Association of Handgrip Strength and Muscle Mass with Dependency in (Instrumental) Activities of Daily Living in Hospitalized Older Adults -The EMPOWER Study.

OBJECTIVES: Handgrip strength (HGS) and muscle mass are strong predictors for dependency in Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) in community dwelling older adults. Whether this also applies to older hospitalized patients is yet unknown. We studied the association between HGS and muscle mass with ADL and IADL dependency at admission and change of ADL and IADL dependency at three months after discharge in older hospitalized patients. DESIGN: Observational longitudinal inception cohort (EMPOWER) including 378 patients aged 70 years and older. SETTING: Four different clinical wards of a university teaching hospital, The Netherlands. MEASUREMENTS: HGS and muscle mass were measured within 48 hours after admission using hand dynamometry and Bio-electrical Impedance Analysis respectively. ADL dependency was assessed using the Katz score (0-6 points) and IADL dependency using the Lawton and Brody score (0-8 points) within 48 hours after admission and three months after discharge. RESULTS: At admission, lower HGS was associated with ADL dependency in both males and females. Lower muscle mass was associated with ADL dependency in males. Lower HGS was associated with IADL dependency, but only in males. Lower HGS at admission in males was associated with an increase in ADL dependency three months after discharge. CONCLUSION: In hospitalized older patients, HGS is associated with ADL and IADL and muscle mass measures with ADL in male patients only. HGS should be explored as predictive marker for outcome of hospitalized older patients after discharge.

Muscle, Health and Costs: A Glance at their Relationship.

OBJECTIVE: To assess the association between muscle parameters (mass, strength, physical performance) and activities of daily living (ADL), quality of life (QoL), and health care costs. DESIGN: Cross-sectional Maastricht Sarcopenia Study (MaSS). SETTING: Community-dwelling, assisted-living, residential living facility. PARTICIPANTS: 227 adults aged 65 and older. MEASUREMENTS: Muscle mass, hand grip strength and physical performance were assessed by bio-electrical impedance, JAMAR dynamometer and the Short Physical Performance Battery, respectively. Health outcomes were measured by the Groningen Activity Restriction Scale (disability in ADL) and the EQ-5D-5L (QoL). Health care costs were calculated based on health care use in the past three months. RESULTS: Muscle strength and physical performance showed a strong correlation with ADL, QoL, and health care costs (P<.01); for muscle mass no significant correlations were observed. Regression analyses showed that higher gait speed (OR 0.06, 95%CI 0.01-0.55) was associated with a lower probability of ADL disability. Furthermore, slower chair stand (OR 1.23, 95%CI 1.08-1.42), and more comorbidities (OR 1.58, 95%CI 1.23-2.02) were explanatory factors for higher ADL disability. Explanatory factors for QoL and costs were: more disability in ADL (OR 1.26, 95%CI 1.12-1.41 for QoL; B = 0.09, P<.01 for costs) and more comorbidities (OR 1.44, 95%CI 1.14-1.82 for QoL; B = 0.35, P<.01 for costs). CONCLUSION: Lower gait speed and chair stand were potential drivers of disability in ADL. Disability in ADL and comorbidities were associated with QoL and health care costs in community-dwelling older adults. Improving physical performance may be a valuable target for future intervention and research to impact health burden and costs.

Muscle Measures and Nutritional Status at Hospital Admission Predict Survival and Independent Living of Older Patients - the EMPOWER Study.

OBJECTIVES: Older adults with sarcopenia and malnutrition are at risk for co-morbidities, hospitalization, institutionalization, and mortality. In case of hospitalization, risks may be further increased, especially in case of suboptimal dietary intake. The aim of our study was to assess whether muscle mass, muscle strength, functional performance, and nutritional status at hospital admission were associated with survival and independent living among older patients three months after discharge. DESIGN, SETTING, PARTICIPANTS: The EMPOWER study was an observational, prospective and longitudinal inception cohort of patients older than 70 years admitted to the VU University Medical Centre in Amsterdam, the Netherlands. MEASUREMENTS: Patients were assessed for demographic and clinical characteristics, measurements of muscle mass (by bioelectrical impedance analysis), handgrip strength (by dynamometry), functional performance (self-reported ability to walk), and screened for risk of malnutrition (by SNAQ). Three months after hospital discharge, survival and living situation were assessed by a follow-up telephone interview. RESULTS: The majority of the 378 patients enrolled were living independently at the time of hospitalization (90%) and three months post-discharge (83%). Fifty-two patients died in the period from hospital admission to three months after discharge (survival rate 86%). Higher absolute muscle mass measures and not being malnourished at admission were significantly associated with the likelihood of survival. Handgrip strength and self-reported ability to walk were positively associated with a higher chance of living independently three months after discharge, but not with survival. CONCLUSIONS: Older patients with greater muscle mass and without malnutrition at hospital admission had a higher survival rate, while measures of muscle strength and functional performance were predictive for living independently three months after hospital discharge. Different components of muscle health relate to different relevant outcomes and therefore require investigation of specifically targeted interventions in the hospitalized older population.

Functional human monoclonal antibodies of all isotypes constructed from phage display library-derived single-chain Fv antibody fragments.

We have constructed a series of eukaryotic expression vectors that permit the rapid conversion of single chain (sc) Fv antibody fragments, derived from semi-synthetic phage display libraries, into intact fully human monoclonal antibodies (mAb) of each isotype. As a model, a scFv fragment specific for sheep red blood cells (SRBC) was isolated from a semi-synthetic phage antibody (Ab) display library, and used to produce human mAbs of IgM, IgG1-IgG4, IgA1, IgA2m(1) and IgE isotype in vitro in stably transfected cells. N-terminal protein sequence analysis of purified immunoglobulin heavy (H) and light (L) chains revealed precise proteolytic removal of the leader peptide. Biochemical analysis of purified recombinant human mAbs demonstrated that properly glycosylated molecules of the correct molecular size were produced. The IgG and IgA mAbs retained SRBC-binding activity, interacted with different Fc receptor-transfectants, and induced complement-mediated hemolysis and Ab-dependent phagocytosis of SRBC by neutrophils in a pattern consistent with the immunoglobulin (Ig) H chain isotype. We conclude that in vitro produced recombinant human mAbs constructed from phage display library-derived scFv fragments mirror their natural counterparts and may represent a source of mAbs for use in human therapy.