Ultrasound quadriceps muscle thickness is variably associated with frailty in haemodialysis recipients.

BACKGROUND: Ultrasonographic quantitation of quadriceps muscle mass is increasingly used for assessment of sarcopenia, but its relationship with frailty in haemodialysis recipients is not known. This study explores the relationship between ultrasound-derived bilateral anterior thigh thickness (BATT), sarcopenia, and frailty by common frailty tools (Frailty Phenotype [FP], Frailty Index [FI], Edmonton Frailty [EFS], and Clinical Frailty Scale [CFS]). METHODS: This was an exploratory analysis of a subgroup of adult prevalent (≥3 months) haemodialysis recipients deeply phenotyped for frailty. Ultrasound assessment of BATT was obtained with participants at an angle of ≤45°, with legs outstretched and knees resting at 10°-20°, according to an established protocol. Associations with frailty were explored via both linear and logistic regressions for BATT, Low Muscle Mass (LMM), and sarcopenia with stepwise adjustment for a priori covariables. RESULTS: In total 223 study participants had ultrasound measurements. Frailty ranged from 34% for FP to 58% for FI. BATT was associated with increasing frailty on simple linear regression by all frailty tools, but lost significance on addition of covariables. Upon dichotomising frailty tools into Frail/Not Frail, BATT was associated with frailty by all tools on univariable analyses, but only retained association for EFS on the fully adjusted model (OR 0.97, 95% C.I. 0.94-1.00, P = 0.05). CONCLUSIONS: Ultrasound measures of quadriceps thickness is variably associated with frailty in prevalent haemodialysis recipients, dependent upon the frailty tool used, but not independent of other variables. Further work is required to establish the added value of sarcopenia measurement in frail haemodialysis patients. TRIAL REGISTRATION: Clinicaltrials.gov : NCT03071107 registered 06/03/2017.

Gender Disparity in Expression of Sarcopenia in Haemodialysis Recipients: Analysis from the FITNESS Cohort.

Background: There has been little exploration of the interplay between sarcopenia and frailty in haemodialysis, particularly regarding gender difference. We aimed to (1) assess whether ultrasound-derived low muscle mass (LMM) and sarcopenia are more common in male or female haemodialysis recipients; (2) assess whether age influences any observed gender difference, and (3) explore the interplay between sarcopenia, frailty, and gender in haemodialysis recipients. Methods: This was an exploratory analysis of a subgroup of adult prevalent (≥3 months) haemodialysis with frailty phenotype (FP) scores. Bilateral anterior thigh thickness (BATT) was obtained according to an established ultrasound protocol. Associations with frailty were explored via both linear and logistic regressions for BATT, LMM, and sarcopenia with a priori covariables, stratified by gender. Results: In total of 223 studies, participants had ultrasound measurements. Males showed greater prevalence of LMM. On adjusted analyses, LMM was associated with lower hand grip strength in males (ß = -4.17; 95% C.I. -7.57 to -0.77; P=0.02), but not females (ß = -1.88; 95% C.I. -5.41 to 1.64; P=0.29). LMM was also associated with slower walking speed in both males (ß = -0.115; 95% C.I. -0.258 to -0.013; P=0.03) and females (ß = -0.152; 95% C.I. -0.300 to -0.005; P=0.04). Sarcopenia was associated with greater odds of frailty on adjusted models in males (OR = 9.86; 95% C.I. 1.8 to 54.0; P=0.01), but not females (OR = 5.16; 95% C.I. 0.22 to 124; P=0.31). Conclusions: The clinical expression and significance of sarcopenia differ substantially between males and females on haemodialysis. Further work is required to elucidate underlying mechanisms and guide tailored treatment.

Innate immune cells in liver inflammation.

Innate immune system is the first line of defence against invading pathogens that is critical for the overall survival of the host. Human liver is characterised by a dual blood supply, with 80% of blood entering through the portal vein carrying nutrients and bacterial endotoxin from the gastrointestinal tract. The liver is thus constantly exposed to antigenic loads. Therefore, pathogenic microorganism must be efficiently eliminated whilst harmless antigens derived from the gastrointestinal tract need to be tolerized in the liver. In order to achieve this, the liver innate immune system is equipped with multiple cellular components; monocytes, macrophages, granulocytes, natural killer cells, and dendritic cells which coordinate to exert tolerogenic environment at the same time detect, respond, and eliminate invading pathogens, infected or transformed self to mount immunity. This paper will discuss the innate immune cells that take part in human liver inflammation, and their roles in both resolution of inflammation and tissue repair.

Bilateral Anterior Thigh Thickness: A New Diagnostic Tool for the Identification of Low Muscle Mass?

OBJECTIVES: To develop an ultrasonographic scanning protocol that included an assessment of muscle size [the proposed Bilateral Anterior Thigh Thickness (BATT)] and quality (echogenicity) to support the diagnosis of sarcopenia in a clinical setting. To determine the relationship of BATT and ultrasound echogenicity with physical function parameters of sarcopenia and test the reliability of ultrasound echogenicity measurements. DESIGN: Observational study. SETTING AND PARTICIPANTS: The BATT criteria were determined from a reference population of 113 healthy younger adults and tested in 39 healthy older adults and 31 frail older adults. METHODS: Ultrasonography was used to measure the thickness of rectus femoris and vastus intermedius bilaterally; the thickness measurements were summed to calculate the BATT. Diagnostic criteria for low muscle size were calculated from the reference population. Echogenicity was assessed using freeze-frame images. All individuals underwent anthropological, frailty, and physical performance assessments. RESULTS: The mean (standard deviation) BATTs for the subsamples were as follows: healthy young women (n = 54), 60.6 mm (±11.1); healthy young men (n = 59), 75.8 mm (±10.71); healthy older women (n = 27), 38.4 mm (±7.18); healthy older men (n = 13), 47.5 mm (±10.8); frail older women (n = 17), 29.2 mm (±11.4); and frail older men (n = 14), 27.3 mm (±13.9). The calculated cutoffs for low muscle size in older adults using the BATT criteria were 38.5 mm in women and 54.4 mm in men in this population. The BATT was correlated with grip strength (ρ = 0.750, P < .001 for women; ρ = 0.619, P < .001 for men) and walk speed (ρ = -0.599, P < .001 for women; ρ = -0.324, P = .003 for men). Ultrasound echogenicity increased with age and frailty. Lay sonographers were able to reliably reproduce the same muscle thickness measurements but not the same muscle echogenicity measurements. CONCLUSIONS/IMPLICATIONS: The data support the use of ultrasonography to identify low muscle size in sarcopenia. Ultrasonography provides a pragmatic diagnostic tool that is noninvasive, without radiation exposure, and usable in both community and hospital settings. The proposed BATT criteria could be used to identify low muscle size in clinical practice and research, and in this study have excellent correlation with physical parameters of muscle health. However, this now needs testing in a validation cohort. Ultrasound echogenicity has been demonstrated to be an important surrogate marker of muscle health, but difficulties with reproducibility preclude its widespread clinical use.

Inflammation and neutrophil immunosenescence in health and disease: Targeted treatments to improve clinical outcomes in the elderly.

Despite increasing longevity, many old people are not in good health. There has been an increase in the prevalence of age-associated multi-morbidity (two or more chronic conditions in the same person). Also, severe infections, such as pneumonia, remain significant causes of mortality and morbidity in this aging group. Many chronic health conditions share risk factors such as increasing age, smoking, a sedentary life style and being part of a lower socioeconomic group. However, despite this, multi-morbidities often co-occur more commonly than would be predicted. This has led to the hypothesis that they share common underlying mechanisms. This is an important concept, for if it were true, treatments could be devised which target these common pathways and improve a number of age-associated health conditions. Many chronic illnesses associated with multi-morbidity and severe infections are characterized by an abnormal and sustained inflammatory response, with neutrophils being key effector cells in the pathological process. Studies have described aberrant neutrophil functions across these conditions, and some have highlighted potential mechanisms for altered cell behaviours which appear shared across disease states. It has been suggested that altered functions may represent neutrophil "senescence". This review considers how and why neutrophil functions change as the cell ages, and how and why neutrophil functions change as the host ages in health and disease and discusses whether neutrophil functions could be targeted to improve health outcomes in older adults.