem, Jill Nyland, Rhonda Hamer, Kendra Calhoun, Charlotte Mall, Samuel Cadogan, Kati Raynes, Richard Katz, Lorraine Marshall, Rashida Abbas, Jay L. Dinerman, John T. Hartley, Beth Lamb, Lisa Eskridge, Donna Raymond, Kristy Clemmer, Denise M. Fine, Paula Beardsley, Janet Werner, Bette Mahan, Courtney VanTol, Robert Herman, Christine Raiser-Vignola, Felicia McShan, Stefanie A. Neill, David R. Blick, Michael J. Liston, Denetta K. Nelson, Sandra K. Dorrell, Patricia Wyman, Ambereen Quraishi, Fernando Ferro, Frank Morris, Vicki J. Coombs, Autumn M. Mains, Austin A. Campbell, Jeanne Phelps, Cheryl A. Geary, Ellen G. Sheridan, Jean M. Downing, Arie Swatkowski, Tish Redden, Brian Dragutsky, Susan Thomas, Candace Mitchell, Diana Barker, Elanie Turcotte, Deborah Segerson, Jill Guy, Karena De La Mora, Jennifer Hong, Dennis Do, Rose Norris, Faisal Khan, Hector Montero, Stacy Kelly-White, Alan Cleland, Rosalyn Alcalde-Crawford, Melissa Morgan, Brijmohan Sarabu, Megan Minor, Shweta Kamat, Stephanie M. Estes, Nancee Harless, Alicia Disney, Jodi L. Pagano, Chad M. Alford, Noel W. Bedwell, Warren D. Hardy, Kevin DeAndrade, Jessica G. Elmore, Eric Auerbach, Anthony W. Haney, Miriam H. Brooks, Jose Torres, Lois Roper, Terry Backer, Katie Backer, John G. Evans, Ricardo A. Silva, Lorraine H. Dajani, Veronica Yousif, Tammy Ross, Sion K. Roy, Ronald Oudiz, Sajad Hamal, Ferdinand Flores, Amor Leahy, Debra Ayer, Swapna George, Chrisi Carine Stewart, Elvira Orellana, Cristina Boccalandro, Mary Rangel, Suzanne Hennings, Carl Vanselow, Teri Victor, Darlene Birdwell, Paul Haas, Anthony Sandoval, Gina Ciavarella, Caroline Saglam, Amy Bird, Keith Beck, Brian Poliquin, David Dominguez, Brittany Tenorio, Harvonya Perkins, Esther San Roman, Paris Bransford, Christy Lowrance, Marcy Broussard, Mary Ellis, Bobbi Skiles, Jessica Hamilton, Kathryn Hall, Diego Olvera, Julee A. Hartwell, Nevien Sorial, Mary Rickman, Kevin Berman, Nirav Mehta, Annie Laborin, Rodger Rothenberger, Sarah Beauvilliers, Kathy Morrell, Michael P. Schachter, Cindy L. Perkins, Elizabeth A. Gordon, Jennifer Lauer, Kim Bichsel, Kelly Oliver, Leslie J. Mellor, Candice Demattia, Jennifer Schomburg, Yenniffer Moreno, Eduardo Mansur-Garza, Lena Rippstein, Lorie Chacon, Andrea Pena, Michelle King, Susan Richardson, Annette Jessop, Nicole Tucker, Whitney Royer, Gilbert Templeton, Ann Moell, Christine Weller, Melissa J. Botts, Gretel Hollon, Elsa Homberg-Pinassi, Paula Forest, Aref Bin Abhulhak, Devona Chun-Furlong, Deborah Harrington, Emily Harlynn, Marjorie Schmitt, Constance Shelsky, Patricia Feldick, Mary Cherrico, Courtney Jagle, Nicholas Warnecke, Debra Myer, Deanna J. Ruder, Albina Underwood, Alan Rauba, George Carr, Barbara Oberhaus, Jessica Vanderfeltz, Mary Jo Stucky-Heil, Dale R. Gibson, Vonnie Fuentes, Kimberly L. Talbot, William C. Simon, Katlyn J. Grimes, Christina R. Wheeler, Cassaundra Shultz, Rhonda A. Metcalf, Jennifer L. Hill, Michelle R. Oliver, Basharat Ahmad, Fouzal Azeem, Abdul Rahim, George H. Freeman, Dawn Bloch, Heather Freeman, Jamie Brown, Sarah Rosbach, Pamela Melander, Nick Taralson, Alex Liu, Katlyn Harms, Mahfouz Michale, Jose Lopez, Maria Revoredo, Shari Edevane, Sarah Shawley, Timothy L. Jackson, Michael J. Oliver, Dina DeSalle, Patricia J. Matlock, Ionna M. Beraun, Heather Hendrix, Garrett Bromley, Ashley Niemerski, Gabby Teran, Sonia Guerrero, Murtaza Marvi, Zehra Palanpurwala, Andrea Torres, Patty Gloyd, Michelle Conger, Aziz Laurent, Olia Nayor, Catalina S. Villanueva, Munira Khambati, Tabetha J. Mumford, Melanie J. Castillo, Taddese Desta, Jerome Robinson, La Shawn Woods, Anita Bahri, Nancy Herrera, Cecilia Casaclang, Jeffrey R. Unger, Geraldine Martinez, Mia K. Moon, Stephen M. Mohaupt, Larry Sandoval, Louisito Valenzuela, Victora Ramirez, Nelly Mata, Veronica Avila, Marisol Patino, Cynthia Montano-Pereira, Omar Barnett, William M. Webster, Lorraine M. Christensen, Leighna Bofman, Melanie Livingston, Stacey Adams, Joseph Hobbs, Leesa Koskela, Mia Katz, Samuel Mujica-Trenche, Franklin Cala, Noreen T. Rana, Jennifer Scarlett, Milagros Cala Anaya, Marsha R. Jones, Kelly D. Hollis, Debbie Roth, Kristin Eads, Tina Watts, Judy Perkins, Alice Arnold, Daniel C. Ginsberg, Denise Quinn, Nicole Cureton, David B. Fittingoff, Mohammed I. Iqbal, Stephen R. White, Edith Sisneros, Michelle Ducca, David Streja, Danny Campos, Jennifer L. Boak, Farzeen Amir, Felice Anderson, James J. Kmetzo, Mary O. Bongarzone, Dawn Scott, Mary Grace De Leon, Cynthia Buda, William Graettinger, Michelle Alex, Erika Hess, James Govoni, Melissa Bartel, Travis L. Monchamp, Julie S. Roach, Sara Gibson, Amy M. Allfrey, Kristen Timpy, Kathy Bott, Karin A. Soucy, Jean Willis, Cecilia A. Valerio, Anusha Chunduri, Rebecca Coker, Nicole Vidrine, Ellen A. Thompson, Mark A. Studeny, Melissa K. Marcum, Tammy S. Monway, Douglas L. Kosmicki, Melissa J. Kelley, Corey M. Godfrey, Susan L. Krenk, Randy R. Holcomb, Deb K. Baehr, Mary K. Trauernicht, David Rowland Lowry, Betty Bondy Herts, Jeanne E Phelps, Jean-Marie Downing, Carol Gamer Dignon, Elisabeth S. Cockrill, Pravinchandra G. Chapla, Diane Fera, Margaret Chang, Patricia Fredette, Tamie Ashby, Renee Bergin, Zebediah A. Stearns, David B. Ware, Rachael M. Boudreaux, Joanna Rodriguez, Robert McKenzie, Amanda Huber, Rebecca Sommers, Heather Rowe, Stacy McLallen, Michale Haynes, Ashley Adamson, Janice Henderson, Lori McClure, Beverly A. Harris, Laura Ference, Sue Meissner-Dengler, Lisa Treasure, Doreen Nicely, Timothy L. Light, Tracey A. Osborn, Kimberly J. Mai, Pablo Vivas, Jose Rios, Dunia Rodriguez, Roger DeRaad, James Walder, Oscar Bailon, Denice Hockett, Debbie Anderson, Kelli McIntosh, Amber Odegard, Andrew Shepherd, Mary Seifert, Laurence Kelley, Rajendra Shetty, Michael Castine, David Brill, Gregory Fisher, Nicole Richmond, Kathleen Gray, Patricia Miller, Charlene Coneys, Yarixa Chanza, Monica Sumoza, Victoria M. Caudill, Kelly D. Harris, Courtney A. Manion, Melody J. Lineberger-Moore, Julie J. Wolfe, Barbara J. Rosen, Patricia DiVito, Janet L. Moffat, Christina Michaelis, Prashant Koshy, Diana Perea, Ghaith Al Yacoub, Stephanie Sadeghi, Thomas D. LeGalley, Rudolph F. Evonich, William J. Jean, Gary M. Friesen, John M. Pap, David A. Pesola, Mark D. Cowan, Kristofer M. Dosh, Dianna Larson, Adele M. Price, Jodi A. Nease, Jane E. Anderson, Lori A. Piggott, Robert Iwaoka, Kevin Sharkey, Edward McMillan, Laurie Lowder, Latisha Morgan, Kyle Davis, Tara Caldwell, Erica Breglio, Jasmine Summers, Rachel Poulimas, Muhammad Zahid, Hamid Syed, Maria Escobar, Jacob Levy, Rahma Warsi, Carol Ma, Puxiao Cen, Kimberly A. Cawthon, Delores B. Barnes, Deanna G. Allen, Margaret L. Warrington, Carol R. Stastny, Robin J. Michaels, Mohamad Saleh, John Sorin, Sunny Rathod, Urakay Juett, Steven Spencer, Aziza Keval, Jill McBride, Shane Young, Catherine Baxter, Carol Rasmussen, Shari L. Coxe, Luis Campos, Shahin Tavackoli, Diana Beckham, Darlynee Sanchez, Karanjit Basrai, Dorian Helms, Erica Clinton, Kasie Smith, Henry Cusnir, Mary Klaus Clark, Madhavagopal V. Cherukuri, Ameta Scarfaru, Stephen D. Nash, Loretta C. Grimm, Anna Grace, Kylie McElheran, Dino Subasic, Zedrick Buhay, Janet Litvinoff, Deepak Shah, Shannon Cervantes, Freda Usher, Farra Yasser, Theodore Trusevich, Ronnie L. Garcia, Jamison Wyatt, Rahul Bose, Holllilyn Miska, Traci Spivey, Amy B. Wren, Katie E. Vance, Lani L. Holman, Pam Gibbons, Elaine Eby, Sandra Shepard, Soratree Charoenthongtrakul, Brett Snodgrass, Mohammed Nazem, Shelly Keteenburg, Prathima Murthy, Frederic Prater, Ashley Rumfelt, Christina Eizensmits, Lisa Iannuzzi, Pourus R. Patel, Clellia Bergamino, Elizabeth McFeaters, Botros Rizk, Emiljia Pflaum, Danny Kalish, Rex Ambatali, Mona Ameli, Delaina Sanguinetti, Rakesh Vaidya, Martinus A.W. Broeders, Dorman Henrikus, Adrianus F.M. Kuijper, Nadea Al-Windy, Michael Magro, Karim Hamraoui, Ismail Aksoy, Guy L.J. Vermeiren, H.W.O. Roeters van Lennep, Gerard Hoedemaker, Johannes Jacobus Remmen, Kjell Bogaard, Dirk van der Heijden, Nicole MJ Knufman, Joost Frederiks, Johannes Willem Louwerenburg, Piet van Rossum, Johannes Milhous, Peter van der Meer, Arno van der Weerdt, Rob Breedveld, Mitran Keijzers, Walter Hermans, Ruud van de Wal, Peter A.G. Zwart, Marc M.J.M. van der Linden, Gerardus Zwiers, Dirk J. Boswijk, Jan Geert Tans, Jacob van Eck, Maarten V. Hessen, Barnabas J.B. Hamer, Stieneke Zoet-Nugteren, Lucien Theunissen, E.A. van Beek, Remco Nijmeijer, Pieter R. Nierop, Gerard Linssen, H.P. Swart, Timo Lenderink, Gerard L. Bartels, Frank den Hartog, Brian J. Berg van den, Wouter van Kempen, Susanne Kentgens, Gloria M. Rojas Lingan, Martinus M. Peeters, Hilligje Keterberg, Melchior Nierman, Annemieke K. den Hollander, Jacqueline Hoogendijk, Christine Voors-Pette, Vicdan Kose, Peter Viergever, Larysa Yena, Viktor Syvolap, Mykola P. Kopytsya, Olga Barna, Svitlana S. Panina, Mykhailo I. Lutai, Oxana V. Shershnyova, Iryna Luzkiv, Larysa S. Bula, Sergii Zotov, Ivan Vyjhovaniuk, Olena Lysunets, Volodymyr I. Koshlia, Nataliya Sydor, Myroslava F. Vayda, Olexiy Ushakov, Mykola Rishko, Viktor P. Shcherbak, Yevgeniya Svyshchenko, Vira Tseluyko, Andriy Yagensky, Viktoriia I. Zolotaikina, Olga Godlevska, Larysa Ivanova, Olena Koval, Olena I. Mitchenko, Galyna Y. Kardash, Yurii S. Rudyk, Mykola Stanislavchuk, Volodymyr Ivanovych Volkov, Olena G. Karlinskaya, Susanna A. Tykhonova, Nikolay Vatutin, Ganna Smirnova, Volodymyr M. Kovalenko, Viktor Lizogub, Denys Sebov, Oleksandr Dyadyk, Svetlana Andrievskaya, Mykola P. Krasko, Alexander N. Parkhomenko, Lidiya Horbach, Iryna G. Kupnovytska, Tetyana Pertseva, Oleksandr Karpenko, Dmytro Reshotko, Svitlana V. Zhurba, Leonid Rudenko, Viktoriia Yu Zharinova, Valerii B. Shatylo, Yuriy I. Karpenko, Mariya A. Orynchak, Tatiana R. Kameneva, Elena Zherlitsina, Diana N. Alpenidze, Grigoriy P. Arutyunov, Elena Baranova, Boris Bart, Dmitriy I. Belenkiy, Svetlana A. Boldueva, Elena A. Demchenko, Vera V. Eltishcheva, Alexander M. Gofman, Boris M. Goloshchekin, Ivan Gennadyevich Gordeev, Nikolay Gratsianskiy, Gadel Kamalov, Niyaz R. Khasanov, Irina M. Kholina, Zhanna D. Kobalava, Elena V. Kobeleva, Alexandra O. Konradi, Victor A. Kostenko, Andrey Dmitrievich Kuimov, Polina Y. Ermakova, Sofia K. Malyutina, Alexey V. Panov, Natalia V. Polezhaeva, Olga Reshetko, Nataliya P. Shilkina, Sergey B. Shustov, Elena A. Smolyarchuk, Raisa I. Stryuk, Elena Yurievnar Solovieva, Andrey V. Susekov, Natalia Vezikova, Svetlana N. Ivanova, Alexander A. Petrov, Vladimir O. Konstantinov, Alina S. Agafina, Victor Gurevich, Konstantin N. Zrazhevskiy, Tatiana V. Supryadkina, Nikita B. Perepech, Vadim L. Arkhipovskiy, Dmitry Yu Butko, Irina A. Zobenko, Olga V. Orlikova, Viktor Mordovin, Olga L. Barbarash, Anastasiya Lebedeva, Vladimir Nosov, Oleg V. Averkov, Elena P. Pavlikova, Yuri B. Karpov, Marina Lvovna Giorgadze, Oleg A. Khrustalev, Mikhail Arkhipov, Tatiana A. Raskina, Julia V. Shilko, Yulia Samoilova, Elena D. Kosmacheva, Sergey V. Nedogoda, Kathleen Coetzee, Lesley J. Burgess, F.C.R. Theron, Iftikhar O. Ebrahim, Gerbrand A. Haasbroek, Maria Pretorius, Julien S. Trokis, Dorothea V. Urbach, Mark J. Abelson, Adrian R. Horak, Aysha E. Badat, Ellen M. Makotoko, Hendrik Du Toit Theron, Padaruth Ramlachan, Clive H. Corbett, Ismail H. Mitha, Hendrik F.M. Nortje, Dirkie J. Jansen van Rensburg, Peter J. Sebastian, F.C.J. Bester, Louis J. van Zyl, Brian L. Rayner, Elżbieta Błach, Magda Dąbrowska, Grzegorz Kania, Agata E. Kelm-Warchol, Leszek P. Kinasz, Janusz Korecki, Mariusz Kruk, Ewa Laskowska-Derlaga, Andrzej Madej, Krzysztof Saminski, Katarzyna Wasilewska, Katarzyna Szymkowiak, Małgorzata Wojciechowska, Natalia Piorowska, Andrzej Dyczek, Rajpal K. Abhaichand, Ramesh B. Byrapaneni, Basavanagowdappa Hattur, Malipeddi Bhaskara Rao, Nitin Ghaisas, Sujit Shankar Kadam, Jugal B. Gupta, Santhosh M. Jayadev, V.A. Kothiwale, Atul Mathur, Vijay Bhaskar, Ravi K. Aluri, Udaya P. Ponangi, Mukesh K. Sarna, Sunil Sathe, Manish K. Sharma, Jilendra Pal Singh Sawhney, Chakrabhavi B. Keshavamurthy, Arun Srinivas, Hemant P. Thacker, A. Sharda, Johny Joseph, Sunil Dwivedi, Viswanathan Mohan, Rajendra K. Premchand, Jacques Bedard, Jean Bergeron, Ronald Collette, David Crowley, Richard Dumas, Sam Henein, Geoff Moran, William F. O’Mahony, Michael O’Mahony, Sammy Chan, Mark H. Sherman, Graham C. Wong, Brian D. Carlson, Milan K. Gupta, David Borts, Sean R. Peterson, Martyn Chilvers, Allan J. Kelly, Jean C. Gregoire, Simon Kouz, Josep Rodés Cabau, Minodora Andor, Mircea Cinteza, Radu Ciudin, Radu I. Cojan, Roxana O. Darabont, Dan-Lucian Dumitrascu, Carmen Fierbinteanu-Braticievici, Ana Gabriela Fruntelata, Constantin Militaru, Bogdon E. Minescu, Doina Luminita Serban, Florin Mitu, Dorel Nastase Melicovici, Ovidiu Petrascu, Octavian M. Pirvu, Cristian Podoleanu, Calin Pop, Rodica-Valentina V. Stanescu-Cioranu, Adrian Tase, Cristina Voiculet, Constantine N. Aroney, Anthony M. Dart, Timothy Davis, Karam Kostner, David N. O’Neal, Peter W. Purnell, Bhuwanendu B. Singh, David R. Sullivan, Peter Thompson, Gerald F. Watts, Adam F. Blenkhorn, John V. Amerena, Rafeeq Samie, Randall Hendriks, Joseph Proietto, Nikolai Petrovsky, Alan Whelan, David Colquhoun, Russell S. Scott, Simon C. Young, Tammy Pegg, Samuel JS Wilson, Andrew W. Hamer, Richard A. Luke, Hamish H. Hart, Gerard P. Devlin, Gerard T. Wilkins, Ian F. Ternouth, Samraj Nandra, Bruno S. Loeprich, Nicole McGrath, Stuart L. Tie, Rob J. Bos, Alexandra Wils, Tamara Jacobs, Erik A. Badings, Lillian A. Ebels-Tuinbeek, Mayke L. Scholten, Esther Bayraktar-Verver, Debby Zweers, Manoek Schiks, Carolien Kalkman, Tineke Tiemes, Jeanette Mulderij, Katarzyna Dabrowska, Wilma Wijnakker, Riny Van de Loo, Jeanne de Graauw, Giny Reijnierse, Mirjam van der Zeijst, Mariska Scholten, Henk R. Hofmeijer, Antoinette van Dijk-van der Zanden, Dineke J. van Belle, Jan Van Es, Gera Van Buchem, Wendy Zijda, Harald Verheij, Linnea Oldenhof-Janssen, Martina Bader, Marije Löwik, Sandra Stuij, Pascal Vantrimpont, Krista van Aken, Karen Hamilton, Han Blömer, Gabriela van Laerhoven, Raymond Tukkie, Maarten Janssen, Gerard Verdel, Jon Funke Küpper, Bob van Vlies, Caroline Kalkman, Joke Vooges, Marinella Vermaas, Rachel Langenberg, Niek Haenen, Frans Smeets, Arko Scheepmaker, Marcel Grosfeld, Ilvy Van Lieshout, Marleen van den Berg, Marian Wittekoek, Petra Mol, Antionette Stapel, Margaretha Sierevogel, Nancy van der Ven, Annemiek Berkelmans, Eric Viergever, Hanneke Kramer, Wilma Engelen, Karen V. Houwelingen, Thierry X. Wildbergh, Arend Mosterd, Coriet Hobé-Rap, Marjan van Doorn, Petra Bunschoten, Michel Freericks, Mireille Emans, Petra Den Boer-Penning, Els Verlek, Christine Freericks, Cornelis de Nooijer, Christina Welten, Ingrid Groenenberg, Claudia van der Horst, Esther Vonk, Geert Tjeerdsma, Gerard M. Jochemsen, Corinne van Daalen, Ingrid Y. Danse, Lucy Kuipers, Anke Pieterse, Antonius Oomen, Daan de Waard, Willem Jan Flu, Zusan Kromhout, Petra Van der Bij, Rob Feld, Brigitta Hessels-Linnemeijer, Rob Lardinois, Jan L. Posma, Zwanette R. Aukema-Wouda, Marjolijn Hendriks-van Woerden, Desiree van Wijk, Driek P. Beelen, Ingrid H. Hendriks, Jan J. Jonker, Stefanie Schipperen, Vicdan Köse, Gloria Rojas, Linda Goedhart, Hanneke van Meurs, Jacqueline Rijssemus, Lindy Swinkels-Diepenmaat, Marloes de Louw-Jansen, Dominique Bierens-Peters, Willem W. van Kempen, Marianne E. Wittekoek, Irmaina Agous, Geert Schenk, Janneke Wittekoek, Kevin Cox, Deborah F. Julia, Jan J.C. Jonker, Roel Janssen, Melchor Nierman, Hilligje Katerberg, Irene van der Haar, Willem W. Van Kempen, Taco van Mesdag, Leyda M. Alvarez Costa, Manon Schensema, Salomé Zweekhorst, Deborah Font Julia, Lauri Hanewinckel, Joyce Olsthoorn, Johan C. Berends, Arie C. van der Spek, Roy van der Berg, Rob J. Timmermann, Ingrid Boerema, Iryna Mudruk, Anna Khrystoforova, Serhii Kyselov, Yaroslava V. Hilova, Pavlo Logoida, Nataliia A. Sanina, Ilona P. Golikova, Olena O. Nemchyna, Ivan I. Isaichikov, Olga B. Potapova, Iurii V. Gura, Larysa Berestetska, Olena O. Kulianda, Oleksandr Tantsura, Oleksandr S. Kulbachuk, Volodymyr Petsentiy, Ihor Biskub, Tetyana Handych, Oleg Lagkuti, Alyna Gagarina, Taras Chendey, Oksana F. Bilonko, Olena Matova, Larysa Bezrodna, Olena Yarynkina, Tetiana Ovdiienko, Volodymyr Randchenko, Maryna Mospan, Olena Butko, Olga Romanenko, Mykhailo Pavelko, Iryna Sichkaruk, Svitlana O. Lazareva, Olena A. Kudryk, Inessa M. Koltsun, Tetiana Magdalits, Sergei Zadorozhniy, Kira Kompaniiets, Andrii Ivanov, Sergiy Romanenko, Pavlo Kaplan, Vadym Y. Romanov, Oksana P. Mykytyuk, Nataliia S. Zaitseva, Sergiy N. Pyvovar, Lyudmyla Burdeuna, Emerita Serdobinska, Tatiana I. Shevchenko, Igor I. Ivanytskyi, Olena V. Khyzhnyak, Nataliya Kalinkina, Olena Keting, Olena Sklyanna, Olga Kashanska, Anna Shevelok, Marina Khristichenko, Ievgenii Y. Titov, Danilenko O. Oleksander, Nataliia S. Polenova, Nataliia Altunina, Viktoriia Kororaieva, Stanislav Zborovskiy, Leonid Kholopov, Iurii Suliman, Lanna Lukashenko, Stanislav Shvaykin, Olexandr M. Glavatskiy, Roman O. Sychov, Roman L. Kulynych, Oleksandr A. Skarzhevskyi, Nataliia V. Dovgan, Marta Horbach, Olga Cherkasova, Iryna Tyshchenko, Liudmyla Todoriuk, Svitlana Kizim, Nataliia Brodi, Oleksandr Ivanko, Olga Garbarchuk, Liudmyla Alieksieieva, Tetiana L. Shandra, Olena Beregova, Larisa An Bodretska, Svitlana S. Naskalova, Ivanna A. Antoniuk-Shcheglova, Olena V. Bondarenko, Natalia G. Andreeva, Iryna I. Vakalyuk, Olha S. Chovganyuk, Nataliya R. Artemenko, Kiril A. Maltsev, Natalia Kalishevich, Natalia G. Kondratyeva, Svetlana A. Nikitina, Maria V. Martjanova, Anna V. Sokolova, Dmitrii O. Dragunov, Olga Kolesnik, Vera Larina, Oxana V. Tsygankova, Maria Ivanova, Illia A. Karpov, Elena M. Aronova, Ekaterina S. Vedernikova, Ekaterina I. Lubinskaya, Taras Y. Burak, Sergey I. Skichko, Farhad Rasulev, Ekaterina B. Soldatova, Alexander L. Fenin, Ilya I. Laptev, Elena E. Luchinkina, Alexandr Akatov, Natalia V. Polenova, Natalia N. Slavina, Irina N. Korovnika, Marina Yu Prochorova, Regina Shakirova, Elena N. Andreicheva, Olga A. Krasnova, Tinatin V. Lobzhanidze, Tatiana B. Dmitrova, Viktoriya V. Stakhiv, Maria I. Pechatnikova, Alexandra V. Panova, Maria Y. Tipikina, Oxana P. Rotar, Nikolay A. Bokovin, Saule K. Karabalieva, Farid Y. Tumarov, Elena V. Vasileva, Natalya Gennadevna Lozhkina, Ekaterina V. Filippova, Alisa I. Sharkaeva, Ekanerina V. Filippova Deilik, Natalia Yu Tolkacheva, Elena N. Domracheva, Andrey N. Ryabikov, Inga T. Abesadze, Marianna Z. Alugishvili, Elena P. Nikolaeva, Nadezda V. Smirnova, Valentina I. Rodionova, Polina V. Dolovstaya, Igor E. Yunonin, Sergey V. Kadin, Tatyana S. Sveklina, Anna V. Bushmanova, Elena L. Barkova, Irina S. Gomova, Yana V. Brytkova, Tatiana B. Ivanova, Marina Y. Zubareva, Inga Skopets, Lybov A. Galashevskaya, Emilia D. Butinskaya, Olga G. Gusarova, Natalia B. Kalishevich, Yana R. Pavlova, Marianna P Serebrenitskaya, Vitalina F. Grygorieva, Gulnara R. Kuchaeva, Inna A. Vasileva, Gulnara I. Ospanova, Yulia V. Vahrusheva, Irina A. Semenova, Irina E.E. Mikhailova, Olga O. Kvasova, Valeria D. Shurygina, Alexey E. Rivin, Alexey O. Savelyev, Alexey A. Savelyev, Olesya O. Milyaeva, Nadezhda N. Lapshina, Ninel A. Lantsova, Pavel V. Alexandrov, Evgeniy A. Orlikov, Alla Falkovskaya, Tatiana Ripp, Sergei Triss, Stanislav Pekarskiy, Sitkova Ekaterina, Evgeniya N. Zhuravleva, Olga Perova, Galina Kovaleva, Liubov Koroleva, Lydia Mishchenko, Boris P. Garshin, Svetlana A. Kutuzova, Lyudmila I. Provotorova, Igor P. Zadvorny, Olga V. Okhapkina, Anatoly O. Khrustalev, Tatiana Suvorova, Elena S. Shaf, Varvara A. Vershinina, Andrey A. Kozulin, Oxana A. Oleynik, Irina Y. Martynova, Natalia V. Kizhvatova, Alla S. Salasyuk, Vera V. Tsoma, Alla A. Ledyaeva, Elena V. Chumachek, S.C. Blignaut, Tersia Y. Alexander, Chano Du Plessis, Thirumani Govender, Samatha M. Du Toit, Leya Motala, Areesh Gassiep, Christina Naude (Smit), Marli Terblanche, Marlien Snoer (Kruger), Berenice Pillay, De Vries Basson, Marisa E. Theron, Bianca Fouche, Mareli E. Coetzee, Pieter Odendall, Frederik H. Van Wijk, Anna-Mari Conradie, Trudie Van der Westhuizen, Carine Tredoux, Mohamed S. Mookdam, Andie J. Van der Merwe, Karin Snyman, Gerda Smal, Yvonne De Jager, Thomas A. Mabin, Annusca King, Lindy L. Henley, Brenda M. Zwane, Jane Robinson, Marinda Karsten, Andonia M. Page, Valerie Nsabiyumva, Charmaine Krahenbuhl, Jaiprakash D. Patel, Yunus E. Motala, Ayesha Dawood, Nondumiso B. Koza, Lenore M.S. Peters, Shavashni Ramlachan, Wilhelm J. Bodenstein, Pierre Roux, Lizelle Fouche, Cecilia M. Boshoff, Haroon M. Mitha, Fathima Khan, Henry P. Cyster, Helen Cyster, E. C. Wessels, Florence J. Jacobs, Melanie A. Sebastian, Deborah A. Sebastian, Nadia Mahomed, Ignatius P. Immink, Celia Cotzee, Tanja Cronje, Madele Roscher, Maria Le Roux, Yvonne A. Trinder, Renata Wnętrzak-Michalska, Magdalena Piszczek, Andrzej Piela, Ewa Czernecka, Dorota Knychas, Alina Walczak, Izabella Gładysz, Katarzyna Filas, Ewelina Kiluk, Krzysztof Świgło, Iwona Jędrzejczyk, Kamila Łuczyńska, Katarzyna Tymendorf, Wojciech Piesiewicz, Wojciech L. Kinasz, Stefan Samborski, Ilona Bartuś, Gramzyna Latocha Korecka, Ewa Gulaj, Jolanta Sopa, Bogusław Derlaga, Marcin Baisiak, Allicia Kowalisko, Edyta Stainszewska-Marasazlek, Bartosz Szafran, Malgorzata Swiatkiewicz, Artur Racewicz, Sławomir Grycel, Jerzy Supronik, Sylwia Walendziuk, Magdalena Tarantowicz, Agata Stasiak, Anna Sidorowicz-Białynicka, Marek Dwojak, Ewa Jaźwińska-Tarnawska, Katarzyna Kupczyk, Kamila Martowska, Kamila Kulon, Katarzyna Gajda, Bivin Wilson, Krithika Velusamy, Swaidha S. Sadhiq, Bhavani Siddeshi, M. Bhanukumar, Abhishek Srivatsav, Madhan Ramesh, Sri Harsha Chalasani, Mini Johnson, Prashanth Gopu, Jeesa George, Sowmya Reddy, Swetha Tessy Thara Eleena, Damodara Rao Kodem, Haritha N. Nakkella, Padma Kumari Mandula, Anjan Kumar Vuriya, Syamala Rajana, Aruna Kale, Tiwari Rajeev, Raina Jain, Vipin Jain, Srilakshmi Mandayam Adhyapak, Lumin Sheeba, Uma C R, Ramya R, Aditya V. Kulkarni, M.S. Ganachari, Ruma Sambrekar, Mohammad Bilal, Kalyan Chakravarthy, Ravi Badhavath, Sravan Kumar, Meenakshi Simhadri, Farooque Salamuddin, Venkat Prasad, Vivek Dwivedi, Sudha Sarna, Tilak Arora, Deepak Chawla, Archana Sathe, Chaware Gayatree, Ajeet Nanda, Ram Avtar, Jyoti Sharma, Vaibhavi P S, Sasirekha D, Deepthi Kobbajji, Ramya Ningappa, Shwetha Shree, Chandrashekar K, Nandini M R, Sowjanya S, Devika I G, Yashaswini N, Sonika G, Rathna L, Priyanka R, Rupal J. Shrimanker, Lakshmi Vinutha Reddy, K. Sumathi, Babitha Devi, Bina N. Naik, Rohini Manjunath, Rajeshwari Ashok, Tony V. Kunjumon, Jesline Thomas, Shaik Samdhani, Kasthuri Selvam, Poongothai Subramani, Nandakumar Parthasarathy, Nirmal K. Bohra, Anvesh K. Gatla, Cheryl Horbatuk, Julie Sills, E B. Davey, Liz Paramonczyk, Olga Racanelli, Sandy Strybosch, Andre Belanger, Jean Palardy, Alicia Schiffrin, Sylvie Gauthier, Norman Kalyniuk, Shawn D. Whatley, Heather Lappala, Grishma Patel, Matthew Reeve, Catherine Moran, Jody Everitt, Teresa Ferrari, Christine Bouffard, Jirir Frohlich, Gordon Francis, John Mancini, Gregory Bondy, Debbie DeAngelis, Patricia Fulton, David W. Blank, Angela Lombardo, Mylène Roy, Jackie Chow, Hyman Fox, William J. Grootendorst, Angela Hutchinson, Sharon M. Chan, Christie Fitzgerald, Lynn Wilkins, Rebecca L. Raymond, Arlene Reyes, Lavoie Marc André, Denis Fortin, Hélène Ouimet, Thanh-Thao Tôn-Nu, Martine Dussureault, Marie-Hélène Blain, Madeleine Roy, Nathalie Kopajko, Chantal Fleury, Karine Maheux, Gabriela Valentina Ciobotaru, Maria C. Constantinescu, Carmen-Lucia Gherghinescu, Ana-Maria Avram, Ioan Manitiu, Aura Sinpetrean, Lucian Pop, Delia Lupu, Radu Usvat, Ana Petrisor, Nicoleta Dumitru, Camelia Moruju, Adelina Gheorghita, Magda V. Mitu, Cosmin Macarie, Ana Maria Pop, Maria-Catalina Diaconu, Iulia Grancea, Mihaela Cosma, Mihaela Crisan, Elizabeth Herron, Paul Nestel, Sally B. Kay, Kaye S. Carter, Imran Badshah, Ashley Makepeace, Jocelyn Drinkwater, Michelle England, Azette Rafei, Kylie Patterson, Alicia Jenkins, Sybil McAuley, Sue M. Kent, Joy E. Vibert, Leonie Perrett, Thomas David, Samantha L. Kaye, Monika O’Connor, Nimalie J. Perera, Nicole T. Lai, Kerry A. Kearins, Christinia Dicamillo, Heather Anderson, Louise Ferguson, Sharon D. Radtke, Charles T. Thamarappillil, Janice M. Boys, Anita K. Long, Toni Shanahan, Michael Nyguyen, Nicole Forrest, Gill Tulloch, Della Greenwell, Sarah L. Price, Aye N. Tint, Priya K. Sumithran, Tamara L. Debreceni, Lisa Walker, Mary Caruana, Kira Edwards, Maria Stathopoulos, Cilla Haywood, Dimitar Sajkov, Sharen Pringle, Anne Tabner, Kathrina Bartolay, Chamindi Abeyratne, Kylie Bragg, Patrick Mulhern, Peter Purnell, Lyn Williams, Jane Hamlyn, Aurelia Connelly, Jan Hoffman, Samantha Bailey, Jane Kerr, Zarnia Morrison, Sarah Maeder, Roberta McEwan, Prasanna Kunasekera, Patrice McGregor, Jo Young, Sharon Berry, Rick Cutfield, Michelle Choe, Catherine McNamara, Narrinder K. Shergill, Petra Crone, Miles G. Williams, Keith Dyson, Diana H. Schmid, Audrey C. Doak, Melissa Spooner, Colin Edwards, Anne Turner, Grainne M. McAnnalley, Raewyn A. Fisher, Fraser B. Hamilton, Denis H. Friedlander, Melissa R. Kirk, Jayne E. Scales, Marguerite A. McLelland, Neelam A. Dalman, Cathy E. Vickers, Carolyn Jackson, Wendy Coleman, Phillip I. Garden, and Wendy F. Arnold

Subjects
Male, medicine.medical_specialty, Rate ratio, Double-Blind Method, Ischemia, Risk Factors, Physiology (medical), Internal medicine, medicine, Clinical endpoint, Humans, Myocardial infarction, Coronary Artery Bypass, Stroke, Aged, business.industry, Unstable angina, Hazard ratio, Absolute risk reduction, Middle Aged, medicine.disease, Eicosapentaenoic Acid, Number needed to treat, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Published
2021

20. Analgesic use in adolescents with patellofemoral pain or Osgood–Schlatter Disease: a secondary cross-sectional analysis of 323 subjects

Author

Ewa M. Roos, Jens Lykkegaard Olesen, Michael Skovdal Rathleff, Per Hölmich, Alessandro Andreucci, Sten Rasmussen, and Kristian Thorborg

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Cross-sectional study, Analgesic, Population, cross-sectional studies, Pain, Disease, Knee Joint, Logistic regression, knee joint, Young Adult, medicine, Humans, Osteochondrosis, Child, education, Analgesics, education.field_of_study, business.industry, medicine.disease, Cross-Sectional Studies, Anesthesiology and Pain Medicine, Knee pain, pain management, Patellofemoral Pain Syndrome, analgesics, Physical therapy, Female, Neurology (clinical), medicine.symptom, patellofemoral pain syndrome, business, Patellofemoral pain syndrome
Abstract

Objectives The prevalence of pain medication use for adolescent knee pain and factors associated with use are not well understood. This study aimed to determine the self-reported use of pain medication for knee pain and identify factors associated with use in adolescents (age 10–19) with longstanding knee symptoms. Methods In this exploratory cross-sectional study, we performed a secondary analysis of data previously collected in 323 adolescents with longstanding knee pain. Factors associated with pain medication use were assessed using multivariable logistic regressions. Analyses were repeated with stratification by age, sex, sport participation frequency, knee pain duration, and knee pain intensity. Results Among 323 adolescents (mean age 14.4 ± 2.5, 73% female), 84% had patellofemoral pain, (peri- or retro-patellar pain during loaded bending of the knee) and 16% had Osgood–Schlatter Disease (apophysitis with swelling and localized pain at the tibial tuberosity). Twenty-one percent (95% CI 16–25%) of adolescents reported pain medication use for their knee pain, with no difference in usage between those ≤ vs. > 15 years of age (21%, 95% CI 16–27% vs. 20%, 95% CI 13–29%). Adolescents with patellofemoral pain reported greater usage than their counterparts with Osgood–Schlatter Disease (22%, 95% CI 17–28% vs. 12%, 95% CI 4.5–24.3%). The most consistent factor associated with use was knee-related symptoms, observed in both the overall (OR 0.97, 95% CI 0.94–0.99) and stratified analyses (ORs ranged from 0.89 to 0.96). Conclusions Approximately one in five adolescents with longstanding knee pain reported pain medication use, particularly in adolescents with patellofemoral pain. Knee-related symptoms most consistently associated with the use of pain medications in this population. Future longitudinal studies with data collected at multiple time-points are needed to validate these findings. Implications Self-reported pain medication use is common in adolescents with longstanding knee pain, even though whether pharmacological therapy is the best pain management option at this young age is debatable. Reliance on pain medication at an early age could potentially hamper the development of healthy pain coping strategies and increase the risk of dependence and misuse later in life. Future studies should assess the safety, efficacy, and risks of long-term use of pain medications for adolescent knee pain.

Published
2021

21. Cerebral lactate uptake during exercise is driven by the increased arterial lactate concentration

Author

Nikolai Baastrup Nordsborg, Henrik Toft Sørensen, Thomas Christian Bonne, Niels Jacob Aachmann-Andersen, Morten Zaar, Niels H. Secher, Henning B. Nielsen, Christoph Siebenmann, Peter Vestergaard Rasmussen, and Carsten Lundby

Subjects
Male, Anaerobic, medicine.medical_specialty, Physiology, Adrenergic beta-Antagonists, Propranolol, Blood–brain barrier, Physiology (medical), Internal medicine, Faculty of Science, medicine, Humans, Lactic Acid, Exercise, Lactate concentration, Chemistry, Brain, Metabolism, Bicycling, Perfusion, Endocrinology, medicine.anatomical_structure, Diffusion gradient, medicine.drug
Abstract

Exercise facilitates cerebral lactate uptake, likely by increasing arterial lactate concentration and hence the diffusion gradient across the blood brain barrier. However, non-specific β-adrenergic blockade by propranolol has previously reduced the arterio-jugular venous lactate difference (AVLac) during exercise, suggesting β-adrenergic control of cerebral lactate uptake. Alternatively, we hypothesize that propranolol reduces cerebral lactate uptake by decreasing arterial lactate concentration. To test that hypothesis, we evaluated cerebral lactate uptake taking changes in arterial concentration into account. Nine healthy males performed incremental cycling exercise to exhaustion with and without intravenous propranolol (18.7 ± 1.9 mg). Lactate concentration was determined in arterial and internal jugular venous blood at the end of each workload. To take changes in arterial lactate into account we calculated the fractional extraction (FELac) defined as AVLac divided by the arterial lactate concentration. Arterial lactate concentration was reduced by propranolol at any workload (p-1 during maximal exercise without and with propranolol, respectively. While AVLac and FELac increased during exercise (both P < 0.05), they were both unaffected by propranolol at any workload (P = 0.68 and P = 0.26) or for any given arterial lactate concentration (P = 0.78 and P = 0.22). These findings support that, while propranolol may reduce cerebral lactate uptake, this effect reflects the propranolol-induced reduction in arterial lactate concentration and not inhibition of a β-adrenergic mechanism within the brain. We hence conclude that cerebral lactate uptake during exercise is directly driven by the increasing arterial concentration with work rate.

Published
2021

22. Characteristics of adult patients with chronic intestinal failure due to short bowel syndrome:An international multicenter survey

Author

Loris Pironi, Ezra Steiger, Francisca Joly, Palle B. Jeppesen, Geert Wanten, Anna S. Sasdelli, Cecile Chambrier, Umberto Aimasso, Manpreet S. Mundi, Kinga Szczepanek, Amelia Jukes, Miriam Theilla, Marek Kunecki, Joanne Daniels, Mireille Serlie, Florian Poullenot, Sheldon C. Cooper, Henrik H. Rasmussen, Charlene Compher, David Seguy, Adriana Crivelli, Lidia Santarpia, Francesco W. Guglielmi, Nada Rotovnik Kozjek, Stéphane M. Schneider, Lars Ellegard, Ronan Thibault, Przemysław Matras, Konrad Matysiak, Andrè Van Gossum, Alastair Forbes, Nicola Wyer, Marina Taus, Nuria M. Virgili, Margie O'Callaghan, Brooke Chapman, Emma Osland, Cristina Cuerda, Gábor Udvarhelyi, Lynn Jones, Andre D. Won Lee, Luisa Masconale, Paolo Orlandoni, Corrado Spaggiari, Marta Bueno Díez, Maryana Doitchinova-Simeonova, Aurora E. Serralde-Zúñiga, Gabriel Olveira, Zeljko Krznaric, Laszlo Czako, Gintautas Kekstas, Alejandro Sanz-Paris, Mª Estrella Petrina Jáuregui, Ana Zugasti Murillo, Eszter Schafer, Jann Arends, José P. Suárez-Llanos, Nader N. Youssef, Giorgia Brillanti, Elena Nardi, Simon Lal, Adriana N. Crivelli, Hector Solar Muñiz, Brooke R. Chapman, Ruth Hodgson, Siobhan Wallin, Kay Lasenby, Andre Van Gossum, Andre Dong Won Lee, Henrik Højgaard Rasmussen, Chrisoffer Brandt, Vanessa Boehm, Julie Bataille, Lore Billiauws, Tomas Molnar, Mihaly Zsilak-Urban, Ferenc Izbéki, Peter Sahin, Anna Simona Sasdelli, Merlo F. Dario, Valentino Bertasi, Nunzia Regano, Santarpia Lidia, Lucia Alfonsi, Debora Busni, Lyn Gillanders, Anna Zmarzly, Marta Bueno, Carmen Garde, Ma Estrella Petrina Jáuregui, Cora Jonker, Simona Di Caro, Niamh Keane, Pinal Patel, Sarah-Jane Nelson Hughes, Rachel Lloyd, Arun Abraham, Gerda Garside, Michael Taylor, Jian Wu, Trevor Smith, Charlotte Pither, Michael Stroud, Reena Parmar, Nicola Burch, Sarah Zeraschi, Manpreet Mundi, Denise Jezerski, Pironi L., Steiger E., Joly F., Jeppesen P.B., Wanten G., Sasdelli A.S., Chambrier C., Aimasso U., Mundi M.M., Szczepanek K., Jukes A., Theilla M., Kunecki M., Daniels J., Serlie M., Poullenot F., Cooper S.C., Rasmussen H.H., Compher C., Seguy D., Crivelli A., Santarpia L., Guglielmi F.W., Kozjek N.R., Schneider S.M., Ellegard L., Thibault R., Matras P., Matysiak K., Van Gossum A., Forbes A., Wyer N., Taus M., Virgili N.M., O'Callaghan M., Chapman B., Osland E., Cuerda C., Udvarhelyi G., Jones L., Won Lee A.D., Masconale L., Orlandoni P., Spaggiari C., Diez M.B., Doitchinova-Simeonova M., Serralde-Zuniga A.E., Olveira G., Krznaric Z., Czako L., Kekstas G., Sanz-Paris A., Jauregui M.E.P., Murillo A.Z., Schafer E., Arends J., Suarez-Llanos J.P., Youssef N.N., Brillanti G., Nardi E., Lal S., Crivelli A.N., Muniz H.S., Chapman B.R., Hodgson R., Wallin S., Lasenby K., Brandt C., Boehm V., Bataille J., Billiauws L., Molnar T., Zsilak-Urban M., Izbeki F., Sahin P., Dario M.F., Bertasi V., Regano N., Lidia S., Alfonsi L., Busni D., Gillanders L., Zmarzly A., Bueno M., Garde C., Jonker C., Di Caro S., Keane N., Patel P., Nelson Hughes S.-J., Lloyd R., Abraham A., Garside G., Taylor M., Wu J., Smith T., Pither C., Stroud M., Parmar R., Burch N., Zeraschi S., Mundi M., Jezerski D., Endocrinology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, University of Bologna, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Cleveland Clinic, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Radboud University Medical Center [Nijmegen], Hospices Civils de Lyon (HCL), Città della Salute e della Scienza University-Hospital, Mayo Clinic and Mayo College of Medicine, Rochester, Stanley Dudrick's Memorial Hospital, Partenaires INRAE, University Hospital of Wales, Tel Aviv University [Tel Aviv], University of Lódź, Nottingham University Hospitals NHS Trust [UK], VU University Medical Center [Amsterdam], CHU Bordeaux [Bordeaux], University Hospitals Birmingham NHS Foundation Trust, Aalborg University Hospital, Hospital of the University of Pennsylvania (HUP), Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hospital Universitario Fundacion Favaloro, University of Naples Federico II, Monsignor di Miccoli Hospital, Institute of Oncology - Ljubljana, Institute of Oncology Ljubljana, Centre Hospitalier Universitaire de Nice (CHU Nice), University of Gothenburg (GU), The project of the ESPEN database for Chronic Intestinal Failure was promoted by the ESPEN Executive Committee in 2013, was approved by the ESPEN Council and was supported by an ESPEN grant., University of Bologna/Università di Bologna, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University Hospital of Wales (UHW), Tel Aviv University (TAU), Nottingham University Hospitals NHS Trust (NUH), University of Pennsylvania-University of Pennsylvania, University of Naples Federico II = Università degli studi di Napoli Federico II, and Institute of Oncology [Ljubljana]

Subjects
Parenteral Nutrition, Epidemiology, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, MESH: Intestinal Diseases, Malalties intestinals, 0302 clinical medicine, Indicadors de salut, Medicine, 030212 general & internal medicine, Intestines--Diseases, Nutrition and Dietetics, Intestinal Disease, Short bowel syndrome, Intestinal failure, Health status indicators, 3. Good health, Chronic intestinal failure, Intestine, Intestines, medicine.anatomical_structure, Cohort, 030211 gastroenterology & hepatology, Female, MESH: Intestines, Human, Adult, Short Bowel Syndrome, medicine.medical_specialty, Anastomosis, 03 medical and health sciences, Ileocecal valve, MESH: Cross-Sectional Studies, epidemiology, home parenteral nutrition, intestinal failure, intravenous supplementation, short bowel syndrome, Internal medicine, MESH: Short Bowel Syndrome, Humans, Cross-Sectional Studie, Home parenteral nutrition, MESH: Humans, business.industry, MESH: Adult, medicine.disease, Intravenous supplementation, Intestinal Diseases, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Parenteral nutrition, Cross-Sectional Studies, Jejunostomy, business, MESH: Female, MESH: Parenteral Nutrition
Abstract

Contains fulltext : 244566.pdf (Publisher’s version ) (Closed access) BACKGROUND AND AIMS: The case-mix of patients with intestinal failure due to short bowel syndrome (SBS-IF) can differ among centres and may also be affected by the timeframe of data collection. Therefore, the ESPEN international multicenter cross-sectional survey was analyzed to compare the characteristics of SBS-IF cohorts collected within the same timeframe in different countries. METHODS: The study included 1880 adult SBS-IF patients collected in 2015 by 65 centres from 22 countries. The demographic, nutritional, SBS type (end jejunostomy, SBS-J; jejuno-colic anastomosis, SBS-JC; jejunoileal anastomosis with an intact colon and ileocecal valve, SBS-JIC), underlying disease and intravenous supplementation (IVS) characteristics were analyzed. IVS was classified as fluid and electrolyte alone (FE) or parenteral nutrition admixture (PN). The mean daily IVS volume, calculated on a weekly basis, was categorized as 3 L/day. RESULTS: In the entire group: 60.7% were females and SBS-J comprised 60% of cases, while mesenteric ischaemia (MI) and Crohn' disease (CD) were the main underlying diseases. IVS dependency was longer than 3 years in around 50% of cases; IVS was infused ≥5 days/week in 75% and FE in 10% of cases. Within the SBS-IF cohort: CD was twice and thrice more frequent in SBS-J than SBS-JC and SBS-JIC, respectively, while MI was more frequent in SBS-JC and SBS-JIC. Within countries: SBS-J represented 75% or more of patients in UK and Denmark and 50-60% in the other countries, except Poland where SBS-JC prevailed. CD was the main underlying disease in UK, USA, Denmark and The Netherlands, while MI prevailed in France, Italy and Poland. CONCLUSIONS: SBS-IF type is primarily determined by the underlying disease, with significant variation between countries. These novel data will be useful for planning and managing both clinical activity and research studies on SBS.

Published
2021

23. Personalized circulating tumor DNA in patients with hepatocellular carcinoma: a pilot study

Author

Andreas A. Rostved, C. L. Sørensen, Christina Westmose Yde, C. L. Andersen, T. V. Henriksen, Lise Barlebo Ahlborn, Kristoffer Staal Rohrberg, Finn Cilius Nielsen, Allan Rasmussen, Hans-Christian Pommergaard, and Jane Preuss Hasselby

Subjects
Oncology, Circulating tumor DNA, medicine.medical_specialty, Liver resection, business.industry, Early detection, ctDNA, General Medicine, medicine.disease, digestive system diseases, Mutational analysis, Targeted ngs, NGS, Hepatocellular carcinoma, Internal medicine, Genetics, medicine, In patient, HCC, business, Molecular Biology, Small tumors, Exome sequencing
Abstract

BACKGROUND: Mutational analysis of circulating tumor DNA (ctDNA) can potentially be used for early detection of recurrence after resection for hepatocellular carcinoma (HCC). Mutations from tumor may be identified in plasma as an early sign of recurrence. We conducted a pilot study investigating if somatic mutations could be detected in plasma in patients undergoing liver resection for HCC and in patients with advanced non-resectable HCC.METHODS AND RESULTS: We prospectively included patients undergoing curative liver resection for HCC. Tumor tissue was investigated with whole exome sequencing and preoperative blood samples were evaluated for ctDNA using targeted next-generation sequencing (NGS) with TruSight Oncology 500 including 523 cancer-associated genes. Subsequently, the method was evaluated in patients with advanced HCC. We included eight patients curatively resected for HCC, where tumor tissue mutations were identified in seven patients. However, only in one patient tumor specific mutations were found in the preoperative blood sample. In all three patients with advanced HCC, tumor mutations were detected in the blood.CONCLUSIONS: In patients with resectable HCC, ctDNA could not be reliably detected using the applied targeted NGS method. In contrast, ctDNA was detected in all patients with advanced HCC. Small tumors, tumor heterogeneity and limited sequencing coverage may explain the lack of detectable ctDNA.

Published
2021

24. Incubation Period, Spore Shedding Duration, and Symptoms of Enterocytozoon bieneusi Genotype C Infection in a Foodborne Outbreak in Denmark, 2020

Author

Lasse S Vestergaard, Carl Widstrup Jensen, Sarah Mikkelsen, Luís Alves de Sousa, Lasse Dam Rasmussen, Daniela Michlmayr, Luise Müller, Susanne Schjørring, Steen Ethelberg, Pikka Jokelainen, and Christen Rune Stensvold

Subjects
Adult, Diarrhea, Male, Microbiology (medical), medicine.medical_specialty, Genotype, Denmark, Microsporidiosis, Disease Outbreaks, Infectious Disease Incubation Period, Incubation period, Feces, Internal medicine, Epidemiology, Prevalence, medicine, Humans, Enterocytozoon bieneusi, Phylogeny, Aged, Retrospective Studies, biology, business.industry, Outbreak, Retrospective cohort study, Enterocytozoon, Middle Aged, Spores, Fungal, biology.organism_classification, medicine.disease, Infectious Diseases, Female, medicine.symptom, business
Abstract

Background Microsporidia are rarely reported to cause outbreaks of diarrhea. We describe a foodborne outbreak of microsporidiosis from a workplace canteen in November 2020 in Denmark. Methods A probable case was defined as any person using the canteen between 4 November and 13 December 2020, reporting at least one gastrointestinal symptom, whereas a confirmed case also had an Enterocytozoon bieneusi positive stool sample. A web-based questionnaire was used to collect clinical, epidemiological, and food exposure data. We performed a retrospective cohort study and tested stool samples from affected individuals for bacterial, viral, and parasitic pathogens, including E. bieneusi. Results Altogether, 195 individuals completed the questionnaire. We identified 52 cases (65% male; median age 45 years [range 25–65]). Diarrhea (90%), fatigue (83%), and abdominal pain (79%) were the most commonly reported symptoms. Eight cases were laboratory-confirmed and had E. bieneusi genotype C. The incubation period was between 5 and 12 days, and polymerase chain reaction (PCR)-detectable spore shedding occurred up to 43 days after symptom onset. Disease was associated with consuming food from the workplace canteen on 4 November 2020 (relative risk [RR[, 2.8 [95% confidence interval [CI]: 1.4 – 5.4]) and lunchboxes containing open sandwiches (RR, 3.2 [95% CI: 1.4 – 7.2]) served that day. Conclusions This is the second documented foodborne outbreak of E. bieneusi genotype C-associated diarrhea worldwide. Epidemiological findings advocated an open sandwiches lunchbox from 4 November 2020, as a likely source. E. bieneusi may be an under-reported cause of outbreaks of diarrhea, and testing for it might be useful in foodborne outbreak investigations.

Published
2021

25. A multimodal nutritional intervention after discharge improves quality of life and physical function in older patients – a randomized controlled trial

Author

Anne Wilkens Knudsen, T. Munk, Henrik Hojgaard Rasmussen, Søren Schou Olesen, J.A. Svendsen, Tanja Bak Østergaard, Thordis Thomsen, and Anne Marie Beck

Subjects
Counseling, Male, medicine.medical_specialty, Dietician, Nutritional risk, Nutritional Status, Critical Care and Intensive Care Medicine, Patient Readmission, law.invention, Quality of life, Randomized controlled trial, law, Weight loss, Internal medicine, Weight Loss, Humans, Medicine, Single-Blind Method, Clinical significance, Medical nutrition therapy, Geriatric Assessment, Nutrition, Aged, Nutrition and Dietetics, business.industry, Standard treatment, Malnutrition, Cross-sectoral transition, Length of Stay, medicine.disease, Patient Discharge, Functional Status, Treatment Outcome, Relative risk, Physical function, Quality of Life, Female, Nutrition Therapy, medicine.symptom, business, Subacute Care
Abstract

Summary Background Many older hospitalized patients are at nutritional risk or malnourished and the nutritional condition is often further impaired during hospitalization. When discharged to own home, a “Nutrition Gap” often occurs, causing inadequate dietary intake, and potentially impeded recovery. Previously, cross-sectorial studies of single component nutritional intervention have shown a limited effect on clinically relevant outcomes. We hypothesized that a multimodal nutritional intervention is necessary to elicit a beneficial effect on clinically relevant outcomes. Methods A randomized controlled trial was performed for a period of 16 weeks. At discharge, the intervention group (IG) received dietetic counselling including a recommendation of daily training, an individual nutrition plan and a package containing foods and drinks covering dietary requirements for the next 24 h. Further, a goodie-bag containing samples of protein-rich milk-based drinks were provided. Information regarding recommendations of nutritional therapy after discharge was systematically and electronically communicated to the municipality. The dietician performed telephone follow-ups on day 4 and 30 and a home visit at 16 weeks. The control group (CG) received standard treatment. The primary outcome was readmissions within 6 month, secondary outcomes were Length of Stay (LOS), Health Related Quality of Life (EQ-5D-3L), nutritional status, physical function (30s-CST) and mortality. This trial was registered under ClinicalTrials.gov Identifier no. NCT03488329. Results We included 191 patients (IG: n = 93). No significant difference was seen in readmissions within 6 month (IG: 45% vs. CG: 45%, Risk Ratio (RR): 0.96 0.71–1.31, p = 0.885). At the 16-weeks follow-up more patients in the IG reached at least 75% of energy and protein requirements (82% vs. CG: 61%, p = 0,007). The energy (kcal) and protein intake (g) per kg was significantly higher in the IG (26.4 kcal/kg (±7.4) vs. 22.6 (±7.4), p = 0.0248) (1.1 g/kg (±0.3) vs. 0.9 g/kg (±0.3). Furthermore, significant lower weight loss was seen in IG (0.7 (±4.3) vs. −1.4 (±3.6), p = 0.002). A significant and clinically relevant difference was found in the EQ-5D-3L VAS-score (IG: mean 61.6 ± 16.2 vs. CG: 53.3 ± 19.3, p = 0.011) (Δ14.3 (±15.5) vs. Δ5.6 (±17.2), p = 0.002). A significant difference in mean 30s-CST in IG was also found (7.2 (±4.3) vs. 5.3 (±4.1), p = 0.010). The improvements in physical function were of clinical relevance in both groups, but significantly higher in the IG (Δ4.2 (±4.4) vs. Δ2.2 (±2.5), p = 0.008). In fact, 86% in IG experienced improvements in the 30s-CST compared with 68% in the CG (p = 0.022). LOS was found to be lower at all time points, however not significant (30 days: −3 (−8.5 to 2.5), p = 0.276, 16 weeks: −4 (−10.2 to 2.2, p = 0.204), 6 months: −3 (−9.3 to 3.3, p = 0346)). All-cause mortality was not different between groups, however RR showed a non-significantly 47% reduction at day 30 (0.53 (0.14–2.05, p = 0.499)) and a 17% reduction at 16 weeks (0.83 (0.40–1.73, p = 1.000)) in IG. Per protocol (PP) analysis revealed a non-significant decrease of 32% in readmission at 6 months (RR: 0.68 (0.42–1.08), p = 0.105). Conclusion The present study, using a multimodal nutritional approach, revealed no significant effect on readmissions however a significant positive effect on nutritional status, quality of life and physical function was found. The improvements in quality of life and physical function were of clinical relevance. No significant effect was found on LOS and mortality.

Published
2021

26. Osteosarcopenia and trabecular bone score in patients with type 2 diabetes mellitus

Author

Ricardo Rasmussen Petterle, Carolina Aguiar Moreira, Luciana Muniz Pechmann, and Victoria Zeghbi Cochenski Borba

Subjects
Male, medicine.medical_specialty, Sarcopenia, Waist, type 2 diabetes mellitus, Endocrinology, Diabetes and Metabolism, Osteoporosis, Gastroenterology, Diseases of the endocrine glands. Clinical endocrinology, Absorptiometry, Photon, Trabecular bone score, Bone Density, Diabetes mellitus, Internal medicine, medicine, Humans, Aged, muscle weakness, Bone mineral, Hand Strength, business.industry, Middle Aged, fractures, medicine.disease, RC648-665, osteoporosis, Osteopenia, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Cancellous Bone, Lean body mass, Medicine, Female, business
Abstract

Objective: To evaluate the prevalence of osteosarcopenia and the association of osteosarcopenia with trabecular bone score (TBS) in a group of patients with type 2 diabetes mellitus(T2DMG) compared with a paired control group (CG). Materials and methods: Cross-sectional study with men and women ≥ 50 years recruited by convenience. Patients in both groups answered questionnaires and underwent evaluation of bone mineral density (BMD), handgrip strength (HGS), and TBS. The T2DMG also underwent a gait speed (GS) test. Sarcopenia was defined as low lean mass plus low HGS or GS according to the Foundation for the National Institute of Health Sarcopenia Project, and osteosarcopenia was deemed present when sarcopenia was associated with osteopenia, osteoporosis, or low-energy trauma fractures. Results: The T2DMG (n = 177) and CG (n = 146) had, respectively, mean ages of 65.1 ± 8.2 years and 68.8 ± 11.0 years and 114 (64.4%) and 80 (54.7%) women. T2DMG versus the CG had higher rates of osteosarcopenia (11.9% versus 2.14%, respectively, p = 0.010), sarcopenia (12.9% versus 5.4%, respectively, p < 0.030), and fractures (29.9% versus 18.5%, respectively, p = 0.019), and lower HGS values (24.4 ± 10.3 kg versus 30.9 ± 9.15 kg, respectively, p < 0.001), but comparable BMD values. Mean TBS values were 1.272 ± 0.11 and 1.320 ± 0.12, respectively (p = 0.001). On multivariate analysis, age, greater waist circumference, fractures, and osteoporosis increased the risk of degraded TBS. Osteosarcopenia was associated with diabetes complications (p = 0.03), calcium and vitamin D supplementation (p = 0.01), and all components of osteosarcopenia diagnosis (p < 0.05). Conclusion: Compared with the CG, the T2DMG had a higher prevalence of osteosarcopenia, sarcopenia, and fractures and lower bone quality assessed by TBS.

Published
2021

27. Adipose MDM2 regulates systemic insulin sensitivity

Author

Sarah Søndergård Rasmussen, Blagoy Blagoev, Irina Kratchmarova, Kenneth K.Y. Cheng, Marcus Krüger, Aimin Xu, Lise Madsen, Mohammed-Samir Belmaâti, Si Brask Sonne, Martin Hermansson, Christer S. Ejsing, Jon Petur Gunnarsson, Philip Hallenborg, Even Fjære, Pernille Lauritzen, Benjamin A. H. Jensen, Karsten Kristiansen, and Rasmus Koefoed Petersen

Subjects
Male, Molecular biology, Physiology, Regulator, Adipose tissue, Diseases, Haploinsufficiency, Biochemistry, Fatty Acids, Monounsaturated, Mice, chemistry.chemical_compound, Adipocyte, Adipocytes, Palmitoleic acid, Gene Regulatory Networks, Mice, Knockout, chemistry.chemical_classification, Multidisciplinary, biology, Proto-Oncogene Proteins c-mdm2, Mdm2, Medicine, Female, Cell biology, medicine.medical_specialty, Adipose Tissue, White, Science, Phosphatidate Phosphatase, Diet, High-Fat, Article, NEFA, 3T3-L1 Cells, Internal medicine, Glucose Intolerance, medicine, Animals, Obesity, Fatty acid, medicine.disease, Fatty Liver, Mice, Inbred C57BL, PPAR gamma, Endocrinology, chemistry, biology.protein, Insulin Resistance, Tumor Suppressor Protein p53, Steatosis, Transcription Factors
Abstract

The intimate association between obesity and type II diabetes urges for a deeper understanding of adipocyte function. We and others have previously delineated a role for the tumor suppressor p53 in adipocyte biology. Here, we show that mice haploinsufficient for MDM2, a key regulator of p53, in their adipose stores suffer from overt obesity, glucose intolerance, and hepatic steatosis. These mice had decreased levels of circulating palmitoleic acid [non-esterified fatty acid (NEFA) 16:1] concomitant with impaired visceral adipose tissue expression of Scd1 and Ffar4. A similar decrease in Scd and Ffar4 expression was found in in vitro differentiated adipocytes with perturbed MDM2 expression. Lowered MDM2 levels led to nuclear exclusion of the transcriptional cofactors, MORC2 and LIPIN1, and thereby possibly hampered adipocyte function by antagonizing LIPIN1-mediated PPARγ coactivation. Collectively, these data argue for a hitherto unknown interplay between MDM2 and MORC2/LIPIN1 involved in balancing adipocyte function.

Published
2021

28. Pneumocystis jirovecii pneumonia in liver transplant recipients in an era of routine prophylaxis

Author

Allan Rasmussen, Magda Teresa Thomsen, Andreas Knudsen, Philip B Andreasen, Ranya Houmami, Omid Rezahosseini, Susanne Dam Nielsen, Christian Ross Pedersen, Jenny Dahl Knudsen, Dina L Møller, Neval Ete Wareham, Andreas A. Rostved, and Jørgen A. L. Kurtzhals

Subjects
Adult, medicine.medical_specialty, Opportunistic infection, medicine.medical_treatment, Immunology, Liver transplantation, Pneumocystis carinii, Organ transplantation, law.invention, Randomized controlled trial, law, Internal medicine, Trimethoprim, Sulfamethoxazole Drug Combination, medicine, Humans, Immunology and Allergy, Antibiotic prophylaxis, liver transplantation, business.industry, Pneumonia, Pneumocystis, Incidence (epidemiology), Mortality rate, Original Articles, Antibiotic Prophylaxis, RC581-607, medicine.disease, Pneumocystis jirovecii pneumonia, incidence, Prednisolone, Original Article, prophylaxis, trimethoprim sulfamethoxazole, Immunologic diseases. Allergy, business, medicine.drug
Abstract

Background Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in organ transplant recipients that may be prevented by antibiotic prophylaxis. We aimed to investigate the incidence rate (IR) of PCP and the related hospitalization and mortality rates in liver transplant recipients in an era of routine prophylaxis. Methods We included all adult liver transplant recipients transplanted at Rigshospitalet between January 1, 2011 and October 1, 2019. Microbiology data were obtained from the Danish Microbiology Database (MiBa), a national database containing all data from all Departments of Clinical Microbiology in Denmark receiving samples from both hospitals and general practices. According to local guidelines, PCP prophylaxis was initiated 1 week posttransplantation and discontinued after 6 months or sooner in patients experiencing side effects. Results We included 343 liver transplant recipients with 1153 person‐years of follow‐up (PYFU), of which 269 (78%) received PCP prophylaxis during the first 6 months posttransplantation. Seven (2%) recipients were diagnosed with PCP during follow‐up. In the first 6 months posttransplantation and in 269 transplant recipients who received prophylaxis there were zero PCP events while the IR was 32 (95% confidence interval [CI] 2.9–148) per 1000 PYFU in 74 recipient who did not receive prophylaxis. During 7th to 12th month posttransplantation the IR was 20 (95% CI: 5.5–53) per 1000 PYFU. All seven (100%) recipients diagnosed with PCP were hospitalized, however none died. Conclusions PCP was not detected in liver transplant recipients while on prophylaxis. Though, it worth mentioning that two out of the seven PCP patients received high‐dose prednisolone before the PCP event. All liver transplant recipients with PCP were hospitalized, but none died. Randomized clinical trials to determine the optimal duration of prophylaxis are warranted., We investigated the incidence of Pneumocystis jirovecii pneumonia (PCP) in a cohort of liver transplant recipients in an era with the use of routine PCP prophylaxis. There were no cases of PCP in recipients while on prophylaxis. Furthermore, no case with PCP infection was reported after 15th month posttransplantation. This underlines the need for randomized clinical trials to determine the optimal duration of prophylaxis.

Published
2021

29. Blood culture time to positivity in non-β-hemolytic streptococcal bacteremia as a predictor of infective endocarditis—a retrospective cohort study

Author

David Krus, Bo Nilson, Magnus Rasmussen, Fredrik Kahn, and Torgny Sunnerhagen

Subjects
Male, Microbiology (medical), Infectious Medicine, medicine.medical_specialty, Population, Bacteremia, medicine.disease_cause, Blood culture, Cohort Studies, Medical microbiology, Streptococcal Infections, hemic and lymphatic diseases, Internal medicine, medicine, Humans, heterocyclic compounds, education, neoplasms, Aged, Retrospective Studies, Aged, 80 and over, education.field_of_study, Endocarditis, medicine.diagnostic_test, Clinical Laboratory Medicine, business.industry, Streptococcus, Brief Report, Time to positivity, Retrospective cohort study, Endocarditis, Bacterial, General Medicine, respiratory system, Middle Aged, medicine.disease, Infectious Diseases, Infective endocarditis, Female, business, therapeutics, Cohort study
Abstract

Non-β-hemolytic streptococci (NBHS) cause infective endocarditis (IE) and a short blood culture time to positivity (TTP) is associated with risk of IE in bacteremia with other pathogens. In this retrospective population-based cohort study, we investigate if TTP is associated to IE or mortality. Of 263 episodes with NBHS bacteremia, 28 represented IE and the median TTP did not differ significantly between episodes with IE (15 h) and non-IE (15 h) (p=0.51). TTP was similar among those who survived and those who died within 30 days. However, TTP significantly differed when comparing the different streptococcal groups (p

Published
2021

30. Remarkable high frequency of insecure attachment in children with ADHD persists in a three-year follow-up

Author

Johanne Pereira Ribeiro, Amalie Musaeus, Pernille Darling Rasmussen, Gunnhild Lien, Richard Kirubakaran, Ole Jakob Storebø, and Mette Elmose

Subjects
High rate, medicine.medical_specialty, business.industry, Attachment security, Normal population, Treatment as usual, medicine.disease, Object Attachment, Psychiatry and Mental health, Insecure attachment, Attention Deficit Disorder with Hyperactivity, Cohort, Humans, Medicine, Attention deficit hyperactivity disorder, Observational study, Child, business, Psychiatry, Follow-Up Studies
Abstract

Background Studies have pointed to a complicated and mutual relationship between attention deficit hyperactivity disorder (ADHD) and attachment. In an observational follow-up study conducted in 2015 60 children from 7 years to 12 years recently diagnosed with ADHD were included and assessed according to attachment representation showing 85% of the children to be insecurely attached. Aim The aim of this study was to investigate the stability of this remarkably high frequency of insecure attachment in the same cohort of children. Methods Children previously assessed using the child attachment interview (CAI) when diagnosed with ADHD were contacted three years later for a follow-up CAI assessment. Results At follow-up, 31 children participated in the CAI-interviews. Since their diagnosis with ADHD, the children had received treatment as usual. The CAI-interviews showed a continued high rate of insecure attachment with 90% of the children classifying as insecurely attached compared to expected 38% in the normal population. Of these, the majority of children (77%) were classified as dismissing. Conclusion Our findings suggest that targeting ADHD-symptoms with our current treatment strategies does not in itself improve attachment security. Attachment security may in turn be a factor of importance when evaluating general functioning and prognosis.

Published
2021

31. Physical Activity Advice for Prevention and Rehabilitation of Low Back Pain- Same or Different? A Study on Device-Measured Physical Activity and Register-Based Sickness Absence

Author

Andreas Holtermann, Els Clays, Ole Steen Mortensen, Nidhi Gupta, Charlotte Lund Rasmussen, Ute Bültmann, Jan Hartvigsen, and Public Health Research (PHR)

Subjects
Register based, medicine.medical_specialty, medicine.medical_treatment, Physical activity, Blue-collar workers, Sitting, Lower risk, Leisure Activities, Occupational Therapy, Accelerometry, BENEFITS, Medicine and Health Sciences, medicine, Humans, Activity intensity, Exercise, WORK, RISK, Sickness absence, Low Back Pain/prevention & control, Rehabilitation, business.industry, Compositional data analysis, Low back pain, LIFE, PARADOX, Physical therapy, Sick Leave, medicine.symptom, business, Low Back Pain
Abstract

Purpose We lack knowledge on whether the advice of “being physically active” should be the same for prevention and rehabilitation of low back pain (LBP). Sickness absence is a key outcome for LBP prevention and rehabilitation. We investigated the associations between physical activity and long-term sickness absence (LTSA) among employees with and without LBP. Methods Between 2011 and 2013, 925 Danish employees wore a Actigraph GTX3 accelerometer for 1–5 workdays to measure physical activity and reported LBP in past 7 days. Employees were followed for 4 years to determine their first register-based LTSA event (≥ 6 consecutive weeks). Results Among employees with LBP, increasing moderate-to-vigorous-intensity physical activity at work by 20 min and decreasing the remaining behaviors at work (ie., sitting, standing and light-intensity activity) by 20 min was associated with 38% (95% CI 17%; 63%) higher LTSA risk. Increasing light-intensity activity at work by 20 min and decreasing 20 min from the remaining behaviors was associated with 18% (95% CI 4%; 30%) lower risk. During leisure, increasing moderate-to-vigorous-intensity activity by 20 min or standing by 40 min was associated with 26% (95% CI 3%; 43%) lower and 37% (95% CI 0%; 87%) higher risk, respectively. Among employees without LBP, we found no such associations. Conclusions The physical activity advice ought to be different for LBP prevention and rehabilitation to reduce LTSA risk, and specified by domain and activity intensity. At work, employees with LBP should be advised to spend time on light-intensity physical activity and limit their time on moderate-to-vigorous-intensity physical activity. During leisure, employees should spend time on moderate-to-vigorous-intensity physical activity.

Published
2021

32. Resilience Resources and Emotional and Behavioral Functioning Among Youth and Young Adults with Fetal Alcohol Spectrum Disorder

Author

Jacqueline Pei, Katrina Kully-Martens, Allison McNeil, and Carmen Rasmussen

Subjects
medicine.medical_specialty, Public health, media_common.quotation_subject, Mental health, Developmental psychology, Psychiatry and Mental health, Health psychology, medicine, Normative, Psychological resilience, Early childhood, Young adult, Psychology, Reference group, media_common
Abstract

The purpose of this study was to describe the profile of individual, relational, and contextual resilience resources reported by youth with FASD and their caregivers and examine how these resources related to early childhood adversity, potential protective factors, and concurrent emotional and behavioral functioning. Nineteen youth with FASD (aged 13 to 23 years) and their caregivers (foster or adoptive parents) completed the Child and Youth Resilience Measure (CYRM-28), the Behavioral Assessment System for Children (BASC-2), and a detailed developmental history questionnaire. Youth with FASD were reported to have comparable relational resilience resources to a typically developing reference group, but lower contextual resources compared to the reference group. Caregivers reported youth to have low individual resilience resources, but youth with FASD reported individual resources commensurate with the normative reference group. Early childhood adversity, age, sex, and IQ were not significantly associated with resilience resources. However, earlier age of stable caregiving placement and earlier age at FASD diagnosis were associated with greater caregiver-reported relational and contextual resilience resources. Finally, higher youth- and caregiver-reported individual resources were associated with less mental health symptomology, and higher youth- and caregiver-reported individual and contextual resources were associated with better adaptive functioning behavior. These findings complement previous research documenting the necessity of ensuring early stable relationships for youth with FASD and permitting timely access to diagnostic services. The results also highlight the need to better understand and strengthen individual and contextual resources.

Published
2021

33. Can the Enhanced Liver Fibrosis Score Be Used to Diagnose Children With Liver Fibrosis?

Author

Iben Thusing, Helene Marlies Rasmussen, Per Wittenhagen, Steen Antonsen, and Benjamin Hoffmann-Petersen

Subjects
Liver Cirrhosis, Male, medicine.medical_specialty, Adolescent, Liver fibrosis, Gastroenterology, Internal medicine, medicine, Humans, In patient, Hyaluronic Acid, Child, Normal range, Tissue Inhibitor of Metalloproteinase-1, business.industry, respiratory system, Peptide Fragments, Autosomal Recessive Polycystic Kidney Disease, Reference intervals, Liver, Pediatrics, Perinatology and Child Health, Enhanced Liver Fibrosis Score, Clinical value, Female, business, Biomarkers, Procollagen, Serum markers
Abstract

OBJECTIVES: The noninvasive Enhanced Liver Fibrosis (ELF) score is used in adults with liver fibrosis as a diagnostic aid. The ELF score combines 3 serum markers of extracellular matrix remodeling and fibrogenesis: hyaluronic acid (HA), the N-terminal pro-peptide of collagen type III (PIIINP), and tissue inhibitor of metalloproteinase-1 (TIMP-1). We aimed to evaluate the clinical use of the ELF score in children. METHODS AND RESULTS: A reference interval for the ELF score was established using 343 liver-healthy children ages 6 to 17 years. The median ELF score of 8.9 in healthy children was significantly increased compared with healthy adults. ELF scores increased significantly in both female and male healthy controls with peak levels at puberty, driven by elevated levels of HA and PIIINP likely explained by increased growth. If adult normal values were applied to the group of liver-healthy children, only 6.4% were in the normal range. Prospectively, we analysed ELF scores in patients with possible or confirmed liver fibrosis because of autosomal recessive polycystic kidney disease (ARPKD). All ELF scores in children with ARPKD were within the reference intervals generated from the group of healthy children. CONCLUSIONS: The usual diagnostic cut-off ranges for the ELF score in adults are not applicable; instead age and gender-appropriate cut-off values should be used in children. The clinical value of ELF scores in children is questionable as children during pubertal growth showed elevated ELF scores and patients with ARPKD and liver fibrosis showed normal levels.

Published
2021

34. Increasing severity of early‐onset atopic dermatitis, but not late‐onset, associates with development of aeroallergen sensitization and allergic rhinitis in childhood

Author

Morten Arendt Rasmussen, Hans Bisgaard, Ann-Marie Malby Schoos, Jakob Stokholm, Bo L. Chawes, and Klaus Bønnelykke

Subjects
medicine.medical_specialty, Immunology, specific IgE, Late onset, Gee, Dermatitis, Atopic, medicine, late-onset, Humans, Immunology and Allergy, Prospective Studies, SCORAD, Prospective cohort study, Sensitization, Rhinitis, Asthma, allergic rhinitis, atopic dermatitis, medicine.diagnostic_test, business.industry, Infant, Atopic dermatitis, Allergens, medicine.disease, Rhinitis, Allergic, Dermatology, medicine.anatomical_structure, Cohort, early-onset, business
Abstract

Background: Early exposure to allergens through a defect skin barrier has been proposed as a mechanism for inducing sensitization and development of allergic diseases. We hypothesized that early-onset, severe atopic dermatitis (AD) is associated with development of aeroallergen sensitization and allergic rhinitis. Methods: We included 368 children from the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) at-risk mother-child cohort. AD was diagnosed prospectively based on Hanifin&Rajka's criteria and severity assessed using the Scoring Atopic Dermatitis (SCORAD) index. Early-onset AD was defined as debut ≤1 year, late-onset as debut from 1–6 years. Aeroallergen sensitization and allergic rhinitis were diagnosed at ages 6–7 and 12 years. Associations between early-onset and late-onset AD and allergy endpoints were calculated using general estimating equations (GEE) models to compute the overall odds ratios (OR) for both time points. Results: Early-onset AD (yes/no) and severity (SCORAD) were associated with development of aeroallergen sensitization during childhood; GEE OR = 1.68 [1.08; 2.62], p =.02 and 1.08 [1.03; 1.12], p sensitization =.03 and p-interactionrhinitis

Published
2021

35. VP34.03: Is there an association between the size of the decline in maternal cardiac output in the third trimester and offspring birthweight?

Author

K. Pihl, H. Boyd, A. Andersen, Mads Melbye, J. Wohlfahrt, K. Halse, L.G. Persson, S. Basit, F. Lihme, Jacob Alexander Lykke, K. Lauridsen, and A. Gøth-Rasmussen

Subjects
Cardiac output, medicine.medical_specialty, Radiological and Ultrasound Technology, business.industry, Offspring, Obstetrics, Obstetrics and Gynecology, General Medicine, Third trimester, Reproductive Medicine, Medicine, Radiology, Nuclear Medicine and imaging, Association (psychology), business
Published
2021

36. Cerebrospinal fluid is a significant fluid source for anoxic cerebral oedema

Author

Kristian Nygaard Mortensen, Genaro Olveda, Hajime Hirase, Benjamin T. Kress, Douglas H. Kelley, Guojun Liu, John H. Thomas, Edna R Toro, Amanda M. Sweeney, Poul G. Hjorth, Weiguo Peng, Andrew J. Samson, Erik A. Martens, Rupal I Mehta, Peter A. R. Bork, Yuki Mori, Jeffrey Tithof, Logan Bashford, Ting Du, Humberto Mestre, and Martin Kaag Rasmussen

Subjects
Pathology, medicine.medical_specialty, Resuscitation, Brain Edema, Cerebral edema, Mice, Cerebrospinal fluid, Hypothermia, Induced, Edema, medicine, Animals, Humans, Spreading depolarizations, Osmotic pressure, Hypoxia, Brain, business.industry, Brain, Anoxic cerebral edema, Hypothermia, Cardiac arrest, medicine.disease, Heart Arrest, Original Article, Neurology (clinical), Swelling, medicine.symptom, business, Ex vivo
Abstract

Cerebral oedema develops after anoxic brain injury. In two models of asphyxial and asystolic cardiac arrest without resuscitation, we found that oedema develops shortly after anoxia secondary to terminal depolarizations and the abnormal entry of CSF. Oedema severity correlated with the availability of CSF with the age-dependent increase in CSF volume worsening the severity of oedema. Oedema was identified primarily in brain regions bordering CSF compartments in mice and humans. The degree of ex vivo tissue swelling was predicted by an osmotic model suggesting that anoxic brain tissue possesses a high intrinsic osmotic potential. This osmotic process was temperature-dependent, proposing an additional mechanism for the beneficial effect of therapeutic hypothermia. These observations show that CSF is a primary source of oedema fluid in anoxic brain. This novel insight offers a mechanistic basis for the future development of alternative strategies to prevent cerebral oedema formation after cardiac arrest.

Published
2021

37. The Accuracy of Hemoglobin A1c and Fructosamine Evaluated by Long-Term Continuous Glucose Monitoring in Patients with Type 2 Diabetes Undergoing Hemodialysis

Author

Susanne Rosthøj, Tobias Bomholt, Bo Feldt-Rasmussen, Niels Søndergaard Heinrich, Filip K. Knop, Linda Hilsted, Mads Hornum, Marianne Rix, Anders Larsson, Thomas Almdal, and Morten B. Jørgensen

Subjects
Blood Glucose, medicine.medical_specialty, endocrine system diseases, medicine.medical_treatment, Population, Urology, Renal function, Type 2 diabetes, chemistry.chemical_compound, Renal Dialysis, medicine, Humans, education, Glycemic, Glycated Hemoglobin, education.field_of_study, business.industry, Blood Glucose Self-Monitoring, nutritional and metabolic diseases, Hematology, General Medicine, medicine.disease, Confidence interval, Fructosamine, Diabetes Mellitus, Type 2, chemistry, Nephrology, Hemodialysis, Hemoglobin, business
Abstract

Introduction: The accuracy of hemoglobin A1c (HbA1c) as a glycemic marker in patients with type 2 diabetes (T2D) receiving hemodialysis (HD) remains unknown. To assess accuracy, we compared HbA1c and fructosamine levels with interstitial glucose measured by continuous glucose monitoring (CGM) in patients with T2D receiving HD. Methods: Thirty patients in the HD group and 36 patients in the control group (T2D and an estimated glomerular filtration rate >60 mL/min/1.73 m2) completed the study period of 17 weeks. CGM (Ipro2®, Medtronic) was performed 5 times for periods of up to 7 days (with 4-week intervals) during a 16-week period. HbA1c (mmol/mol), the estimated mean plasma glucose from HbA1c (eMPGA1c [mmol/L]) and fructosamine (μmol/L) was measured at week 17 and compared with mean sensor glucose levels from CGM. Findings: In the HD group, mean sensor glucose was 1.4 mmol/L (95% confidence interval [CI]: 1.0–1.8) higher than the eMPGA1c, whereas the difference for controls was 0.1 mmol/L (95% CI: −0.1–[0.4]; p < 0.001). Adjusted for mean sensor glucose, HbA1c was lower in the HD group (−7.3 mmol/mol, 95% CI: −10.0–[−4.7]) than in the control group (p < 0.001), with no difference detected for fructosamine (p = 0.64). Discussion: HbA1c evaluated by CGM underestimates plasma glucose levels in patients receiving HD. The underestimation represents a clinical challenge in optimizing glycemic control in the HD population. Fructosamine is unaffected by the factors affecting HbA1c and appears to be more accurate for glycemic monitoring. CGM or fructosamine could thus complement HbA1c in obtaining more accurate glycemic control in this patient group.

Published
2021

38. The prognostic significance of HPV, p16, and p53 protein expression in vaginal cancer: A systematic review

Author

Christina Louise Rasmussen, Hanna Kristina Bertoli, Alexander K. Kjaer, Susanne K. Kjaer, Louise T. Thomsen, and Freja Lærke Sand

Subjects
p53, Oncology, medicine.medical_specialty, Vaginal Neoplasms, Improved survival, p16, vaginal cancer, Alphapapillomavirus, Cochrane Library, survival, Disease-Free Survival, Internal medicine, Overall survival, Humans, Medicine, Human papillomavirus, human papillomavirus, P53 expression, Cyclin-Dependent Kinase Inhibitor p16, Vaginal cancer, business.industry, Obstetrics and Gynecology, General Medicine, Prognosis, medicine.disease, P53 protein, Carcinoma, Squamous Cell, Female, prognosis, Tumor Suppressor Protein p53, business, Systematic search
Abstract

Introduction: Human papillomavirus (HPV), p16, and p53 have been investigated as prognostic markers in various HPV-related cancers. Within the field of vaginal cancer, however, the evidence remains sparse. In this systematic review, we have compiled the presently published studies on the prognostic significance of HPV and immunohistochemical expression of p16 and p53 among women with vaginal cancer. Material and methods: We conducted a systematic search of PubMed, Embase, and Cochrane Library to identify relevant studies published until April 2021. We included studies reporting survival after histologically verified vaginal cancers tested for HPV, p16, and/or p53. Survival outcomes included overall survival, disease-free survival, disease-specific survival, and progression-free survival. Results: We included a total of 12 studies. The vast majority of vaginal cancer cases included in each study were squamous cell carcinomas (84%–100%). Seven studies reported survival after vaginal cancer according to HPV status, and the majority of these studies found a tendency towards improved survival for women with HPV-positive vaginal cancer. Three out of four studies reporting survival according to p16 status found an improved survival among women with p16-positive vaginal cancer. For p53, only one of six studies reported an association between p53 expression and survival. Conclusions: This systematic review suggests that women with HPV- and p16-positive vaginal cancer have an improved prognosis compared with those with HPV- or p16-negative vaginal cancer. Results for p53 were varied, and no conclusion could be reached. Only 12 studies could be included in the review, of which most were based on small populations. Hence, further and larger studies on the prognostic impact of HPV, p16, and p53 in vaginal cancer are warranted.

Published
2021

39. Flash glucose monitoring and automated bolus calculation in type 1 diabetes treated with multiple daily insulin injections: a 26 week randomised, controlled, multicentre trial

Author

Birthe Gade-Rasmussen, Thomas Almdal, Kirsten Nørgaard, Dorte Vistisen, Linda Raimond, Anna Lilja Secher, Ulrik Pedersen-Bjergaard, and Ole Lander Svendsen

Subjects
Type 1 diabetes, medicine.medical_specialty, Continuous glucose monitoring, business.industry, Endocrinology, Diabetes and Metabolism, Insulin, medicine.medical_treatment, medicine.disease, Discontinuation, Carbohydrate counting, Diabetes mellitus, Statistical significance, Internal medicine, Internal Medicine, medicine, Bolus (digestion), business
Abstract

We aimed to compare the effects of intermittently scanned continuous glucose monitoring (isCGM) and carbohydrate counting with automated bolus calculation (ABC) with usual care. In a randomised, controlled, open-label trial carried out at five diabetes clinics in the Capital Region of Denmark, 170 adults with type 1 diabetes for ≥1 year, multiple daily insulin injections and HbA1c > 53 mmol/mol (7.0%) were randomly assigned 1:1:1:1 with centrally prepared envelopes to usual care (n = 42), ABC (n = 41), isCGM (n = 48) or ABC+isCGM (n = 39). Blinded continuous glucose monitoring data, HbA1c and patient-reported outcomes were recorded at baseline and after 26 weeks. The primary outcome was change in time in range using isCGM vs usual care. Baseline characteristics were comparable across arms: mean age 47 (SD 13.7) years, median (IQR) diabetes duration 18 (10–28) years and HbA1c 65 (61–72) mmol/mol (8.1% [7.7–8.7%]). Change in time in range using isCGM was comparable to usual care (% difference of 3.9 [−12–23], p = 0.660). The same was true for the ABC and ABC+isCGM arms and for hypo- and hyperglycaemia. Also compared with usual care, using ABC+isCGM reduced HbA1c (4 [95% CI 1, 8] mmol/mol) (0.4 [0.1, 0.7] %-point) and glucose CV (11% [4%, 17%]) and improved treatment satisfaction, psychosocial self-efficacy and present life quality. Treatment satisfaction also improved by using isCGM alone vs usual care. Statistical significance was maintained after multiple testing adjustment concerning glucose CV and treatment satisfaction with ABC+isCGM, and treatment satisfaction with isCGM. Discontinuation was most common among ABC only users, and among completers the ABC was used 4 (2–5) times/day and the number of daily isCGM scans was 5 (1–7) at study end. isCGM alone did not improve time in range, but treatment satisfaction increased in technology-naive people with type 1 diabetes and suboptimal HbA1c. The combination of ABC+isCGM appears advantageous regarding glycaemic variables and patient-reported outcomes, but many showed resistance towards ABC. ClinicalTrials.gov NCT03682237. The study is investigator initiated and financed by the Capital Region of Denmark.

Published
2021

40. Methodological challenges in the analysis of recurrent events for randomised controlled trials with application to cardiovascular events in <scp>LEADER</scp>

Author

Søren Rasmussen, Per Kragh Andersen, Julie K. Furberg, and Henrik Ravn

Subjects
Pharmacology, Statistics and Probability, medicine.medical_specialty, Computer science, Event (computing), media_common.quotation_subject, High mortality, Competing risks, law.invention, Randomized controlled trial, Cardiovascular Diseases, Research Design, law, medicine, Humans, Pharmacology (medical), Function (engineering), Intensive care medicine, Disease burden, media_common
Abstract

Analysis of recurrent events is becoming increasingly popular for understanding treatment effects in randomised controlled trials. The analysis of recurrent events can improve efficiency and capture disease burden compared to standard time-to-first event analyses. However, the added knowledge about the multi-state process comes at the cost of modelling complexity. High mortality rates can complicate matters even more. A case study using data from a randomised controlled trial, LEADER, is presented to highlight interpretation of common methods as well as potential pitfalls when analysing recurrent events in the presence of a competing risk. The presented methods either target features of the underlying intensity functions or marginal traits of a multi-state process which includes terminal events or not. In particular, approaches to handle death as a part of an event and as a competing risk are discussed. A new method targeting the marginal mean function for a composite endpoint, which includes both death as a component and as a competing risk, will be introduced. Finally, recommendations for how to capture meaningful treatment effects in randomised controlled trials when analysing recurrent and terminal events will be made.

Published
2021

41. Supervised exercise therapy compared with no exercise therapy to reverse debilitating effects of androgen deprivation therapy in patients with prostate cancer: a systematic review and meta-analysis

Author

Thomas Bandholm, Pernille Envold Bistrup, Kirsten Birkefoss, Brigitta Rasmussen Villumsen, Marie-Louise Kirkegaard Mikkelsen, Anja Ussing, and Johnny Wejlgaard

Subjects
Androgens/therapeutic use, Male, Cancer Research, medicine.medical_specialty, Urology, Population, MEDLINE, Cochrane Library, Androgen deprivation therapy, Prostate cancer, Quality of life, Internal medicine, Humans, Medicine, education, Exercise, education.field_of_study, business.industry, Prostatic Neoplasms, medicine.disease, Confidence interval, Exercise Therapy, Oncology, Meta-analysis, Androgens, Quality of Life, Prostatic Neoplasms/drug therapy, business
Abstract

Background Androgen deprivation therapy (ADT) in patients with prostate cancer can have several debilitating side effects. Supervised exercise is recommended to ameliorate these negative effects. Objective To systematically evaluate the effect of supervised exercise therapy compared to no exercise therapy in patients with prostate cancer undergoing ADT, primarily according to the patient critical outcomes, ‘disease-specific quality of life’ and ‘walking performance’ measured at end of treatment. Methods We searched PubMed/Medline, Embase, Cochrane Library, Cinahl and Pedro, to identify randomised controlled trials (RCTs), which investigated the effect of supervised exercise therapy compared to no exercise therapy in patients with prostate cancer receiving ADT, last search: June 2021. Two independent reviewers extracted data, and assessed risk of bias using Cochrane Risk of Bias Tool and evaluated the certainty of evidence using the GRADE-method. Results Eigthteen RCTs (n = 1477) comprised patients with prostate cancer stages T1-T4 were included in the meta-analyses. Compared to no exercise therapy, supervised exercise therapy showed clinically relevant improvements in ‘disease-specific quality of life’ and ‘walking performance’. The standardised mean differences were 0.43 (95% confidence interval (CI): 0.29, 0.58) and −0.41 (95% CI: −0.60, −0.22), respectively. The overall certainty of evidence was moderate due to serious risk of bias. Conclusions Evidence of moderate quality shows that supervised exercise therapy probably is superior to no exercise therapy in improving ‘disease-specific quality of life’ and ‘walking performance’ in patients with prostate cancer undergoing ADT. The results apply to all patients receiving androgen deprivation therapy regardless of cancer stage. The results support a strong recommendation for supervised exercise therapy for managing side effects in this population. Protocol registration NKR-38-Focused-questions-PICOs-for-updating1.ashx (sst.dk)

Published
2021

42. Unique Aspects of Asthma in Women

Author

Soeren Malte Rasmussen, Vibeke Backer, Charlotte Suppli Ulrik, Casper Tidemandsen, and Erik Soeren Halvard Hansen

Subjects
Male, Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, medicine.drug_class, media_common.quotation_subject, Fertility, macromolecular substances, Pregnancy, immune system diseases, medicine, Humans, Obesity, Child, Asthma, media_common, Menarche, business.industry, medicine.disease, respiratory tract diseases, Menopause, Transgender hormone therapy, Estrogen, Female, business
Abstract

There are many unique aspects of asthma in women. Compared with men, women go through several hormonal stages over the life span-childhood, menarche, reproductive years, pregnancy, menopause, and postmenopause-and each affects asthma. Onset of asthma in women differs from men. Asthma in women is more often associated with obesity and women are over-represented among patients with severe asthma, including those being prescribed biologic therapies. Asthma affects fertility and pregnancy, and female hormone replacement therapy has been found to affect asthma onset as well as asthma severity. We explore the unique aspects of asthma in women.

Published
2021

43. Behavioral Therapy Teams for Obsessive-Compulsive Disorder: Lessons Learned From a Pilot Randomized Trial in a Community Mental Health Center

Author

Agustin G. Yip, Christina L. Boisseau, Caron Zlotnick, Maria C. Mancebo, and Steven A. Rasmussen

Subjects
Obsessive-Compulsive Disorder, 050103 clinical psychology, medicine.medical_specialty, Community Mental Health Centers, medicine.medical_treatment, Behavioral therapy, Pilot Projects, behavioral disciplines and activities, Coaching, Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Behavior Therapy, law, Intervention (counseling), medicine, Humans, 0501 psychology and cognitive sciences, Depression (differential diagnoses), Cognitive Behavioral Therapy, business.industry, 05 social sciences, Mental health, 030227 psychiatry, Cognitive behavioral therapy, Exposure and response prevention, Clinical Psychology, Treatment Outcome, Physical therapy, business, Psychology
Abstract

Community mental health centers (CMHCs) provide the majority of mental health services for low-income individuals in the United States. Exposure and response prevention (ERP), the psychotherapy of choice for obsessive-compulsive disorder (OCD), is rarely delivered in CMHCs. This study aimed to establish the acceptability and feasibility of testing a behavioral therapy team (BTT) intervention to deliver ERP in CMHCs. BTT consisted of individual information-gathering sessions followed by 12 weeks of group ERP and concurrent home-based coaching sessions. The sample consisted of 47 low-income individuals with OCD who were randomized to receive BTT or treatment as usual (TAU). Symptom severity and quality-of-life measures were assessed at pretreatment, posttreatment, and 3- and 6-month posttreatment. Feasibility of training CMHC staff was partially successful. CMHC therapists successfully completed rigorous training and delivered ERP with high fidelity. However, training paraprofessionals as ERP coaches was more challenging. ERP was feasible and acceptable to patients. BTT participants were more likely than TAU participants to attend their first therapy session and attended significantly more treatment sessions. A large between-group effect size was observed for reduction in OCD symptoms at posttreatment but differences were not maintained across 3- and 6-month follow-ups. For BTT participants, within-group effect sizes reflecting change from baseline to posttreatment were large. For TAU participants, depression scores did not change during the active treatment phase but gradually improved during follow-up. Results support feasibility and acceptability of ERP for this patient population. Findings also underscore the importance of implementation frameworks to help understand factors that impact training professionals.

Published
2021

44. Minimal Clinically Important Differences (MCID) for the Western Ontario Osteoarthritis of the Shoulder Index (WOOS) and the Oxford Shoulder Score (OSS)

Author

Alexander Amundsen, Marc Randall Kristensen Nyring, Bo Sanderhoff Olsen, and Jeppe V. Rasmussen

Subjects
anatomical total shoulder arthroplasty, medicine.medical_specialty, business.industry, Minimal clinically important difference, medicine.medical_treatment, minimal clinically important difference, Outcome measures, General Medicine, General Chemistry, Prom, Osteoarthritis, medicine.disease, Arthroplasty, Patient Related Outcome Measures, humanities, Glenohumeral osteoarthritis, patient reported outcome measures, glenohumeral osteoarthritis, Cohort, Physical therapy, Medicine, Oxford shoulder score, business, Original Research
Abstract

Marc Randall Kristensen Nyring, Bo Sanderhoff Olsen, Alexander Amundsen, Jeppe Vejlgaard Rasmussen Department of Orthopedic Surgery, Herlev and Gentofte Hospital, Hellerup, 2900, DenmarkCorrespondence: Marc Randall Kristensen NyringDepartment of Orthopedic Surgery, Herlev and Gentofte Hospital, University of Copenhagen, Gentofte Hospitalsvej 12, Hellerup, 2900, DenmarkTel +45 38673840Email marc.randall.kristensen.nyring@regionh.dkBackground: The minimal clinically important difference (MCID) is an important instrument in the interpretation of changes in patient-reported outcome measures (PROM). To our knowledge, no MCID of the Western Ontario Osteoarthritis of the Shoulder Index (WOOS) score has ever been reported and no studies have reported an MCID for the Oxford Shoulder Score (OSS) based on patients with glenohumeral osteoarthritis, treated with an anatomical total shoulder arthroplasty (aTSA). The aim of this study was to determine MCID for WOOS and OSS in a cohort of patients with glenohumeral osteoarthritis treated with an aTSA.Methods: All patients treated with an aTSA for glenohumeral osteoarthritis at our institution between March 2017 and February 2019 were included. Each patient completed the WOOS and the OSS preoperatively and one year postoperatively. At one year, the patients were asked to rate their overall improvement on a 7-point scale. We used an anchor-based method as our primary method to calculate the MCID, supported by two different distribution-based methods.Results: A total of 45 primary aTSA were included. The MCID of WOOS was 12.3 according to the anchor-based method and 14.2 and 10.3 according to the two distribution-based methods. The MCID of OSS was 4.3 according to the anchor-based method and 5.8 and 4.3 according to the two distribution-based methods.Conclusion: The anchor-based method is considered superior to the distribution-based method, and therefore we advocate to use this as MCID. For patients with glenohumeral osteoarthritis treated with an aTSA, the MCID values were 12.3 points for WOOS and 4.3 points for OSS. To our knowledge, this is the first study to report a MCID value for WOOS and the first study to report a MCID value for OSS in this subgroup of patients.Keywords: minimal clinically important difference, glenohumeral osteoarthritis, anatomical total shoulder arthroplasty, patient reported outcome measures

Published
2021

45. Practices and pitfalls in medication adherence in hemodialysis settings – a focus-group study of health care professionals

Author

Trine Mechta Nielsen, Thordis Thomsen, Nina Schjerning, Gudrun Kaldan, Mads Hornum, and Bo Feldt-Rasmussen

Subjects
medicine.medical_specialty, Attitude of Health Personnel, Health Personnel, media_common.quotation_subject, Psychological intervention, Patient and public involvement, Renal Dialysis, Internal medicine, Qualitative research, Health care, Humans, Medicine, Patient Reported Outcome Measures, Medication adherence, media_common, Delegation, Clinical Laboratory Techniques, business.industry, Research, Gold standard, Professional-Patient Relations, Focus Groups, Focus group, Diseases of the genitourinary system. Urology, Nephrology, Content analysis, Family medicine, Hemodialysis, RC870-923, Deprescribing, business
Abstract

Background Medication nonadherence is common among patients with hemodialysis, leading to poorer patient outcomes. Health care professionals have an important role in assessing risk of nonadherence and intervening to support adherence. The aim of this study was to explore physicians’ and nurses’ current medication adherence practices in hemodialysis settings. Method A generic qualitative design with inductive content analysis and focus group methodology. Focus groups with health care professionals were conducted in four Nephrology Centers, representing three different regions of Denmark. An interview guide was developed in collaboration with 3 patient representatives. Results Six focus group interviews involving a total of forty-two health care professionals were conducted. Five main categories were identified; Laboratory tests are the “gold standard” for assessing adherence, suggesting that abnormal results motivated investigation of adherence, Varying practices for supporting adherence, alluding to the impact of individual clinician priority and preference on choice of adherence interventions, Unclear allocation of roles and responsibility, specifically referring to uncertainty in the delegation of roles between physicians and nurses, Navigating time and resource limitations, intimating the resources needed to support medication adherence and Suggestions for future strategies. Conclusions We suggest implementing systematic use of validated patient-reported outcome measures for assessing adherence and deprescribing tools to support adherence, as these instruments might identify the patients who are in most need of support and promote patient adherence to their prescribed medications. The findings also point to a need for interdisciplinary clarification of roles and responsibilities regarding medication adherence, with the aim of building a strong collaborative partnership between professions.

Published
2021

46. Angiotensin II for Critically Ill Patients With Shock After Heart Transplant

Author

Nathan S. Cutler, Bridget M. Rasmussen, Ashish Khanna, Joseph F. Bredeck, and Adrian L. Lata

Subjects
medicine.medical_specialty, business.industry, medicine.medical_treatment, Organ dysfunction, 030204 cardiovascular system & hematology, medicine.disease, Angiotensin II, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, Blood pressure, 030202 anesthesiology, Heart failure, Ventricular assist device, Internal medicine, Shock (circulatory), Vasoplegia, medicine, Cardiology, medicine.symptom, Vasoplegic syndrome, Cardiology and Cardiovascular Medicine, business
Abstract

Patients undergoing heart transplant are at high risk for vasodilatory shock in the postoperative period, due to a combination of vascular dysfunction from end-stage heart failure and inflammatory response to cardiopulmonary bypass and, increasingly, long-term exposure to nonpulsatile blood flow in those who have received a left ventricular assist device as a bridge to transplant. Patients who have this vasoplegic syndrome, which may be refractory to traditional agents used in the treatment of shock, are vulnerable to organ dysfunction and death. Angiotensin II (ANG-2) is of increasing interest as an adjunct to traditional therapy, both for improvement in blood pressure and for sparing the use of high-dose catecholamine vasopressors. This case series describes the use of ANG-2 in 4 clinical scenarios for the treatment of shock due to heart transplant surgery, supporting its use in this role and justifying further prospective studies to clarify the appropriate place for ANG-2 in the hierarchy of adjunctive therapies.

Published
2021

47. Cause of Death Among Cardiac Patients With and Without Anxiety

Author

Trine Bernholdt Rasmussen, Charlotte Brun Thorup, Martin Balslev Jørgensen, Knud Juel, Jesper Hastrup Svendsen, Lars Thrysoee, Rikke Elmose Mols, Selina Kikkenborg Berg, Britt Borregaard, Ola Ekholm, Anne Vinggaard Christensen, and Pernille Fevejle Cromhout

Subjects
Advanced and Specialized Nursing, Heart Diseases/complications, medicine.medical_specialty, business.industry, Mortality rate, Disease, Anxiety, Hospital Anxiety and Depression Scale, Logistic regression, Anxiety Disorders, Mental distress, Increased risk, Internal medicine, Cause of Death, Surveys and Questionnaires, Medicine, Humans, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Cause of death
Abstract

BACKGROUND: Mental distress is reported internationally among patients with cardiac disease. A Danish survey found that 25% of patients with cardiac disease experienced symptoms indicating anxiety and that anxiety was associated with an increased risk of death.AIM: The aims of this study were to (1) compare cause of death patterns among deceased cardiac patients with anxiety to those without anxiety and (2) examine the association between anxiety symptoms and specific causes of death.METHODS: We used data from the DenHeart survey to evaluate symptoms of anxiety at discharge by using the Hospital Anxiety and Depression Scale. Data on mortality in the 3 years after discharge and cause of death according to International Classification of Diseases-10 classification came from national registers. Cause of death was compared between patients with and without anxiety using χ2 tests. The association between symptoms of anxiety and cause of death was investigated using logistic regression.RESULTS: Of 12 913 patients included, a total of 1030 (8%) died within 3 years. After 1 year, 4% of patients with anxiety symptoms had died versus 2% of patients without; after 3 years, the proportions were 9% versus 8%, respectively. Almost all died of natural causes irrespective of anxiety symptoms. No statistically significant differences were found regarding the cause of death between patients with and without anxiety.CONCLUSION: Despite higher mortality rates in patients with cardiac disease with anxiety symptoms, the pattern of cause of death was identical for patients with cardiac disease with and without anxiety symptoms. It seems that an acceleration of morbid processes leading to mortality is more likely than a difference in cause of death. However, further research is needed to better understand the behavioral and pathophysiological processes that cause the higher mortality seen among patients reporting symptoms of anxiety.

Published
2022

48. Impact of cardiovascular risk factors and genetics on 10-year absolute risk of dementia: risk charts for targeted prevention

Author

Katrine L. Rasmussen, Ida Juul Rasmussen, Ruth Frikke-Schmidt, Anne Tybjærg-Hansen, and Børge G. Nordestgaard

Subjects
medicine.medical_specialty, Epidemiology, Population, Psychological intervention, Genome-wide association study, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Risk Factors, Diabetes mellitus, Genetics, Humans, Medicine, Dementia, AcademicSubjects/MED00200, 030212 general & internal medicine, education, Cardiovascular risk factors, Aged, Aged, 80 and over, education.field_of_study, Framingham Risk Score, business.industry, Absolute risk reduction, Epidemiology and Prevention, medicine.disease, Cardiovascular Diseases, Heart Disease Risk Factors, Cardiology and Cardiovascular Medicine, business
Abstract

Aims Dementia is a major global challenge for health and social care in aging populations. A third of all dementia may be preventable due to cardiovascular risk factors. Intensive multi-domain intervention trials targeting primarily cardiovascular risk factors show improved cognitive function in people at risk. Such interventions will, however, be expensive to implement in all individuals at risk and will represent unrealistic economic tasks for most societies. Therefore, a risk score identifying high-risk individuals is warranted. Methods and results In 61 664 individuals from two prospective cohorts of the Danish general population, we generated 10-year absolute risk scores for all-cause dementia from cardiovascular risk factors and genetics. In both sexes, 10-year absolute risk of all-cause dementia increased with increasing age, number of apolipoprotein E (APOE) ɛ4 alleles, number of genome-wide association studies (GWAS) risk alleles, and cardiovascular risk factors. The highest 10-year absolute risks of all-cause dementia seen in smoking women with diabetes, low education, APOE ɛ44 genotype, and 22–31 GWAS risk alleles were 6%, 23%, 48%, and 66% in those aged 50–59, 60–69, 70–79, and 80–100, respectively. Corresponding values for men were 5%, 19%, 42%, and 60%, respectively. Conclusion Ten-year absolute risk of all-cause dementia increased with age, APOE ɛ4 alleles, GWAS risk alleles, diabetes, low education, and smoking in both women and men. Ten-year absolute risk charts for dementia will facilitate identification of high-risk individuals, those who likely will benefit the most from an early intervention against cardiovascular risk factors., Graphical Abstract Graphical Abstract

Published
2020

49. Stroke prevention in patients from Latin American countries with non‐valvular atrial fibrillation: Insights from the GARFIELD‐AF registry

Author

Jerjes-Sanchez C., Corbalan R., Barretto A. C. P., Luciardi H. L., Allu J., Illingworth L., Pieper K. S., Kayani G., Fitzmaurice D. A., Goto S., Hacke W., Mantovani L. G., Turpie A. G. G., Gersh B. J., Gibbs H., Brodmann M., Cools F., Connolly S. J., Spyropoulos A., Eikelboom J., Hu D., Jansky P., Nielsen J. D., Ragy H., Raatikainen P., Le Heuzey J. -Y., Darius H., Keltai M., Kakkar S., Sawhney J. P. S., Agnelli G., Ambrosio G., Koretsune Y., Diaz C. J. S., ten Cate H., Atar D., Stepinska J., Panchenko E., Lim T. W., Jacobson B., Oh S., Vinolas X., Rosenqvist M., Steffel J., Angchaisuksiri P., Parkhomenko A., Al Mahmeed W., Chen K. N., Zhao Y. S., Zhang H. Q., Chen J. Z., Cao S. P., Wang D. W., Yang Y. J., Li W. H., Yin Y. H., Tao G. Z., Yang P., Chen Y. M., He S. H., Wang Y., Fu G. S., Li X., Wu T. G., Cheng X. S., Yan X. W., Zhao R. P., Chen M. S., Xiong L. G., Chen P., Jiao Y., Guo Y., Xue L., Wang F. Z., Li H., Yang Z. M., Bai C. L., Chen J., Chen J. Y., Chen X., Feng S., Fu Q. H., Gao X. J., Guo W. N., He R. H., He X. A., Hu X. S., Huang X. F., Li B., Li J., Li L., Li Y. H., Liu T. T., Liu W. L., Liu Y. Y., Lu Z. C., Luo X. L., Ma T. Y., Peng J. Q., Sheng X., Shi X. J., Sun Y. H., Tian G., Wang K., Wang L., Wu R. N., Xie Q., Xu R. Y., Yang J. S., Yang L. L., Yang Q., Ye Y., Yu H. Y., Yu J. H., Yu T., Zhai H., Zhan Q., Zhang G. S., Zhang Q., Zhang R., Zhang Y., Zheng W. Y., Zhou B., Zhou Z. H., Zhu X. Y., Jadhav P., Durgaprasad R., Ravi Shankar A. G., Rajput R. K., Bhargava K., Sarma R., Srinivas A., Roy D., Nagamalesh U. M., Chopda M., Kishore R., Kulkarni G., Chandwani P., Pothiwala R. A., Padinhare Purayil M., Shah S., Chawla K., Kothiwale V. A., Raghuraman B., Vijayaraghavan G., Vijan V. M., Bantwal G., Bisne V., Khan A., Gupta J. B., Kumar S., Jain D., Abraham S., Adak D., Barai A., Begum H., Bhattacharjee P., Dargude M., Davies D., Deshpande B., Dhakrao P., Dhyani V., Duhan S., Earath M., Ganatra A., Giradkar S., Jain V., Karthikeyan R., Kasala L., Kaur S., Krishnappa S., Lawande A., Lokesh B., Madarkar N., Meena R., More P., Naik D., Prashanth K., Rao M., Rao N. M., Sadhu N., Shah D., Sharma M., Shiva P., Singhal S., Suresh S., Vanajakshamma V., Panse S. G., Kanamori S., Yamamoto K., Kumagai K., Katsuda Y., Sadamatsu K., Toyota F., Mizuno Y., Misumi I., Noguchi H., Ando S., Suetsugu T., Minamoto M., Oda H., Shiraishi K., Adachi S., Chiba K., Norita H., Tsuruta M., Koyanagi T., Ando H., Higashi T., Okada K., Azakami S., Komaki S., Kumeda K., Murayama T., Matsumura J., Oba Y., Sonoda R., Goto K., Minoda K., Haraguchi Y., Suefuji H., Miyagi H., Kato H., Nakamura T., Nandate H., Zaitsu R., Fujiura Y., Yoshimura A., Numata H., Ogawa J., Tatematsu H., Kamogawa Y., Murakami K., Wakasa Y., Yamasawa M., Maekawa H., Abe S., Kihara H., Tsunoda S., Saito K., Fudo T., Obunai K., Tachibana H., Oba I., Kuwahata T., Higa S., Gushiken M., Eto T., Yoshida H., Ikeda D., Ishizawa M., Nakatsuka M., Murata K., Ogurusu C., Shimoyama M., Akutsu M., Takamura I., Hoshino F., Yokota N., Iwao T., Tsuchida K., Takeuchi M., Hatori Y., Kitami Y., Nakamura Y., Oyama R., Ageta M., Go Y., Mishima K., Unoki T., Morii S., Shiga Y., Sumi H., Nagatomo T., Sanno K., Fujisawa K., Atsuchi Y., Nagoshi T., Seto T., Tabuchi T., Kameko M., Nii K., Oshiro K., Takezawa H., Nagano S., Miyamoto N., Iwaki M., Fujii M., Okawa M., Abe M., Saito T., Mito T., Nagao K., Minami J., Mita T., Sakuma I., Taguchi T., Marusaki S., Doi H., Tanaka M., Fujito T., Matsuta M., Kusumoto T., Kakinoki S., Ashida K., Yoshizawa N., Agata J., Arasaki O., Manita M., Ikemura M., Fukuoka S., Murakami H., Matsukawa S., Hata Y., Taniguchi T., Ko T., Kubo H., Imamaki M., Akiyama M., Inagaki M., Odakura H., Ueda T., Katsube Y., Nakata A., Watanabe H., Techigawara M., Igarashi M., Taga K., Kimura T., Tomimoto S., Shibuya M., Nakano M., Ito K., Seo T., Hiramitsu S., Hosokawa H., Hoshiai M., Hibino M., Miyagawa K., Horie H., Sugishita N., Soma A., Neya K., Yoshida T., Mizuguchi M., Ishiguro M., Minagawa T., Wada M., Mukawa H., Okuda F., Nagasaka S., Abe Y., Adachi T., Akahane K., Amano T., Aoki K., Aoyama T., Arai H., Arima S., Arino T., Asano H., Asano T., Azuma J., Baba T., Betsuyaku T., Chibana H., Date H., Doiuchi J., Emura Y., Endo M., Fujii Y., Fujiki R., Fujisawa A., Fujisawa Y., Fukuda T., Fukui T., Furukawa N., Furukawa T., Furumoto W., Goto T., Hamaoka M., Hanazono N., Hasegawa K., Hatsuno T., Hayashi Y., Higuchi K., Hirasawa K., Hirayama H., Hirose M., Hirota S., Honda M., Ido T., Iiji O., Ikeda H., Ikeda K., Ikeoka K., Imaizumi M., Inaba H., Inoue T., Iseki F., Ishihara A., Ishioka N., Ito N., Iwase T., Kakuda H., Kamata J., Kanai H., Kanda H., Kaneko M., Kano H., Kasai T., Kato T., Kato Y., Kawada Y., Kawai K., Kawakami K., Kawakami S., Kawamoto T., Kawano S., Kim J., Kira T., Kitazawa H., Kitazumi H., Kito T., Kobayashi T., Koeda T., Kojima J., Komatsu H., Komatsu I., Koshibu Y., Kotani T., Kozuka T., Kumai Y., Kumazaki T., Maeda I., Maeda K., Maruyama Y., Matsui S., Matsushita K., Matsuura Y., Mineoi K., Mitsuhashi H., Miura N., Miyaguchi S., Miyajima S., Miyamoto H., Miyashita A., Miyata S., Mizuguchi I., Mizuno A., Mori T., Moriai O., Morishita K., Murai O., Nagai S., Nagata E., Nagata H., Nakagomi A., Nakahara S., Nakamura M., Nakamura R., Nakanishi N., Nakayama T., Nakazato R., Nanke T., Nariyama J., Niijima Y., Niinuma H., Nishida Y., Nishihata Y., Nishino K., Nishioka H., Nishizawa K., Niwa I., Nomura K., Nomura S., Nozoe M., Ogawa T., Ohara N., Okada M., Okamoto K., Okita H., Okuyama M., Ono H., Ono T., Pearce Y. O., Oriso S., Ota A., Otaki E., Saito Y., Sakai H., Sakamoto N., Sakamoto Y., Samejima Y., Sasagawa Y., Sasaguri H., Sasaki A., Sasaki T., Sato K., Sawano M., Seki S., Sekine Y., Seta Y., Sezaki K., Shibata N., Shiina Y., Shimono H., Shimoyama Y., Shindo T., Shinohara H., Shinohe R., Shinozuka T., Shirai T., Shiraiwa T., Shozawa Y., Suga T., Sugimoto C., Suzuki K., 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., 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 G. -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., Kim H. J., Kim J. S., Kim J. A., Kim K. T., Kim M. S., Kim S. H., Kim Y. -I., Lee 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., Noh I. K., 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., Karatas S. K., Okutucu S., Ozcelik E., Quisi A., Sag H., Sahiner L., Sayin B. Y., Seker T., Alkan D. U., Yildirim E., Yildirim R., Yilmaz F., Yuksekdag V., Vensentini N., Ingaramo A. C., Sambadaro G. A., Caputi V. F., Berman S. G., Dragotto P., Kleiban A. J., Centurion N., Giacomi G., Guerrero R. A. 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., Vilamajo O. A. G., Ferroni F., Alaguibe E. D., D'Amelio A. 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., Berra F. C., Costabel J. P., Costamagna O. J. A., Damonte A. A., De Urquiza I. N., Diez F., Eden M. F., Fanuele M., Voena F. F., Torres M. F., Funosas C., Giacomi M. P., Gimenez C. H., Gurfinkel E. P., Had M. D. L. 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., Prados G. P., Pontoriero J., Potito R. N., Ricotti C., Rodriguez M. A., Rolandi F., Palladino M. E. S., 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., Filho D. C. S., Jaber J., Armaganijan D., Neto J. F., Steffens A., de Souza W. K. S. B., de Souza Neto J. D., Ribeiro J. M., Teixeira M. S., Rossi P. R. F., Pires L., Moreira D., Jorge J. C. M., Filho A. M. L., Bodanese L. C., Montera M. W., Del Carlo C. H., Rodrigues T. D. R., da Costa F. A. A., Lopes A., Lopes R., Araujo G. R., Manenti E. R. F., Saraiva J. F. 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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. 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Subjects
Registrie, Male, Latin Americans, 030204 cardiovascular system & hematology, outcomes, 0302 clinical medicine, Drug Prescription, Retrospective Studie, Risk Factors, Atrial Fibrillation, Antithrombotic, Prospective Studies, Registries, 030212 general & internal medicine, Practice Patterns, Physicians', Stroke, Anticoagulant, Atrial fibrillation, General Medicine, Middle Aged, Treatment Outcome, Stroke prevention, outcome, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, Human, medicine.medical_specialty, medicine.drug_class, Clinical Investigations, Hemorrhage, antithrombotic treatment, Drug Prescriptions, 03 medical and health sciences, Internal medicine, medicine, Humans, Mexico, Aged, Retrospective Studies, Fibrillation, business.industry, Risk Factor, Anticoagulants, South America, medicine.disease, Drug Utilization, Clinical trial, Prospective Studie, Latin American, antithrombotic treatment, atrial fibrillation, Latin American, outcomes, business
Abstract

Author(s): Jerjes-Sanchez, Carlos; Corbalan, Ramon; Barretto, Antonio CP; Luciardi, Hector L; Allu, Jagan; Illingworth, Laura; Pieper, Karen S; Kayani, Gloria; GARFIELD-AF Investigators | Abstract: BackgroundAtrial fibrillation (AF) is an important preventable cause of stroke. Anticoagulation (AC) therapy can reduce this risk. However, prescribing patterns and outcomes in patients with non-valvular AF (NVAF) from Latin American countries are poorly described.MethodsUsing data from the Global Anticoagulant Registry in the FIELD-AF (GARFIELD-AF), we examined the stroke prevention strategies and the 1-year outcomes in patients from four Latin American countries: Argentina, Brazil, Chile, and Mexico.ResultsA total of 4162 patients (2010-2014) were included in this analysis. At the time of AF diagnosis, 39.9% of patients were prescribed vitamin K antagonists (VKA) ± antiplatelet (AP) therapy, 21.8% non-VKA oral anticoagulant (NOAC) ± AP, 24.1% AP only and 14.1% no antithrombotic treatment. The proportion of moderate-high risk patients receiving no AC therapy at participating centers was highest in Mexico (46.4%) and lowest in Chile (14.3%). During 1-year follow-up, the rates of all-cause mortality, stroke/SE and major bleeding were: 5.77 (95% CI) (5.06-6.56), 1.58 (1.23-2.02), and 0.99 (0.72-1.36) and per 100 person-years, respectively, which are higher than the global rates across all countries in GARFIELD-AF. Unadjusted rates of all-cause mortality were highest in Argentina, 6.95 (5.43-8.90), and lowest in Chile, 4.01 (2.92-5.52).ConclusionsGARFIELD-AF results describes the marked variation in the baseline characteristics and patterns of antithrombotic treatments in patients with NVAF in four Latin American countries. Over one-third of patients with a moderate-to-high risk of stroke received no AC therapy, highlighting the need for improved management of patients according to national guideline. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.

Published
2019

50. Genotype–phenotype associations in PPGLs in 59 patients with variants in SDHX genes

Author

Line Borgwardt, Åse Krogh Rasmussen, Ailsa Maria Main, Birgitte Grønkær Toft, Ulla Feldt-Rasmussen, and Maria Rossing

Subjects
Proband, Oncology, medicine.medical_specialty, Genotype, phenotype, SDHB, genotype, Endocrinology, Diabetes and Metabolism, SDHA, 030209 endocrinology & metabolism, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Germline, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Internal Medicine, medicine, PPGL, Gene, lcsh:RC648-665, business.industry, Research, ppgl, Phenotype, 030220 oncology & carcinogenesis, SDHD, business
Abstract

Phaeochromocytomas and paragangliomas (PPGLs) are tumours of the adrenal medulla and extra-adrenal sympathetic nervous system which often secrete catecholamines. Variants of the SDHX (SDHA, -AF2, -B, -C, -D) genes are a frequent cause of familial PPGLs. In this study from a single tertiary centre, we aimed to characterise the genotype–phenotype associations in patients diagnosed with germline variants in SDHX genes. We also assessed whether systematic screening of family members resulted in earlier detection of tumours. The study cohort comprised all individuals (n = 59) diagnosed with a rare variant in SDHX during a 13-year period. Patient- and pathology records were checked for clinical characteristics and histopathological findings. We found distinct differences in the clinical and histopathological characteristics between genetic variants in SDHB. We identified two SDHB variants with distinct phenotypical patterns. Family screening for SDHB variants resulted in earlier detection of tumours in two families. Patients with SDHA, SDHC and SDHD variants also had malignant phenotypes, underlining the necessity for a broad genetic screening of the proband. Our study corroborates previous findings of poor prognostic markers and found that the genetic variants and clinical phenotype are linked and, therefore, useful in the decision of clinical follow-up. Regular tumour screening of carriers of pathogenic variants may lead to an earlier diagnosis and expected better prognosis. The development of a combined algorithm with clinical, genetic, morphological, and biochemical factors may be the future for improved clinical risk stratification, forming a basis for larger multi-centre follow up studies.

Published
2020

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