Bone, Год журнала: 2022, Номер 164, С. 116539 - 116539
Опубликована: Авг. 23, 2022
Язык: Английский
Nature Reviews Cardiology, Год журнала: 2018, Номер 15(9), С. 505 - 522
Опубликована: Июль 31, 2018
Язык: Английский
Процитировано
2528
Hepatology, Год журнала: 2021, Номер 74(3), С. 1611 - 1644
Опубликована: Июль 7, 2021
Supported by the American Association for Study of Liver Diseases. Dr. Lai is partially supported R01 AG059183 and R21 AG067554. Srinivasan Dasarathy NIH RO1 GM119174; DK113196; P50 AA024333; AA021890; 3U01AA026976 ‐ 03S1; UO1 AA 026976; R56HL141744;UO1 DK061732; 5U01 DK062470‐17S2. Potential conflict interest: received grants from Axcella Lipocine. Bernal advises Versantis. Purpose Scope This Practice Guidance first Diseases (AASLD) practice guidance on management malnutrition, frailty, sarcopenia in patients with cirrhosis. represents consensus a panel experts after thorough review vigorous debate literature published to date, incorporating clinical experience common sense fill gaps when appropriate. Our goal was offer clinicians pragmatic recommendations that could be implemented immediately target this population. AASLD document differs guidelines, which are systematic reviews literature, formal rating quality evidence strength recommendations, and, if appropriate, meta‐analysis results using Grading Recommendations Assessment Development Evaluation system. In contrast, developed an expert provides statements based analysis topics, oversight provided Guidelines Committee at all stages development. The chose perform topic because sufficient number randomized controlled trials (RCTs) were not available support development guideline. Definitions Malnutrition, Frailty, Sarcopenia Their Relationship Patients With Cirrhosis major predisposing condition sarcopenia. Multiple, yet complementary, definitions these conditions exist domain outside field hepatology; but have been established Furthermore, there has ambiguity related operationalization constructs practice. To address this, we theoretical as commonly represented populations, partnered operational definitions, consensus, facilitate implementation applied cirrhosis (Table 1). Malnutrition syndrome "an imbalance (deficiency or excess) nutrients causes measurable adverse effects tissue/body form (body shape, size, composition) function, and/or outcome."(1) Key definition recognition malnutrition spectrum nutritional disorders across entire range body mass index (BMI)—from underweight obese. By definition, leads physical effects, which, cirrhosis, manifested phenotypically frailty Frailty most defined state decreased physiologic reserve increased vulnerability health stressors, its roots geriatrics.(2) However, weight date focused predominantly one component frailty: frailty. Although representation deviates somewhat classic "geriatric" global construct, manifestations impaired muscle contractile function reported such functional performance, disability. European Working Group "a progressive generalized skeletal disorder associated likelihood outcomes including falls, fractures, disability, mortality," combining both performance definition.(3) majority studies investigated measures alone. Therefore, phenotypic manifestation loss mass. Table 1 - Theoretical Constructs Consensus‐Derived Operational Applied Construct A deficiencies excesses nutrient intake, essential nutrients, use( 4 ) An outcome( stressors( 2 mortality( 3 have, purposes guidance, separate sarcopenia, acknowledge three interrelated often recognized simultaneously individual patient. For example, patient who presents clinic severe wasting might described "malnourished," "frail," "sarcopenic," each descriptor conveying similar information about patient's poor prognosis. Despite overlap practice, value understanding entity well relationship between order develop tailored behavioral interventions targeted pharmacotherapies conditions. Herein, propose conceptual framework (Fig. There factors lead challenging identify bedside unless it manifests only factor contributes sarcopenia; other complications, systems‐related (e.g., systemic inflammation, metabolic dysregulation), inactivity, environmental/organizational can contribute within independent pathway. addition, other—impaired accelerate vice versa. It phenotypes—frailty sarcopenia—that ultimately hepatic decompensation, care use, worse health‐related life, posttransplant outcomes, overall risk death.FIG. 1: Factors contributing constructs. Cirrhosis‐related factors, along inactivity malnutrition—which then These also directly independently malnutrition.Factors That Contribute Here, describe shown We are, some cases, interrelated; ease implementation, categorized broadly (1) (2) cirrhosis‐related, (3) systems–related, (4) (5) factors. Impaired Intake Macronutrients Reduced oral intake many early satiety, anorexia, nausea vomiting, dysgeusia, diet unpalatability low sodium potassium), level consciousness, free water restriction, frequent fasting due procedures hospitalizations.(5)Excess root cause obesity influenced variety biological, sociocultural, psychological factors.(6) Many limited knowledge disease self‐management, nutrition therapy.(7,8) Inadequate food knowledge/preparation skills insecurity impact dietary intake—through either reduced excess intake—across undernutrition obesity.(7‐9) Micronutrients Malabsorption high rates micronutrient deficiency leading macronutrient absorption micronutrients. particular, folate, thiamine, zinc, selenium, vitamin D, E alcohol‐associated liver disease; fat‐soluble documented cholestatic disease.(10‐14) Several micronutrients strong link Vitamin D general population.(15) evaluating role lacking, prevalent cirrhosis(16‐18) may progression Deficiency cofactor urea cycle metabolizes ammonium, HE, cirrhosis.(19‐21) Magnesium occurs malabsorption magnesium small intestine exacerbated diuretic use. cognitive adults cirrhosis(22‐24) bone resorption children disease.(25) Nutrient Uptake uptake multifactorial, resulting malabsorption, maldigestion, altered metabolism. Cholestasis alterations enterohepatic circulation bile salts maladaptation salt regulation. result elevated serum tissue levels potentially toxic metabolism long‐chain fatty acids children.(26‐28) Other contributors maldigestion include portosystemic shunting, pancreatic enzyme deficiency, bacterial overgrowth, intestinal flora, enteropathy.(5) Altered "accelerated starvation" glycogen synthesis storage during postprandial state, shift glycogenolysis gluconeogenesis, acid oxidation, whole‐body protein breakdown.(29,30) Hypermetabolism variably resting energy expenditure [REE] + SD REE:REE predicted 2SD).(31,32) catabolic hypermetabolism requirements, occurring least 15% without clear correlation severity predictors.(32,33) Cirrhosis‐Related itself through pathways. At pathophysiological level, needs intake. metabolism, particularly branched‐chain amino (BCAAs) supporting glutamine extrahepatic ammonia detoxification, circulating BCAAs, accelerated breakdown.(34‐36) clearance capacity, combination increases concentration pathologic muscle.(37‐39) Ammonia myotoxic mechanisms synthesis, autophagy, proteolysis, mitochondrial oxidative dysfunction muscle. Posttranslational modifications proteins bioenergetic mass.(40‐42) etiology differences prevalence sarcopenia.(43,44) affecting 80% decompensated cirrhosis—although approximately 60% NASH, chronic HCV, autoimmune hepatitis.(45) display rapid rate reduction areas compared etiologies.(43) Alcohol exposure inhibits proteasome activity, decreases anabolic hormone insulin‐like growth 1.(46‐48) secondary NASH additive insulin resistance inflammation.(49) Finally, cholestasis‐predominant diseases, primary sclerosing cholangitis, induce atrophy receptor G protein–coupled (or TGR5) expressed healthy muscles.(50) Complications portal hypertension dysfunction. HE hospitalizations.(37,51) Ascites REE, activity.(52,53) Both ascites strongly frailty.(54) Systems Systemic Inflammation, Endocrine Factors, Metabolic Dysregulation, Aging‐Related Conditions Circulating inflammatory markers IL‐1, IL‐6, IL‐10, C‐reactive protein, TNF‐α cirrhosis.(55,56) Low‐grade endotoxemia gut permeability, lipopolysaccharide cirrhosis‐related changes microbiome.(57) inflammation promote their subsequent complications degradation.(58‐61) Even absence developing Inflammatory cytokines HCV; eradication HCV antiviral agents decrease markers.(62,63) diseases NAFLDs characterized markers.(64) Further disruption mediators "liver–muscle axis" testosterone secretion sensitivity.(65) Low observed male nonsarcopenic.(66) Testosterone replacement resulted improvements total lean mass,(67) further Obesity increasing relevance given rapidly rising obesity‐related diseases.(6,68‐71) dysregulation, visceral fat accumulation, resistance, resistance. demonstrated nearly third meeting criteria (SMI).(70) regard although multicenter study awaiting transplantation did demonstrate significant interaction outcomes: BMI ≥ 35 kg/m2 frail experienced 3‐fold waitlist mortality similar‐weight nonfrail.(68) Consistent population, rise older adults.(72) (aging‐related) (chronic disease–related) referred "compound sarcopenia."(73) hospitalized patients, compound higher odds death (OR, 1.06; 95% CI, 1.04‐1.08) greater resource use 1.10; than sarcopenia.(73) Physical Inactivity sedentary behavior mortality.(74‐76) 53 transplant candidates, participants spent 76% waking hours time completed mean 3,000 steps per day.(76) significantly among candidates those transplant, removed social reasons, still waiting).(75) survey caregivers, caregivers feeling "encouraged exercise,"(77) suggesting possible barrier engaging activity patient–provider communication around benefits activity. no prospective longitudinal direct benefit increase (in counseling) mass, capacity.(78‐82) suggest may, part, decline Social Determinants Health determinants health—that is, where live, learn, work, play(83)—also play literacy primarily governed socioeconomic candidates.(84) Food owing poverty, isolation, access nutritious advanced NAFLD.(85) Financial strain limit caregiver presence home, monitoring, supervision less attentive timely lactulose therapy HE). Conversely, productivity earning potential. Some lose employment,(86) worsening financial thus ability provide adequate malnutrition. Organizational local, community, national exacerbate Community‐level barriers obesity, populations drive outcomes. pediatric recipients, neighborhood deprivation, administrative metric status, mortality.(87) Given complexity managing insufficient visits devote identifying strategies causes. referral to, comanagement with, registered dietician expertise ideal, systems allow follow‐up assess response treatment recommendations. confusion provider responsible physician, hepatologist, dietician), despite importance multimodal, multidisciplinary approach. Clinical Manifestations Muscle Dysfunction: Adults Children Tools multidimensional construct frailty) components status) studied listed 2.115‐128 tools organized table subjective, survey‐based assessed patient, caregiver, clinician objective, performance‐based assessments. ambulatory setting only, underscoring original reserve. prognostic two acute setting—activities daily living (ADLs) Karnofsky Performance Status (KPS)—highlights need measure complications. Assess Individual Components Studied Tool Setting Administration Time Equipment Needed Component(s) Measured Details Regarding Scale( 96,115 Ambulatory inpatient <1 minute None Global Rapid instrument assessment scale 1‐9 = very fit, 5 mildly frail, 9 terminally ill ADLs( 97,100,113 2‐3 minutes Ability conduct basic tasks one's home Patient assesses difficulty dependence six activities hygiene, eating, ambulation) KPS( 88,89,116,117 carry out normal ADLs Patient, limitations ranging 100 (normal, complaints, disease) 50 (requires considerable assistance medical care) 10 (moribund, fatal processes progressing rapidly). Lansky Play‐Performance 94 Usual aged 1‐17 years transplant. Similar KPS (fully active, normal) (lying much day, active playing participates quiet activities) (does play) Eastern Cooperative Oncology Group( 103,104,118‐121 0‐5, 0 asymptomatic, < 50% bed bedbound. Fried Instrument( 75,106 5‐10 Hand dynamometer,stopwatch,tape Consists five domains: (question), exhaustion slowness (short gait speed), weakness (hand grip strength), (questionnaire) Modified 93 60 Developed 5‐17 years. (triceps skinfold thickness), (questionnaire), (gait (grip strength( 122,123 dynamometer asked dominant hand best effort. test repeated times, values averaged. Short speed( 105 ~1 stopwatch, tape Functional mobility One Battery 6‐minute walk test( 107 6 Stopwatch, Submaximal aerobic capacity endurance Distance walked flat surface usual walking speed Battery( 75 ~3 Stopwatch,tape measure, chair Lower extremity components: 8‐foot speed, timed stands (5 times), balance testing positions (feet together, semitandem, tandem) seconds Index( 54,90‐92,124‐127 dynamometer, Cirrhosis‐specific tool consisting strength, stands, testing. Changes Index Cardiopulmonary exercise 102,108,128 stress diagnostic system Maximal Noninvasive measurement gas exchange rest evaluate submaximal peak responses scales validated thresholds grade Specifically, having high, moderate, status 80‐100, 50‐70, 10‐40, respectively.(88,89) cut‐points define robust (Liver 3.2), prefrail 3.2‐4.3), 4.4).(90,91) Poor according ADLs), however, suggests burden deficits others speed). evaluated associations assessments Index.(88,92) When comes assessing children, well‐established administer participation tests (either performance) consideration age‐related sex‐related norms. few concept applicability disease. traditional phenotype, ages, modified children.(93) feasible cohort age, undergoing too young Instrument (median age 18 years), highlighting derive objective age. promising Scale, cancer 1‐16 years, provider.(94) Gaps remain year Prevalence Natural History cirrhosis; severity. Estimates population varied different capture function. Among setting, ranged 17% 43%.(54,75,95,96) 38% inpatients (and 18% HE) measured disability ADL tool.(97,98) Rates 68% scale.(89) Using Instrument, 24% met 46% more advanced/end‐stage disease.(93) worsens over time.(88,92) United States, 20% displayed improved stable scores.(88) After transplantation, 90% improvement
Язык: Английский
Процитировано
446
Current Osteoporosis Reports, Год журнала: 2020, Номер 18(4), С. 388 - 400
Опубликована: Июнь 12, 2020
Язык: Английский
Процитировано
375
EBioMedicine, Год журнала: 2019, Номер 49, С. 381 - 388
Опубликована: Окт. 26, 2019
As our population grows older, age-related pathologies are becoming more prevalent. Deterioration of skeletal muscle and the immune system manifests as sarcopenia senescence respectively. The disease burden these emphasizes need for a better understanding underlying mechanisms. Skeletal has emerged potent regulator function. such, might be central integrator between in an aging biological system. Therapeutic approaches targeting able to restore both In this review, we therefore outline current - however still fragmentary knowledge about potential communication pathways system, how they affected by discuss possible treatment strategies. review intends hypothesis-generating should thereby stimulate further research important scientific field.
Язык: Английский
Процитировано
343
GeroScience, Год журнала: 2020, Номер 42(6), С. 1547 - 1578
Опубликована: Окт. 1, 2020
The COVID-19 pandemic is an extraordinary global emergency that has led to the implementation of unprecedented measures in order stem spread infection. Internationally, governments are enforcing such as travel bans, quarantine, isolation, and social distancing leading extended period time at home. This resulted reductions physical activity changes dietary intakes have potential accelerate sarcopenia, a deterioration muscle mass function (more likely older populations), well increases body fat. These composition associated with number chronic, lifestyle diseases including cardiovascular disease (CVD), diabetes, osteoporosis, frailty, cognitive decline, depression. Furthermore, CVD, elevated fat greater risk infection more severe symptomology, underscoring importance avoiding development morbidities. Here we review mechanisms sarcopenia their relation current data on effects confinement activity, habits, sleep, stress bed rest due hospitalization. these factors lead increased likelihood loss chronic will be discussed. By offering home-based strategies resistance exercise, higher protein supplementation, can potentially guide public health authorities avoid rehabilitation crisis post-COVID-19. Such may also serve useful preventative for reducing general event future periods isolation.
Язык: Английский
Процитировано
302
Ageing Research Reviews, Год журнала: 2020, Номер 65, С. 101200 - 101200
Опубликована: Окт. 30, 2020
Sarcopenia represents a muscle-wasting syndrome characterized by progressive and generalized degenerative loss of skeletal muscle mass, quality, strength occurring during normal aging. patients are mainly suffering from the in faced with mobility disorders reducing their quality life are, therefore, at higher risk for morbidity (falls, bone fracture, metabolic diseases) mortality. Several molecular mechanisms have been described as causes sarcopenia that refer to very different levels physiology. These cover e. g. function hormones (e. IGF-1 Insulin), fiber composition neuromuscular drive, myo-satellite cell potential differentiate proliferate, inflammatory pathways well intracellular processes proteostasis mitochondrial function. In this review, we describe distinct other atrophic diseases summarize current view on development open questions provoking further research efforts establishing efficient lifestyle therapeutic interventions.
Язык: Английский
Процитировано
301
Experimental Gerontology, Год журнала: 2019, Номер 131, С. 110801 - 110801
Опубликована: Дек. 27, 2019
Sarcopenia shares risk factors with various other age-related diseases. This meta-analysis aimed to determine the prevalence of sarcopenia as a comorbid disease. Medline, EMBASE and Cochrane databases were searched for articles from inception 8th June 2018, reporting in individuals diagnosis cardiovascular disease (CVD), dementia, diabetes mellitus or respiratory and, if applicable their controls. No exclusion criteria applied regards definition sarcopenia, individuals' age, study design setting. Meta-analyses stratified by disease, continent. The 63 included described 17,206 diseased (mean age: 65.3 ± 1.6 years, 49.9% females) 22,375 non-diseased controls 54.6 16.2 53.8% females). CVD was 31.4% (95% CI: 22.4–42.1%), no available. 26.4% 13.6–44.8%) dementia compared 8.3% 2.8–21.9%) controls; 31.1% 19.8–45.2%) 16.2% 9.5–26.2%) 26.8% 17.8–38.1%) diseases 13.3% 8.3–20.7%) is highly prevalent CVD,
Язык: Английский
Процитировано
273
Journal of Cachexia Sarcopenia and Muscle, Год журнала: 2020, Номер 11(3), С. 619 - 635
Опубликована: Март 6, 2020
Abstract Cancer cachexia is a multifactorial syndrome characterized by progressive loss of skeletal muscle mass, along with adipose tissue wasting, systemic inflammation and other metabolic abnormalities leading to functional impairment. has long been recognized as direct cause complications in cancer patients, reducing quality life worsening disease outcomes. Some related conditions, like sarcopenia (age‐related wasting), anorexia (appetite loss) asthenia (reduced muscular strength fatigue), share some key features cachexia, such weakness inflammation. Understanding the interplay differences between these conditions critical advance basic translational research this field, improving accuracy diagnosis contributing finally achieve effective therapies for affected patients.
Язык: Английский
Процитировано
269
Nutrients, Год журнала: 2020, Номер 12(6), С. 1755 - 1755
Опубликована: Июнь 11, 2020
Muscle health is important for the functionality and independence of older adults, certain nutrients as well dietary patterns have been shown to offer protective effects against declines in strength function associated with aging. In this paper, micronutrients, macronutrients, food groups reviewed, along their studied on prevalence incidence sarcopenia, ability preserve muscle mass optimize physical performance. Randomized controlled trials appear suggest a critical role intake protein preventing sarcopenia loss, although optimal dose type unknown. There are some promising data regarding vitamin D but it unclear whether dose, frequency or length treatment impacts efficacy improving function. Selenium, magnesium, omega 3 fatty acids supplements clinical diet, they demonstrate potential association activity performance individuals. Following Mediterranean diet higher consumption fruits vegetables improved protection wasting, frailty.
Язык: Английский
Процитировано
265
Journal of Cachexia Sarcopenia and Muscle, Год журнала: 2021, Номер 12(6), С. 1393 - 1407
Опубликована: Сен. 14, 2021
Язык: Английский
Процитировано
224