Bir Kas-İskelet Sistemi Patolojisi: “Kırılganlık (Frailty) Sendromu”
Özet
Kırılganlık Sendromu (KS), genellikle yaşlı bireylerde iki veya daha fazla fizyolojik sistemde biriken kayıplar sonucunda, vücudun fiziksel, biyolojik ve psikojenik travmalara karşı direnç kaybetmesi ile ortaya çıkan bir biyolojik sendromdur. Bu sendrom, özellikle kas-iskelet sistemi rahatsızlıkları ile ilişkilidir ve yaşlılarda yaygın bir sorundur. KS; kuvvet kaybı, yavaş yürüme, bitkinlik ve düşük fiziksel aktivite gibi belirtilerle karakterize olup, bireyleri savunmasız hale getirir. Tanı ve Yaygınlık: KS tanısı klinik belirtilere dayanmakla birlikte, çeşitli tanı kriterleri ve kırılganlık ölçüm endeksleri kullanılarak teşhis edilir. Bu sendromun yaygınlığı yaşa bağlı olarak artar. Özellikle romatizmal hastalıklar, osteoartrit (OA) ve romatoid artrit (RA) gibi rahatsızlıklar KS ile yakın ilişkilidir. Bu hastalıklarda fiziksel işlevsizlik ve sarkopeni gibi sorunlar kırılganlığın ilerlemesine yol açar. KS’nin Biyolojik Temelleri ve İlişkili Rahatsızlıklar: Kronik enflamasyon, düşük kas kütlesi ve güçsüzlük gibi belirtiler KS’nin biyolojik temelini oluşturur. Sarkopeni (kas kaybı) ve osteoporoz (kemik erimesi), KS’nin önemli bileşenlerindendir. Romatoid artrit, osteoartrit ve sistemik lupus eritematoz gibi otoimmün hastalıklar da KS ile ilişkilidir ve bu hastalıklar kırılganlığın yayılmasına katkı sağlar. Bu makale, yaşlanmaya bağlı kas-iskelet sistemi rahatsızlıkları ile kırılganlık sendromu arasındaki ilişkiyi klinik ve biyokimyasal yönleriyle detaylandırmakta ve tedavi yaklaşımlarını ele almaktadır.
Frailty Syndrome (FS) is a biological condition that typically arises in elderly individuals due to accumulated losses in two or more physiological systems, leading to decreased resistance to physical, biological, and psychogenic stressors. It is especially associated with musculoskeletal disorders and is a widespread issue among older adults. FS is characterized by symptoms such as muscle weakness, slow walking speed, fatigue, and low physical activity, making individuals more vulnerable. Diagnosis and Prevalence: The diagnosis of FS is based on clinical symptoms, though various diagnostic criteria and frailty measurement indexes are used to assess it. The prevalence of frailty increases with age. Frailty is closely linked to rheumatic diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA), where physical dysfunction and sarcopenia (muscle loss) contribute to the progression of frailty. Biological Foundations and Related Disorders: Chronic inflammation, low muscle mass, and weakness are key biological factors underlying FS. Sarcopenia and osteoporosis (bone loss) are major components of frailty. Autoimmune diseases such as rheumatoid arthritis, osteoarthritis, and systemic lupus erythematosus are associated with FS and contribute to its widespread occurrence.
The article details the relationship between age-related musculoskeletal disorders and frailty syndrome from clinical and biochemical perspectives, while also addressing treatment approaches.
Referanslar
Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–M56
Walston J, Hadley EC, Ferrucci L, et al. Research agenda for frailty in older adults: toward a better understanding of physiology and etiology: summary from the American geriatrics society/national institute on aging research conference on frailty in older adults. J Am Geriatr Soc. 2006;54:991–1001.
Rockwood K, Mitnitski A. Frailty defined by deficit accumulation and geriatric medicine defined by frailty. Clin Geriatr Med. 2011;27:17–2614.
Choi J, Ahn A, Kim S, Global prevalence of physical frailty by Fried’s criteria in community-dwelling elderly with national population based surveys. J Am Med Dir Assoc. 2015;16(7):548–50.
Michel JP, Cruz-Jentoft AJ, Cederholm T. Frailty, exercise and nutrition. Clin Geriatr Med. 2015;31(3):375.87
Alvarado BE, Zunzunegui MV, Beland F,. Life course social and health conditions linked to frailty in Latin American older men and women. J Gerontol A Biol Sci Med Sci. 2008;63(12):1399–406.
Shinkai S, Yoshida H, Taniguchi Y, et al. Public health approach to preventing frailty in the community and its effect on healthy aging in Japan. Geriatr Gerontol Int. 2016;(16 Suppl 1):87–97.
Collard RM, Boter H, Schoevers RA, Prevalence of frailty in community-dwelling older persons: a systematic review. J Am Geriatr Soc. 2012;60(8):1487–1492.
Mulasso A, Roppolo M, Giannotta F, Associations of frailty and psychosocial factors with autonomy in daily activities: a cross-sectional study in Italian community-dwelling older adults. Clin Interv Aging.2016;11(11):37,45
Wick JY. Understanding frailty in the geriatric population. Consult Pharm. 2011;26(9):634–45.
Moorhouse P, Rockwood K. Frailty and its quantitative clinical evaluation. The journal of the Royal College of Physicians of Edinburgh. 2012;42(4):333–340
Searle SD, Mitnitski A, Gahbauer EA, A standard procedure for creating a frailty index. BMC Geriatr. 2008;8:24.
Subramaniam S, Aalberg JJ, Soriano RP, et al. New 5-Factor Modified Frailty Index Using American College of Surgeons NSQIP Data. J Am Coll Surg. 2018 Feb;226(2):173-181.e8. doi: 10.1016/j.jamcollsurg .2017.11.005. Epub 2017 Nov 16. PMID: 29155268.
Guralnik JM, Simonsick EM, Ferrucci L, et al. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol. 1994;49(2):M85–94.
Soler V, Sourdet S, Balardy L, et al. Visual Impairment Screening at the Geriatric Frailty Clinic for Assessment of Frailty and Prevention of Disability at the Gérontopôle. J Nutr Health Aging. 2016;20(8):870–877
Mitnitski AB, Mogilner AJ, Rockwood K. Accumulation of deficits as a proxy measure of aging. Scientific World Journal. 2001;1:323–336.
Steverink N, Slaets J, Schuurmans H, et al. Measuring frailty: developing and testing of the Groningen frailty indicator (GFI) Gerontologist. 2001;41(1):236–237.
Peters LL, Boter H, Buskens E, et al.. Measurement properties of the Groningen frailty indicator in home-dwelling and institutionalized elderly people. J Am Med Dir Assoc. 2012;13(6):546–51.
Rolfson DB, Majumdar SR, Tsuyuki RT, Tahir A, Rockwood K. Validity and reliability of the Edmonton frail scale. Age Ageing. 2006;35(5):526–529.
Saliba D, Elliott M, Rubenstein LZ, et al. The vulnerable elders survey: a tool for identifying vulnerable older people in the community. J Am Geriatr Soc. 2001;49(12):1691–1699.
Stuck AE, Iliffe S. Comprehensive geriatric assessment for older adults. BMJ. 2011:343
Hoover M, Rotermann M, Sanmartin C, et al. Validation of an index to estimate the prevalence of frailty among community-dwelling seniors. Health Rep. 2013;24(9):10–17.
Gobbens RJ, Krans A, van Assen MA. Validation of an integral conceptual model of frailty in older residents of assisted living facilities. Arch Gerontol Geriatr. 2015;61(3):400–10.
Hebert R, Carrier R, Bilodeau A. The Functional Autonomy Measurement System (SMAF): description and validation of an instrument for the measurement of handicaps. Age Ageing. 1988;17(5):293–302.
Tocchi C, Dixon J, Naylor M, et al. Development of a frailty index measure for older adults: The Frailty Index for Elders. Journal of Nursing Measurement. 2014;22(2):223–240.
De Lepeleire J, Ylieff M, Stessens J, et al. The validity of the Frail instrument in general practice. Arch Public Health. 2004;62:185–196.
Lachs MS, Feinstein AR, Cooney LM, Jr, et al. A simple procedure for general screening for functional disability in elderly patients. Ann Intern Med. 1990;112(9):699–706.
Cacciatore F, Abete P, Mazzella F, et al. Frailty predicts long-ter mortality in elderly subjects with chronic heart failure. Eur J Clin Invest. 2005;35(12):723–730.
De Witte N, Gobbens R, De Donder L, et al. Validation of the comprehensive frailty assessment instrument against the Tilburg frailty indicator. Eur Geriatr Med. 2013;4:248–254.
Warnier RMJ, van Rossum E, van Leendert J, et al. Screening for frailty in older hospitalized patients: Reliability and feasibility of the Maastricht frailty screening tool for hospitalized patients (MFST-HP) Res Gerontol Nurs. 2016;9:243–251
Sewo Sampaio PY, Sampaio RAC, Yamada M, et al. Validation and Translation of the Kihon Checklist (frailty index) into Brazilian Portuguese. Geriatr Gerontol Int. 2013;14(3):561–569.
Kajsa E, Katarina W, Sten L, et al. Screening for frailty among older emergency department visitors: Validation of the new FRESH-screening instrument. BMC Emerg Med. 2016;16(1):27.
National Institute for Clinical Excellence. NICE, ed. London: 2016. Multimorbidity: clinical assessment and management, NICE guidelines NG56; p. 443.
Hippisley-Cox J, Coupland C. Development and validation of QMortality risk prediction algorithm to estimate short term risk of death and assess frailty: cohort study. BMJ. 2017;20:358. j4208.
Salaffi F, Di Carlo M, Farah S, et al Development and validation of a multidimensional frailty screening instrument in a cohort of patients with rheumatoid arthritis: the Comprehensive Rheumatologic Assessment of Frailty (CRAF) index. Clin Exp Rheumatol. 2019 (in press)
Salaffi F, De Angelis R, Grassi W MArche Pain Prevalence; INvestigation Group (MAPPING) study. Prevalence of musculoskeletal conditions in an Italian population sample: results of a regional community-based study. I. The MAPPING study. Clin Exp Rheumatol. 2005;23(6):819–28.
Cimmino MA, Salaffi F. The fate of the patient with musculoskeletal disorders in Italy: an epidemiological insight. Clin Exp Rheumatol. 2007;25(6):803–805.
Harris ED, Jr Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med. 1990;322:1277–1289.
Choi SJ, Rho YH, Ji JD, et al. Genome scan meta-analysis of rheumatoid arthritis. Rheumatology (Oxford) 2006;45:166–170.
Salaffi F, De Angelis R, Stancati A, et al Arche Pain; Prevalence INvestigation Group (MAPPING) study. Health-related quality of life in multiple musculoskeletal conditions: a cross-sectional population based epidemiological study. II. The MAPPING study. Clin Exp Rheumatol. 2005;23(6):829–39.
Salaffi F, Di Carlo M, Carotti M, et al. The impact of different rheumatic diseases on health-related quality of life: a comparison with a selected sample of healthy individuals using SF-36 questionnaire, EQ-5D and SF-6D utility values. Acta Biomed. 2019;89(4):541–557.
Hastings SN, Purser JL, Johnson KS, et al. Frailty predicts some but not all adverse outcomes in older adults discharged from the emergency department. J Am Geriatr Soc. 2008;56:1651–1657.
Salaffi F, Carotti M, Stancati A, et al. Health-related quality of life in older adults with symptomatic hip and knee osteoarthritis: a comparison with matched healthy controls. Aging Clin Exp Res. 2005;17(4):255–63.
Leardini G, Salaffi F, Caporali R, et al Italian Group for Study of the Costs of Arthritis. Direct and indirect costs of osteoarthritis of the knee. Clin Exp Rheumatol. 2004;22(6):699–706
Van Saase JLCM, van Romunde LKJ, Cats A, et al Epidemiology of osteoarthritis: Zoetermeer survey. Comparison of radiological osteoarthritis in a Dutch population with that in 10 other populations. Ann Rheum Dis. 1989;48:271–280.
Miguel Rde C, Dias RC, Dias JM, et al. Frailty syndrome in the community-dwelling elderly with osteoarthritis. Rev Bras Reumatol. 2012;52(3):331–47.
Misra D, Felson DT, Silliman RA, et al. Knee osteoarthritis and frailty: Findings from the multicenter osteoarthritis study and osteoarthritis initiative. J Gerontol A Biol Sci Med Sci. 2015;70(3):339–449.
Shega JW, Dale W, Andrew M, et al. Persistent pain and frailty: A case for homeostenosis. J Am Geriatr Soc. 2012;60(1):113–117.
Bindawas SM, Vennu V, Stubbs B. Longitudinal Relationship Between Knee Pain Status and Incident Frailty: Data from the Osteoarthritis Initiative. Pain Med. 2018 Nov 1;19(11):2146–2153.
Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European working group on sarcopenia in older people. Age Ageing. 2010;39(4):412–23.
Walston JD. Sarcopenia in older adults. Current opinion in rheumatology. 2012;24(6):623–7.
Verschueren S, Gielen E, O’Neill TW, et al. Sarcopenia and its relationship with bone mineral density in middleaged and elderly European men. Osteoporos Int. 2013;24:87–98.
Cooper C, Dere W, Evans W, et al. Frailty and sarcopenia: definitions and outcome parameters. Osteoporos. Int. 2012;23:1839–48.
Grimby G, Saltin B. The ageing muscle. Clinical Physiology. 1983;3:209–18. [PubMed] [Google Scholar]
Faulkner JA, Larkin LM, Claflin DR, Brooks SV. Age-Related Changes In The Structure And Function Of Skeletal Muscles. 2007:1091–6.
Liu LK, Lee WJ, Liu CL, et al. Age-related skeletal muscle mass loss and physical performance in Taiwan: implications to diagnostic strategy of sarcopenia in Asia. Geriatr Gerontol Int. 2013;13:964–971
Rockwood K, Bergman H. FRAILTY: a report from the 3(rd) Joint Workshop of IAGG/WHO/SFGG, Athens, Jan 2012. Can Geriatr J. 2012;15:31–36
Lipsitz LA. Dynamics of stability: the physiologic basis of functional health and frailty. J Gerontol A Biol Sci Med Sci. 2002;57:115–125.
Fried LP, Tangen C, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56A:M1–M11.
Sternberg SA, Levin R, Dkaidek S, Edelman S, Resnick T, Menczel J. Frailty and osteoporosis in older women a prospective study. Osteoporos Int. 2013 Sep 4; Epub.
Compston JE, McClung MR, Leslie WD. Osteoporosis. Lancet (London England) (2019) 393(10169):36476. 10.1016/s0140-6736(18)32112-3
Panula J, Pihlajamäki H, Mattila VM, et al. Mortality and cause of death in hip fracture patients aged 65 or older: a population-based study. BMC Musculoskelet Disord (2011) 12:105. 10.1186 /1471-2474-12-105
Cook MJ, Oldroyd A, Pye SR, et al. Frailty and bone health in European men. Age Ageing (2017) 46(4):635–41.10.1093 /ageing /afw
Kojima G. Frailty as a predictor of fractures among community-dwelling older people: A systematic review and meta-analysis. Bone (2016) 90:116–22. 10.1016/j.bone.2016.06.009
Li G, Papaioannou A, Thabane L, et al Frailty Change and Major Osteoporotic Fracture in the Elderly: Data from the Global Longitudinal Study of Osteoporosis in Women 3-Year Hamilton Cohort. J Bone Miner Res (2016) 31(4):718–24. 10.1002/jbmr.2739
Kanis JA, Cooper C, Rizzoli R, et al, on behalf of the Scientific Advisory Board of the European Society for C. Economic Aspects of O et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporosis Int (2019) 30(1):3–44. 10.1007/s00198-018-4704-5
Clegg A, Young J, Iliffe S, et al Frailty in elderly people. Lancet (2013) 381(9868):752–62. 10.1016/S0140-6736(12)62167-9 [
Johnston CB, Dagar M. Osteoporosis in Older Adults. Med Clinics North America (2020) 104(5):873.84. 10.1016/j.mcna.2020.06.004
Francesca Motta ,1, 2 Antonio Sica , 3, 4 ve Carlo Selmi 1, 2, * Frailty in Rheumatic Diseases Front Immunol. 2020; 11: 576134. Published online 2020 Oct 29. doi: 10.3389/fimmu.2020.576134
Tsokos GC.Systemic lupus erythematosus. N Engl J Med (2011) 365(22):2110–21.10.1056/NEJ Mra1100359
Lisnevskaia L, Murphy G, Isenberg D. Systemic lupus erythematosus. Lancet (London England) (2014) 384(9957):1878–88. 10.1016/s0140-6736(14)60128-8
Fanouriakis A, Kostopoulou M, Alunno A, et al. update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis (2019) 78(6):736–45. 10.1136/annrheumdis-2019-215089
Urowitz MB, Gladman DD, Tom BDM, et al. Changing patterns in mortality and disease outcomes for patients with systemic lupus erythematosus. J Rheumatol (2008) 35(11):2152–8. 10.3899/ jrheum. 080214
Katz PP, Andrews J, Yazdany J, et al. Is frailty a relevant concept in SLE? Lupus Sci Med (2017) 4(1):e000186–e. 10.1136/lupus-2016-000186
Denton CP, Khanna D. Systemic sclerosis. Lancet (London England) (2017) 390(10103):1685–99. 10.1016/s0140-6736(17)30933-9
Elhai M, Meune C, Avouac J, et al Trends in mortality in patients with systemic sclerosis over 40 years: a systematic review and meta-analysis of cohort studies. Rheumatol (Oxford) (2012) 51(6):1017–26. 10.1093/rheumatology/ker269
Kowal-Bielecka O, Fransen J, Avouac J, et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis (2017) 76(8):1327–39. 10.1136/annrheumdis-2016-209909
Fernández-Codina A, Walker KM, Pope JE, the Scleroderma Algorithm G Treatment Algorithms for Systemic Sclerosis According to Experts. Arthritis Rheumatol (2018) 70(11):1820–8. 10.1002/art.40560
Barnes H, Holland AE, Westall GP, et al. Cyclophosphamide for connective tissue disease-associated interstitial lung disease. Cochrane Database Syst Rev (2018) 1(1):CD010908–CD. 10.1002/14651858.CD010908.pub2
Searle SD, Mitnitski A, Gahbauer EA, Gill TM, Rockwood K. A standard procedure for creating a frailty index. BMC Geriatrics (2008) 8:24–. 10.1186/1471-2318-8-24
Rockwood MR, MacDonald E, Sutton E, et al Canadian Scleroderma Research G. Frailty index to measure health status in people with systemic sclerosis. J Rheumatol (2014) 41(4):698–705. 10.3899/jrheum.130182
Guler SA, Kwan JM, Winstone TA, et al. Severity and features of frailty in systemic sclerosis-associated interstitial lung disease. Respir Med (2017) 129:1,7.10.1016/j.rmed.2017.05. 012
Yates M, Watts R. ANCA-associated vasculitis. Clin Med (Lond) (2017) 17(1):60–4. 10.7861/clinmedicine. 17-1-60
Yates M, Watts RA, Bajema IM, et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis (2016) 75(9):1583–94. 0.1136/annrheumdis-2016-209133
Emejuaiwe N. Treatment Strategies in ANCA-Associated Vasculitis. Curr Rheumatol Rep (2019) 21(7):33. 10.1007/s11926-019-0835-8
Thomas K, Vassilopoulos D. Infections and vasculitis. Curr Opin Rheumatol (2017) 29(1):17–23. 10.1097/BOR.0000000000000348
Fried LP, Xue QL, Cappola AR, Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment. J Gerontol A Biol Sci Med Sci. 2009;64:1049–1057.
Leng S, Chaves P, Koenig K, et al Serum interleukin-6 and hemoglobin as physiological correlates in the geriatric syndrome of frailty: a pilot study. J Am Geriatr Soc. 2002;50:1268–1271.
Leng S, Fried LP. Inflammatory markers and frailty. In: Fulop T, Franceschi C, Hirokawa K, Pawelec G, editors. Handbook on Immunosenescence: Basic Understanding and Clinical Applications. New York: Springer; 2009. pp. 1293–1303.
Li HF, Manwani B, Leng S. Frailty, inflammation, and immunity. Aging Dis. 2001;2:466–473.
Leng S, Yang H, Walston J. Decreased cell proliferation and altered cytokine production in frail older adults. Aging Clin Exp Res. 2004;16:249–252
Collerton J, Martin-Ruiz C, Davies K, et al. Frailty and the role of inflammation, immunosenescence and cellular ageing in the very old: cross-sectional findings from the Newcastle 85+ Study. Mech Ageing Dev. 2012;133:456–466.
Hubbard RE, O’Mahony MS, Savva GM,. Inflammation and frailty measures in older people. J Cell Mol Med. 2009;13:3103–3109
Walston J, McBurnie MA, Newman A, et al. Frailty and activation of the inflammation and coagulation systems with and without clinical morbidities: results from the Cardiovascular Health Study. Arch Intern Med. 2002;162:2333–2341.
Leng SX, Tian X, Matteini A, et al. IL-6-independent association of elevated serum neopterin levels with prevalent frailty in community-dwelling older adults. Age Ageing. 2011;40:475–481.
Ramarathan R, Kohli A, Ingaramo MC, et al. Serum chitotriosidase, a putative marker of chronically activated macrophages, increases with normal aging. J Gerontol A Biol Sci Med Sci. 2013;68:1303–1309.
Leng SX, Xue QL, Tian J, et al. Inflammation and frailty in older women. J Am Geriatr Soc. 2007;55:864–871.
Leng SX, Xue QL, Tian J, et al Association of neutrophil and monocyte counts with frailty in community-dwelling older women: results from the Women’s Health and Aging Studies I. Exp Gerontol. 2009;44:511–516.
Qu T, Yang H, Walston JD, et al Upregulated monocytic expression of CXC chemokine ligand 10 (CXCL-10) and its relationship with serum interleukin-6 levels in the syndrome of frailty. Cytokine. 2009;46:319–324.
Visser M, Pahor M, Taaffe DR, et al. Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol A Biol Sci Med Sci. 2002;57:M326–M332.
Puts MT, Visser M, Twisk JW, et al. Endocrine and inflammatory markers as predictors of frailty. Clin Endocrinol (Oxf) 2005;63:403–411.
Chaves PH, Semba RD, Leng SX, et al. Impact of anemia and cardiovascular disease on frailty status of community-dwelling older women: the Women’s Health and Aging Studies I and II. J Gerontol A Biol Sci Med Sci. 2005;60:729–735.
Leng SX, Cappola AR, Andersen RE, et al. Serum levels of insulin-like growth factor-I (IGF-I) and dehydroepiandrosterone sulfate (DHEA-S), and their relationships with serum interleukin-6, in the geriatric syndrome of frailty. Aging Clin Exp Res. 2004;16:153–157.
Vasto S, Mocchegiani E, Malavolta M, et al. Zinc and inflammatory/immune response in aging. Ann N Y Acad Sci. 2007;1100:111–122.
LaCroix AZ, Gray SL, Aragaki A, et al. Statin use and incident frailty in women aged 65 years or older: prospective findings from the Women’s Health Initiative Observational Study. J Gerontol A Biol Sci Med Sci. 2008;63:369–375
Leng SX, Yang H, Walston JD. Decreased cell proliferation and altered cytokine production in frail older adults. Aging Clin Exp Res (2004) 16(3):249–52. 10.1007/bf03327392
Walston J, Fedarko N, Yang H, et al. The physical and biological characteriza tion of a frail mouse model. J Gerontol Ser A Biol Sci Med Sci (2008) 63(4):391–8. 10.1093/gerona /63.4.391
Qu T, Yang H, Walston JD,. Upregulated monocytic expression of CXC chemokine ligand 10 (CXCL-10) and its relationship with serum interleukin-6 levels in the syndrome of frailty. Cytokine (2009) 46(3):319–24. 10.1016/j.cyto.2009.02.015
Hubbard RE, O’Mahony MS, Savva GM, Inflammation and frailty measures in older people. J Cell Mol Med (2009) 13(9B):3103–9. 10.1111/j.1582-4934.2009.00733.x
Collerton J, Martin-Ruiz C, Davies K, et al. Frailty and the role of inflammation, immunosenescence and cellular ageing in the very old: cross-sectional findings from the Newcastle 85+ Study. Mech Ageing Dev (2012) 133(6):456–66. 10.1016/j.mad.2012.05.005
Leng SX, Tian X, Matteini A, et al. IL-6-independent association of elevated serum neopterin levels with prevalent frailty in community-dwelling older adults. Age Ageing (2011) 40(4):475–81. 10.1093/ageing/afr047
Schmaltz HN, Fried LP, Xue Q-L, et al. Chronic cytomegalovirus infection and inflammation are associated with prevalent frailty in community-dwelling older women. J Am Geriatrics Soc (2005) 53(5):747–54. 10.1111/j.1532-5415.2005.53250.x
Wang GC, Kao WHL, Murakami P, et al. Cytomegalovirus infection and the risk of mortality and frailty in older women: a prospective observational cohort study. Am J Epidemiol (2010) 171(10):1144–52. 10.1093/aje/kwq062
D. Kumar, K. Shankar, S. Patel, et al. Chronic hyperinsulinemia promotes meta-inflammation and extracellular matrix deposition in adipose tissue: Implications of nitric oxide Mol Cell Endocrinol.477 (2018), pp. 15-28
Mantovani A, Biswas SK, Galdiero MR, et al. Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol (2013) 229(2):176–85. 10.1002/path.4133
Novak ML, Koh TJ. Phenotypic Transitions of Macrophages Orchestrate Tissue Repair. Am J Pathol (2013) 183(5):1352–63. 10.1016/j.ajpath.2013.06.034
Sica A, Erreni M, Allavena P, et al. Macrophage polarization in pathology. Cell Mol Life Sci (2015) 72(21): 4111-26. 10.1007/s00018-015-1995-y
Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest (2012)122(3):78 7–95. 10.1172/jci59643
Pai S, Thomas R. Immune deficiency or hyperactivity-Nf-κb illuminates autoimmunity. J Autoimmun (2008) 31(3):245–51. 10.1016/j.jaut.2008.04.012
Takeuch O, Akira S. Epigenetic control of macrophage polarization. Eur J Immunol (2011) 41(9):2490–3. 10.1002/eji.201141792
Yoshino J, Mills Kathryn F, Yoon Myeong J. et al. Nicotinamide Mononucleotide, a Key NAD+ Intermediate, Treats the Pathophysiology of Diet- and Age-Induced Diabetes in Mice. Cell Metab (2011) 14(4): 528–36. 10.1016/j.cmet.2011.08.014
Salminen A, Kauppinen A, Kaarniranta K. AMPK/Snf1 signaling regulates histone acetylation: Impact on gene expression and epigenetic functions. Cell Signal (2016) 28(8):887–95. 10.1016/j.cellsig.2016.03.009
Ghosh D, Levault KR, Brewer GJ. Relative importance of redox buffers GSH and NAD(P)H in age-related neurodegeneration and Alzheimer disease-like mouse neurons. Aging Cell (2014) 13(4):631–40. 10.1111/acel.12216
Singh T, Newman AB. Inflammatory markers in population studies of aging. Ageing Res Rev (2011) 10(3): 319–29. 10.1016/j.arr.2010.11.002
Burgos ES, Vetticatt MJ, Schramm VL. Recycling Nicotinamide. The Transition-State Structure of Human Nicotinamide Phosphoribosyltransferase. J Am Chem Soc (2013) 135(9):3485–93. 10.1021/ja310180c
Ramakrishnan SK, Zhang H, Ma X, Jung I, Schwartz AJ, Triner D, et al. Intestinal non-canonical NFκB signaling shapes the local and systemic immune response. Nat Commun (2019) 10(1):660. 10.1038/s41467-019-08581-8
Netea MG, Joosten LAB, Latz E, et al. Trained immunity: A program of innate immune memory in health and disease. Science (2016) 352(6284):aaf1098.10.1126 /science .aaf1098
Ferrucci L, Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol (2018) 15(9):505–22. 10.1038/s41569-018-0064-2
Marzetti E, Calvani R, Tosato M, et al. Sarcopenia: an overview. Aging Clin Exp Res (2017) 29(1):11–7. 10.1007/s40520-016-0704-5
Liguori I, Russo G, Aran L, et al. Sarcopenia: assessment of disease burden and strategies to improve outcomes. Clin Interv Aging (2018) 13:913–27. 10.2147/cia.s149232
Clegg A, Hassan-Smith Z. Frailty and the endocrine system. Lancet Diabetes Endocrinol (2018) 6(9):743–52. 10.1016/s2213-8587(18)30110-4
Leng SX, Hung W, Cappola AR, et al. White blood cell counts, insulin-like growth factor-1 levels, and frailty in community-dwelling older women. J Gerontol A Biol Sci Med Sci. 2009;64:499–502.
Martín AI, Priego T, López-Calderón A. Hormones and Muscle Atrophy. In: Xiao J, editor. Muscle Atrophy. Singapore: Springer Singapore; (2018). p. 207–33
Shardell M, Hicks GE, Miller RR, et al. Association of low vitamin D levels with the frailty syndrome in men and women. J Gerontol A Biol Sci Med Sci. 2009;64:69–75.
Varadhan R, Walston J, Cappola AR. Higher levels and blunted diurnal variation of cortisol in frail older women. J Gerontol A Biol Sci Med Sci. 2008;63:190–195.
Skversky AL, Kumar J, Abramowitz M. et al. Association of Glucocorticoid Use and Low 25-Hydroxyvitamin D Levels: Results from the National Health and Nutrition Examination Survey (NHANES): 2001–2006. J Clin Endocrinol Metab (2011) 96(12):3838–45. 10.1210/jc.2011-1600
Tajar A, Lee DM, Pye SR, O’Connell MDL, Ravindrarajah R, Gielen E, et al. The association of frailty with serum 25-hydroxyvitamin D and parathyroid hormone levels in older European men. Age Ageing (2013) 42(3):352–9. 10.1093/ageing/afs162
Caprio M, Infante M, Calanchini M, et al. Vitamin D: not just the bone. Evidence for beneficial pleiotropic extraskeletal effects. Eat Weight Disord - Stud Anorexia Bulimia Obes (2017) 22(1):27–41. 10.1007/s40519-016-0312-6
Yin K, Agrawal DK, Vitamin D. and inflammatory diseases. J Inflammation Res (2014) 7:69–87. 10.2147 /jir.s63898
Fabbri A, Infante M, Ricordi C. Vitamin D status: a key modulator of innate immunity and natural defense from acute viral respiratory infections. Eur Rev Med Pharmacol Sci (2020) 24(7):4048–52. 10. 26355/ eurrev_202004_20876
Song X, Mitnitski A, Rockwood K. Nontraditional risk factors combine to predict Alzheimer disease and dementia. Neurology (2011) 77(3):227–34. 10.1212/WNL.0b013e318225c6bc
Boyle PA, Buchman AS, Wilson RS, et al. Physical frailty is associated with incident mild cognitive impairment in community-based older persons. J Am Geriatrics Soc (2010) 58(2):248–55. 10.1111/j.1532-5415.2009.02671.x
Soysal P, Veronese N, Thompson T. et al. Relationship between depression and frailty in older adults: A systematic review and meta-analysis. Ageing Res Rev (2017) 36:78–87. 10.1016/j.arr.2017.03.005
Collard RM, Arts MHL, Schene AH, et al. The impact of frailty on depressive disorder in later life: Findings from the Netherlands Study of depression in older persons. Eur Psychiatry (2017) 43:66–72. 10.1016/j.eurpsy.2017.01.003
Chang H-Y, Fang H-L, Ting T-T, et al. The Co-Occurrence Of Frailty (Accumulation Of Functional Deficits) And Depressive Symptoms, And Its Effect On Mortality In Older Adults: A Longitudinal Study. Clin Interv Aging (2019) 14:1671–80. 10.2147/cia.s210072
Theou O, Stathokostas L, Roland KP, et al. The effectiveness of exercise interventions for the management of frailty: a systematic review. J Aging Res. 2011;2011:569194. [PMC free article] [PubMed] [Google Scholar]
Forster A, Lambley R, Hardy J, et al. Rehabilitation for older people in long-term care. Cochrane Database Syst Rev. 2009;(1):CD004294.
Clegg AP, Barber SE, Young JB, et al. Do home-based exercise interventions improve outcomes for frail older people? Findings from a systemic review. Rev Clin Gerontol. 2012;22:68–78. [PMC free article] [PubMed] [Google Scholar]
Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363:109–122.
Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288:321–333.
Friedlander AL, Butterfield GE, Moynihan S, et al. One year of insulin-like growth factor I treatment does not affect bone density, body composition, or psychological measures in postmenopausal women. J Clin Endocrinol Metab. 2001;86:1496–1503.
Campbell S, Szoeke C. Pharmacological treatment of frailty in the elderly. J Pharm Pract Res2009;39:147–151.
Referanslar
Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–M56
Walston J, Hadley EC, Ferrucci L, et al. Research agenda for frailty in older adults: toward a better understanding of physiology and etiology: summary from the American geriatrics society/national institute on aging research conference on frailty in older adults. J Am Geriatr Soc. 2006;54:991–1001.
Rockwood K, Mitnitski A. Frailty defined by deficit accumulation and geriatric medicine defined by frailty. Clin Geriatr Med. 2011;27:17–2614.
Choi J, Ahn A, Kim S, Global prevalence of physical frailty by Fried’s criteria in community-dwelling elderly with national population based surveys. J Am Med Dir Assoc. 2015;16(7):548–50.
Michel JP, Cruz-Jentoft AJ, Cederholm T. Frailty, exercise and nutrition. Clin Geriatr Med. 2015;31(3):375.87
Alvarado BE, Zunzunegui MV, Beland F,. Life course social and health conditions linked to frailty in Latin American older men and women. J Gerontol A Biol Sci Med Sci. 2008;63(12):1399–406.
Shinkai S, Yoshida H, Taniguchi Y, et al. Public health approach to preventing frailty in the community and its effect on healthy aging in Japan. Geriatr Gerontol Int. 2016;(16 Suppl 1):87–97.
Collard RM, Boter H, Schoevers RA, Prevalence of frailty in community-dwelling older persons: a systematic review. J Am Geriatr Soc. 2012;60(8):1487–1492.
Mulasso A, Roppolo M, Giannotta F, Associations of frailty and psychosocial factors with autonomy in daily activities: a cross-sectional study in Italian community-dwelling older adults. Clin Interv Aging.2016;11(11):37,45
Wick JY. Understanding frailty in the geriatric population. Consult Pharm. 2011;26(9):634–45.
Moorhouse P, Rockwood K. Frailty and its quantitative clinical evaluation. The journal of the Royal College of Physicians of Edinburgh. 2012;42(4):333–340
Searle SD, Mitnitski A, Gahbauer EA, A standard procedure for creating a frailty index. BMC Geriatr. 2008;8:24.
Subramaniam S, Aalberg JJ, Soriano RP, et al. New 5-Factor Modified Frailty Index Using American College of Surgeons NSQIP Data. J Am Coll Surg. 2018 Feb;226(2):173-181.e8. doi: 10.1016/j.jamcollsurg .2017.11.005. Epub 2017 Nov 16. PMID: 29155268.
Guralnik JM, Simonsick EM, Ferrucci L, et al. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol. 1994;49(2):M85–94.
Soler V, Sourdet S, Balardy L, et al. Visual Impairment Screening at the Geriatric Frailty Clinic for Assessment of Frailty and Prevention of Disability at the Gérontopôle. J Nutr Health Aging. 2016;20(8):870–877
Mitnitski AB, Mogilner AJ, Rockwood K. Accumulation of deficits as a proxy measure of aging. Scientific World Journal. 2001;1:323–336.
Steverink N, Slaets J, Schuurmans H, et al. Measuring frailty: developing and testing of the Groningen frailty indicator (GFI) Gerontologist. 2001;41(1):236–237.
Peters LL, Boter H, Buskens E, et al.. Measurement properties of the Groningen frailty indicator in home-dwelling and institutionalized elderly people. J Am Med Dir Assoc. 2012;13(6):546–51.
Rolfson DB, Majumdar SR, Tsuyuki RT, Tahir A, Rockwood K. Validity and reliability of the Edmonton frail scale. Age Ageing. 2006;35(5):526–529.
Saliba D, Elliott M, Rubenstein LZ, et al. The vulnerable elders survey: a tool for identifying vulnerable older people in the community. J Am Geriatr Soc. 2001;49(12):1691–1699.
Stuck AE, Iliffe S. Comprehensive geriatric assessment for older adults. BMJ. 2011:343
Hoover M, Rotermann M, Sanmartin C, et al. Validation of an index to estimate the prevalence of frailty among community-dwelling seniors. Health Rep. 2013;24(9):10–17.
Gobbens RJ, Krans A, van Assen MA. Validation of an integral conceptual model of frailty in older residents of assisted living facilities. Arch Gerontol Geriatr. 2015;61(3):400–10.
Hebert R, Carrier R, Bilodeau A. The Functional Autonomy Measurement System (SMAF): description and validation of an instrument for the measurement of handicaps. Age Ageing. 1988;17(5):293–302.
Tocchi C, Dixon J, Naylor M, et al. Development of a frailty index measure for older adults: The Frailty Index for Elders. Journal of Nursing Measurement. 2014;22(2):223–240.
De Lepeleire J, Ylieff M, Stessens J, et al. The validity of the Frail instrument in general practice. Arch Public Health. 2004;62:185–196.
Lachs MS, Feinstein AR, Cooney LM, Jr, et al. A simple procedure for general screening for functional disability in elderly patients. Ann Intern Med. 1990;112(9):699–706.
Cacciatore F, Abete P, Mazzella F, et al. Frailty predicts long-ter mortality in elderly subjects with chronic heart failure. Eur J Clin Invest. 2005;35(12):723–730.
De Witte N, Gobbens R, De Donder L, et al. Validation of the comprehensive frailty assessment instrument against the Tilburg frailty indicator. Eur Geriatr Med. 2013;4:248–254.
Warnier RMJ, van Rossum E, van Leendert J, et al. Screening for frailty in older hospitalized patients: Reliability and feasibility of the Maastricht frailty screening tool for hospitalized patients (MFST-HP) Res Gerontol Nurs. 2016;9:243–251
Sewo Sampaio PY, Sampaio RAC, Yamada M, et al. Validation and Translation of the Kihon Checklist (frailty index) into Brazilian Portuguese. Geriatr Gerontol Int. 2013;14(3):561–569.
Kajsa E, Katarina W, Sten L, et al. Screening for frailty among older emergency department visitors: Validation of the new FRESH-screening instrument. BMC Emerg Med. 2016;16(1):27.
National Institute for Clinical Excellence. NICE, ed. London: 2016. Multimorbidity: clinical assessment and management, NICE guidelines NG56; p. 443.
Hippisley-Cox J, Coupland C. Development and validation of QMortality risk prediction algorithm to estimate short term risk of death and assess frailty: cohort study. BMJ. 2017;20:358. j4208.
Salaffi F, Di Carlo M, Farah S, et al Development and validation of a multidimensional frailty screening instrument in a cohort of patients with rheumatoid arthritis: the Comprehensive Rheumatologic Assessment of Frailty (CRAF) index. Clin Exp Rheumatol. 2019 (in press)
Salaffi F, De Angelis R, Grassi W MArche Pain Prevalence; INvestigation Group (MAPPING) study. Prevalence of musculoskeletal conditions in an Italian population sample: results of a regional community-based study. I. The MAPPING study. Clin Exp Rheumatol. 2005;23(6):819–28.
Cimmino MA, Salaffi F. The fate of the patient with musculoskeletal disorders in Italy: an epidemiological insight. Clin Exp Rheumatol. 2007;25(6):803–805.
Harris ED, Jr Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med. 1990;322:1277–1289.
Choi SJ, Rho YH, Ji JD, et al. Genome scan meta-analysis of rheumatoid arthritis. Rheumatology (Oxford) 2006;45:166–170.
Salaffi F, De Angelis R, Stancati A, et al Arche Pain; Prevalence INvestigation Group (MAPPING) study. Health-related quality of life in multiple musculoskeletal conditions: a cross-sectional population based epidemiological study. II. The MAPPING study. Clin Exp Rheumatol. 2005;23(6):829–39.
Salaffi F, Di Carlo M, Carotti M, et al. The impact of different rheumatic diseases on health-related quality of life: a comparison with a selected sample of healthy individuals using SF-36 questionnaire, EQ-5D and SF-6D utility values. Acta Biomed. 2019;89(4):541–557.
Hastings SN, Purser JL, Johnson KS, et al. Frailty predicts some but not all adverse outcomes in older adults discharged from the emergency department. J Am Geriatr Soc. 2008;56:1651–1657.
Salaffi F, Carotti M, Stancati A, et al. Health-related quality of life in older adults with symptomatic hip and knee osteoarthritis: a comparison with matched healthy controls. Aging Clin Exp Res. 2005;17(4):255–63.
Leardini G, Salaffi F, Caporali R, et al Italian Group for Study of the Costs of Arthritis. Direct and indirect costs of osteoarthritis of the knee. Clin Exp Rheumatol. 2004;22(6):699–706
Van Saase JLCM, van Romunde LKJ, Cats A, et al Epidemiology of osteoarthritis: Zoetermeer survey. Comparison of radiological osteoarthritis in a Dutch population with that in 10 other populations. Ann Rheum Dis. 1989;48:271–280.
Miguel Rde C, Dias RC, Dias JM, et al. Frailty syndrome in the community-dwelling elderly with osteoarthritis. Rev Bras Reumatol. 2012;52(3):331–47.
Misra D, Felson DT, Silliman RA, et al. Knee osteoarthritis and frailty: Findings from the multicenter osteoarthritis study and osteoarthritis initiative. J Gerontol A Biol Sci Med Sci. 2015;70(3):339–449.
Shega JW, Dale W, Andrew M, et al. Persistent pain and frailty: A case for homeostenosis. J Am Geriatr Soc. 2012;60(1):113–117.
Bindawas SM, Vennu V, Stubbs B. Longitudinal Relationship Between Knee Pain Status and Incident Frailty: Data from the Osteoarthritis Initiative. Pain Med. 2018 Nov 1;19(11):2146–2153.
Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European working group on sarcopenia in older people. Age Ageing. 2010;39(4):412–23.
Walston JD. Sarcopenia in older adults. Current opinion in rheumatology. 2012;24(6):623–7.
Verschueren S, Gielen E, O’Neill TW, et al. Sarcopenia and its relationship with bone mineral density in middleaged and elderly European men. Osteoporos Int. 2013;24:87–98.
Cooper C, Dere W, Evans W, et al. Frailty and sarcopenia: definitions and outcome parameters. Osteoporos. Int. 2012;23:1839–48.
Grimby G, Saltin B. The ageing muscle. Clinical Physiology. 1983;3:209–18. [PubMed] [Google Scholar]
Faulkner JA, Larkin LM, Claflin DR, Brooks SV. Age-Related Changes In The Structure And Function Of Skeletal Muscles. 2007:1091–6.
Liu LK, Lee WJ, Liu CL, et al. Age-related skeletal muscle mass loss and physical performance in Taiwan: implications to diagnostic strategy of sarcopenia in Asia. Geriatr Gerontol Int. 2013;13:964–971
Rockwood K, Bergman H. FRAILTY: a report from the 3(rd) Joint Workshop of IAGG/WHO/SFGG, Athens, Jan 2012. Can Geriatr J. 2012;15:31–36
Lipsitz LA. Dynamics of stability: the physiologic basis of functional health and frailty. J Gerontol A Biol Sci Med Sci. 2002;57:115–125.
Fried LP, Tangen C, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56A:M1–M11.
Sternberg SA, Levin R, Dkaidek S, Edelman S, Resnick T, Menczel J. Frailty and osteoporosis in older women a prospective study. Osteoporos Int. 2013 Sep 4; Epub.
Compston JE, McClung MR, Leslie WD. Osteoporosis. Lancet (London England) (2019) 393(10169):36476. 10.1016/s0140-6736(18)32112-3
Panula J, Pihlajamäki H, Mattila VM, et al. Mortality and cause of death in hip fracture patients aged 65 or older: a population-based study. BMC Musculoskelet Disord (2011) 12:105. 10.1186 /1471-2474-12-105
Cook MJ, Oldroyd A, Pye SR, et al. Frailty and bone health in European men. Age Ageing (2017) 46(4):635–41.10.1093 /ageing /afw
Kojima G. Frailty as a predictor of fractures among community-dwelling older people: A systematic review and meta-analysis. Bone (2016) 90:116–22. 10.1016/j.bone.2016.06.009
Li G, Papaioannou A, Thabane L, et al Frailty Change and Major Osteoporotic Fracture in the Elderly: Data from the Global Longitudinal Study of Osteoporosis in Women 3-Year Hamilton Cohort. J Bone Miner Res (2016) 31(4):718–24. 10.1002/jbmr.2739
Kanis JA, Cooper C, Rizzoli R, et al, on behalf of the Scientific Advisory Board of the European Society for C. Economic Aspects of O et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporosis Int (2019) 30(1):3–44. 10.1007/s00198-018-4704-5
Clegg A, Young J, Iliffe S, et al Frailty in elderly people. Lancet (2013) 381(9868):752–62. 10.1016/S0140-6736(12)62167-9 [
Johnston CB, Dagar M. Osteoporosis in Older Adults. Med Clinics North America (2020) 104(5):873.84. 10.1016/j.mcna.2020.06.004
Francesca Motta ,1, 2 Antonio Sica , 3, 4 ve Carlo Selmi 1, 2, * Frailty in Rheumatic Diseases Front Immunol. 2020; 11: 576134. Published online 2020 Oct 29. doi: 10.3389/fimmu.2020.576134
Tsokos GC.Systemic lupus erythematosus. N Engl J Med (2011) 365(22):2110–21.10.1056/NEJ Mra1100359
Lisnevskaia L, Murphy G, Isenberg D. Systemic lupus erythematosus. Lancet (London England) (2014) 384(9957):1878–88. 10.1016/s0140-6736(14)60128-8
Fanouriakis A, Kostopoulou M, Alunno A, et al. update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis (2019) 78(6):736–45. 10.1136/annrheumdis-2019-215089
Urowitz MB, Gladman DD, Tom BDM, et al. Changing patterns in mortality and disease outcomes for patients with systemic lupus erythematosus. J Rheumatol (2008) 35(11):2152–8. 10.3899/ jrheum. 080214
Katz PP, Andrews J, Yazdany J, et al. Is frailty a relevant concept in SLE? Lupus Sci Med (2017) 4(1):e000186–e. 10.1136/lupus-2016-000186
Denton CP, Khanna D. Systemic sclerosis. Lancet (London England) (2017) 390(10103):1685–99. 10.1016/s0140-6736(17)30933-9
Elhai M, Meune C, Avouac J, et al Trends in mortality in patients with systemic sclerosis over 40 years: a systematic review and meta-analysis of cohort studies. Rheumatol (Oxford) (2012) 51(6):1017–26. 10.1093/rheumatology/ker269
Kowal-Bielecka O, Fransen J, Avouac J, et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis (2017) 76(8):1327–39. 10.1136/annrheumdis-2016-209909
Fernández-Codina A, Walker KM, Pope JE, the Scleroderma Algorithm G Treatment Algorithms for Systemic Sclerosis According to Experts. Arthritis Rheumatol (2018) 70(11):1820–8. 10.1002/art.40560
Barnes H, Holland AE, Westall GP, et al. Cyclophosphamide for connective tissue disease-associated interstitial lung disease. Cochrane Database Syst Rev (2018) 1(1):CD010908–CD. 10.1002/14651858.CD010908.pub2
Searle SD, Mitnitski A, Gahbauer EA, Gill TM, Rockwood K. A standard procedure for creating a frailty index. BMC Geriatrics (2008) 8:24–. 10.1186/1471-2318-8-24
Rockwood MR, MacDonald E, Sutton E, et al Canadian Scleroderma Research G. Frailty index to measure health status in people with systemic sclerosis. J Rheumatol (2014) 41(4):698–705. 10.3899/jrheum.130182
Guler SA, Kwan JM, Winstone TA, et al. Severity and features of frailty in systemic sclerosis-associated interstitial lung disease. Respir Med (2017) 129:1,7.10.1016/j.rmed.2017.05. 012
Yates M, Watts R. ANCA-associated vasculitis. Clin Med (Lond) (2017) 17(1):60–4. 10.7861/clinmedicine. 17-1-60
Yates M, Watts RA, Bajema IM, et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis (2016) 75(9):1583–94. 0.1136/annrheumdis-2016-209133
Emejuaiwe N. Treatment Strategies in ANCA-Associated Vasculitis. Curr Rheumatol Rep (2019) 21(7):33. 10.1007/s11926-019-0835-8
Thomas K, Vassilopoulos D. Infections and vasculitis. Curr Opin Rheumatol (2017) 29(1):17–23. 10.1097/BOR.0000000000000348
Fried LP, Xue QL, Cappola AR, Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment. J Gerontol A Biol Sci Med Sci. 2009;64:1049–1057.
Leng S, Chaves P, Koenig K, et al Serum interleukin-6 and hemoglobin as physiological correlates in the geriatric syndrome of frailty: a pilot study. J Am Geriatr Soc. 2002;50:1268–1271.
Leng S, Fried LP. Inflammatory markers and frailty. In: Fulop T, Franceschi C, Hirokawa K, Pawelec G, editors. Handbook on Immunosenescence: Basic Understanding and Clinical Applications. New York: Springer; 2009. pp. 1293–1303.
Li HF, Manwani B, Leng S. Frailty, inflammation, and immunity. Aging Dis. 2001;2:466–473.
Leng S, Yang H, Walston J. Decreased cell proliferation and altered cytokine production in frail older adults. Aging Clin Exp Res. 2004;16:249–252
Collerton J, Martin-Ruiz C, Davies K, et al. Frailty and the role of inflammation, immunosenescence and cellular ageing in the very old: cross-sectional findings from the Newcastle 85+ Study. Mech Ageing Dev. 2012;133:456–466.
Hubbard RE, O’Mahony MS, Savva GM,. Inflammation and frailty measures in older people. J Cell Mol Med. 2009;13:3103–3109
Walston J, McBurnie MA, Newman A, et al. Frailty and activation of the inflammation and coagulation systems with and without clinical morbidities: results from the Cardiovascular Health Study. Arch Intern Med. 2002;162:2333–2341.
Leng SX, Tian X, Matteini A, et al. IL-6-independent association of elevated serum neopterin levels with prevalent frailty in community-dwelling older adults. Age Ageing. 2011;40:475–481.
Ramarathan R, Kohli A, Ingaramo MC, et al. Serum chitotriosidase, a putative marker of chronically activated macrophages, increases with normal aging. J Gerontol A Biol Sci Med Sci. 2013;68:1303–1309.
Leng SX, Xue QL, Tian J, et al. Inflammation and frailty in older women. J Am Geriatr Soc. 2007;55:864–871.
Leng SX, Xue QL, Tian J, et al Association of neutrophil and monocyte counts with frailty in community-dwelling older women: results from the Women’s Health and Aging Studies I. Exp Gerontol. 2009;44:511–516.
Qu T, Yang H, Walston JD, et al Upregulated monocytic expression of CXC chemokine ligand 10 (CXCL-10) and its relationship with serum interleukin-6 levels in the syndrome of frailty. Cytokine. 2009;46:319–324.
Visser M, Pahor M, Taaffe DR, et al. Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol A Biol Sci Med Sci. 2002;57:M326–M332.
Puts MT, Visser M, Twisk JW, et al. Endocrine and inflammatory markers as predictors of frailty. Clin Endocrinol (Oxf) 2005;63:403–411.
Chaves PH, Semba RD, Leng SX, et al. Impact of anemia and cardiovascular disease on frailty status of community-dwelling older women: the Women’s Health and Aging Studies I and II. J Gerontol A Biol Sci Med Sci. 2005;60:729–735.
Leng SX, Cappola AR, Andersen RE, et al. Serum levels of insulin-like growth factor-I (IGF-I) and dehydroepiandrosterone sulfate (DHEA-S), and their relationships with serum interleukin-6, in the geriatric syndrome of frailty. Aging Clin Exp Res. 2004;16:153–157.
Vasto S, Mocchegiani E, Malavolta M, et al. Zinc and inflammatory/immune response in aging. Ann N Y Acad Sci. 2007;1100:111–122.
LaCroix AZ, Gray SL, Aragaki A, et al. Statin use and incident frailty in women aged 65 years or older: prospective findings from the Women’s Health Initiative Observational Study. J Gerontol A Biol Sci Med Sci. 2008;63:369–375
Leng SX, Yang H, Walston JD. Decreased cell proliferation and altered cytokine production in frail older adults. Aging Clin Exp Res (2004) 16(3):249–52. 10.1007/bf03327392
Walston J, Fedarko N, Yang H, et al. The physical and biological characteriza tion of a frail mouse model. J Gerontol Ser A Biol Sci Med Sci (2008) 63(4):391–8. 10.1093/gerona /63.4.391
Qu T, Yang H, Walston JD,. Upregulated monocytic expression of CXC chemokine ligand 10 (CXCL-10) and its relationship with serum interleukin-6 levels in the syndrome of frailty. Cytokine (2009) 46(3):319–24. 10.1016/j.cyto.2009.02.015
Hubbard RE, O’Mahony MS, Savva GM, Inflammation and frailty measures in older people. J Cell Mol Med (2009) 13(9B):3103–9. 10.1111/j.1582-4934.2009.00733.x
Collerton J, Martin-Ruiz C, Davies K, et al. Frailty and the role of inflammation, immunosenescence and cellular ageing in the very old: cross-sectional findings from the Newcastle 85+ Study. Mech Ageing Dev (2012) 133(6):456–66. 10.1016/j.mad.2012.05.005
Leng SX, Tian X, Matteini A, et al. IL-6-independent association of elevated serum neopterin levels with prevalent frailty in community-dwelling older adults. Age Ageing (2011) 40(4):475–81. 10.1093/ageing/afr047
Schmaltz HN, Fried LP, Xue Q-L, et al. Chronic cytomegalovirus infection and inflammation are associated with prevalent frailty in community-dwelling older women. J Am Geriatrics Soc (2005) 53(5):747–54. 10.1111/j.1532-5415.2005.53250.x
Wang GC, Kao WHL, Murakami P, et al. Cytomegalovirus infection and the risk of mortality and frailty in older women: a prospective observational cohort study. Am J Epidemiol (2010) 171(10):1144–52. 10.1093/aje/kwq062
D. Kumar, K. Shankar, S. Patel, et al. Chronic hyperinsulinemia promotes meta-inflammation and extracellular matrix deposition in adipose tissue: Implications of nitric oxide Mol Cell Endocrinol.477 (2018), pp. 15-28
Mantovani A, Biswas SK, Galdiero MR, et al. Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol (2013) 229(2):176–85. 10.1002/path.4133
Novak ML, Koh TJ. Phenotypic Transitions of Macrophages Orchestrate Tissue Repair. Am J Pathol (2013) 183(5):1352–63. 10.1016/j.ajpath.2013.06.034
Sica A, Erreni M, Allavena P, et al. Macrophage polarization in pathology. Cell Mol Life Sci (2015) 72(21): 4111-26. 10.1007/s00018-015-1995-y
Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest (2012)122(3):78 7–95. 10.1172/jci59643
Pai S, Thomas R. Immune deficiency or hyperactivity-Nf-κb illuminates autoimmunity. J Autoimmun (2008) 31(3):245–51. 10.1016/j.jaut.2008.04.012
Takeuch O, Akira S. Epigenetic control of macrophage polarization. Eur J Immunol (2011) 41(9):2490–3. 10.1002/eji.201141792
Yoshino J, Mills Kathryn F, Yoon Myeong J. et al. Nicotinamide Mononucleotide, a Key NAD+ Intermediate, Treats the Pathophysiology of Diet- and Age-Induced Diabetes in Mice. Cell Metab (2011) 14(4): 528–36. 10.1016/j.cmet.2011.08.014
Salminen A, Kauppinen A, Kaarniranta K. AMPK/Snf1 signaling regulates histone acetylation: Impact on gene expression and epigenetic functions. Cell Signal (2016) 28(8):887–95. 10.1016/j.cellsig.2016.03.009
Ghosh D, Levault KR, Brewer GJ. Relative importance of redox buffers GSH and NAD(P)H in age-related neurodegeneration and Alzheimer disease-like mouse neurons. Aging Cell (2014) 13(4):631–40. 10.1111/acel.12216
Singh T, Newman AB. Inflammatory markers in population studies of aging. Ageing Res Rev (2011) 10(3): 319–29. 10.1016/j.arr.2010.11.002
Burgos ES, Vetticatt MJ, Schramm VL. Recycling Nicotinamide. The Transition-State Structure of Human Nicotinamide Phosphoribosyltransferase. J Am Chem Soc (2013) 135(9):3485–93. 10.1021/ja310180c
Ramakrishnan SK, Zhang H, Ma X, Jung I, Schwartz AJ, Triner D, et al. Intestinal non-canonical NFκB signaling shapes the local and systemic immune response. Nat Commun (2019) 10(1):660. 10.1038/s41467-019-08581-8
Netea MG, Joosten LAB, Latz E, et al. Trained immunity: A program of innate immune memory in health and disease. Science (2016) 352(6284):aaf1098.10.1126 /science .aaf1098
Ferrucci L, Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol (2018) 15(9):505–22. 10.1038/s41569-018-0064-2
Marzetti E, Calvani R, Tosato M, et al. Sarcopenia: an overview. Aging Clin Exp Res (2017) 29(1):11–7. 10.1007/s40520-016-0704-5
Liguori I, Russo G, Aran L, et al. Sarcopenia: assessment of disease burden and strategies to improve outcomes. Clin Interv Aging (2018) 13:913–27. 10.2147/cia.s149232
Clegg A, Hassan-Smith Z. Frailty and the endocrine system. Lancet Diabetes Endocrinol (2018) 6(9):743–52. 10.1016/s2213-8587(18)30110-4
Leng SX, Hung W, Cappola AR, et al. White blood cell counts, insulin-like growth factor-1 levels, and frailty in community-dwelling older women. J Gerontol A Biol Sci Med Sci. 2009;64:499–502.
Martín AI, Priego T, López-Calderón A. Hormones and Muscle Atrophy. In: Xiao J, editor. Muscle Atrophy. Singapore: Springer Singapore; (2018). p. 207–33
Shardell M, Hicks GE, Miller RR, et al. Association of low vitamin D levels with the frailty syndrome in men and women. J Gerontol A Biol Sci Med Sci. 2009;64:69–75.
Varadhan R, Walston J, Cappola AR. Higher levels and blunted diurnal variation of cortisol in frail older women. J Gerontol A Biol Sci Med Sci. 2008;63:190–195.
Skversky AL, Kumar J, Abramowitz M. et al. Association of Glucocorticoid Use and Low 25-Hydroxyvitamin D Levels: Results from the National Health and Nutrition Examination Survey (NHANES): 2001–2006. J Clin Endocrinol Metab (2011) 96(12):3838–45. 10.1210/jc.2011-1600
Tajar A, Lee DM, Pye SR, O’Connell MDL, Ravindrarajah R, Gielen E, et al. The association of frailty with serum 25-hydroxyvitamin D and parathyroid hormone levels in older European men. Age Ageing (2013) 42(3):352–9. 10.1093/ageing/afs162
Caprio M, Infante M, Calanchini M, et al. Vitamin D: not just the bone. Evidence for beneficial pleiotropic extraskeletal effects. Eat Weight Disord - Stud Anorexia Bulimia Obes (2017) 22(1):27–41. 10.1007/s40519-016-0312-6
Yin K, Agrawal DK, Vitamin D. and inflammatory diseases. J Inflammation Res (2014) 7:69–87. 10.2147 /jir.s63898
Fabbri A, Infante M, Ricordi C. Vitamin D status: a key modulator of innate immunity and natural defense from acute viral respiratory infections. Eur Rev Med Pharmacol Sci (2020) 24(7):4048–52. 10. 26355/ eurrev_202004_20876
Song X, Mitnitski A, Rockwood K. Nontraditional risk factors combine to predict Alzheimer disease and dementia. Neurology (2011) 77(3):227–34. 10.1212/WNL.0b013e318225c6bc
Boyle PA, Buchman AS, Wilson RS, et al. Physical frailty is associated with incident mild cognitive impairment in community-based older persons. J Am Geriatrics Soc (2010) 58(2):248–55. 10.1111/j.1532-5415.2009.02671.x
Soysal P, Veronese N, Thompson T. et al. Relationship between depression and frailty in older adults: A systematic review and meta-analysis. Ageing Res Rev (2017) 36:78–87. 10.1016/j.arr.2017.03.005
Collard RM, Arts MHL, Schene AH, et al. The impact of frailty on depressive disorder in later life: Findings from the Netherlands Study of depression in older persons. Eur Psychiatry (2017) 43:66–72. 10.1016/j.eurpsy.2017.01.003
Chang H-Y, Fang H-L, Ting T-T, et al. The Co-Occurrence Of Frailty (Accumulation Of Functional Deficits) And Depressive Symptoms, And Its Effect On Mortality In Older Adults: A Longitudinal Study. Clin Interv Aging (2019) 14:1671–80. 10.2147/cia.s210072
Theou O, Stathokostas L, Roland KP, et al. The effectiveness of exercise interventions for the management of frailty: a systematic review. J Aging Res. 2011;2011:569194. [PMC free article] [PubMed] [Google Scholar]
Forster A, Lambley R, Hardy J, et al. Rehabilitation for older people in long-term care. Cochrane Database Syst Rev. 2009;(1):CD004294.
Clegg AP, Barber SE, Young JB, et al. Do home-based exercise interventions improve outcomes for frail older people? Findings from a systemic review. Rev Clin Gerontol. 2012;22:68–78. [PMC free article] [PubMed] [Google Scholar]
Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363:109–122.
Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288:321–333.
Friedlander AL, Butterfield GE, Moynihan S, et al. One year of insulin-like growth factor I treatment does not affect bone density, body composition, or psychological measures in postmenopausal women. J Clin Endocrinol Metab. 2001;86:1496–1503.
Campbell S, Szoeke C. Pharmacological treatment of frailty in the elderly. J Pharm Pract Res2009;39:147–151.
