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Purpose: Little is known about the relationships between apathy, depressive symptoms and interdialytic weight gain (IDWG) in patients on chronic hemodialysis. Aim of the present study is to investigate the association between IDWG and symptoms of depression and apathy in hemodialysis patients. Methods: A total of 139 chronic patients of the HD units between January 2020 and December 2021 were included in the present cross-sectional study. IDWG was calculated as the difference between the pre-HD weight and the weight registered after the previous session; the average of the sessions in a month was registered. Apathy Evaluation Scale (AES) was adopted to evaluate apathy. Depression was assessed by Beck Depression Inventory (BDI). Results: Ninety-three patients had IDWG% ≤ 4 and 46 had an IDWG% > 4. Correlation between IDWG% and BDI as well that between IDWG% and AES were not statistically significant. Median BDI and mean AES did not differ significantly between the groups. In addition, 104 patients had a BDI < 16 and 35 had a BDI ≥ 6. Seventy-five patients had an AES score ≤ 35 and 63 had a AES score > 35. The IDWG (kg) and the IDWG% did not differ significantly between the two groups. Conclusion: IDWG is not associated with symptoms of depression or apathy in hemodialysis patients. Thus, these results may question if the use of behavioral intervention aimed at improving motivation is warranted in the hemodialysis population to reduce the IDWG.

Fatigue is still present in up to 40–50% of kidney transplant recipients (KTR), the results of studies comparing the prevalence among patients on hemodialysis (HD) and KTR led to conflicting results. Fatigue correlates include inflammation, symptoms of depression, sleep disorders and obesity. Fatigue in KTR leads to significant functional impairment, it is common among KTR poorly adherent to immunosuppressive therapy and is associated with a serious deterioration of quality of life. The following databases were searched for relevant studies up to November 2020: Medline, PubMed, Web of Science and the Cochrane Library. Several studies have compared the prevalence and severity of fatigue between KTR and hemodialysis or healthy patients. They have shown that fatigue determines a significant functional deterioration with less chance of having a paid job and a significant change in quality of life. The aim of the review is to report methods to assess fatigue and its prevalence in KTR patients, compared to HD subjects and define the effects of fatigue on health status and daily life. There is no evidence of studies on the treatment of this symptom in KTR. Efforts to identify and treat fatigue should be a priority to improve the quality of life of KTR.

Whether hemodiafiltration (HDF) is better than conventional hemodialysis (HD) in improving left ventricular hypertrophy (LVH), defined as reduction of the left ventricular mass index (LVMi) and increasing the ejection fraction (EF), is unclear. A systematic literature search was performed. Primary outcome was the mean difference between pre- and post-procedural LVMi. Secondary outcome was the mean difference in EF. Seven studies with a total of 845 patients were included. The pooled mean difference between pre-and post-procedural LVMi was −8.0 g/m2 (95% confidence interval [CI] −13.1, −2.8). On subgroup analysis, the mean differences between pre- and post-procedural LVMi for HD and HDF were −6.7 g/m2 (95% CI −14.5, 1.1) and −9.3 g/m2 (95% CI −16.3, −2.3), respectively (P for subgroups =.62). Pooled mean difference between pre- and post-procedural EF was 2.4% (95% CI −1.8, 6.5). On subgroup analysis, the mean differences between pre- and post-procedural EF for HD and HDF were 3.6% (95% CI −2.7, 9.8) and 2.0% (95% CI 2.9, 6.8), respectively (P for subgroups =.68). On meta-regression, age (Beta −0.35 ± 0.05, P <.001) and longer dialysis duration (Beta −0.12 ± 0.02, P <.001) were associated with lower mean difference between pre-and post-procedural EF. No significant effects on changes in LVMi and EF were observed with HDF compared with conventional HD.

Background This work aimed to shed light on the notorious debate over the role of an educational/cognitive/behavioral or psychological approach in the reduction of interdialytic weight gain (IDWG) in patients on chronic hemodialysis.Methods Searches were run from 1975 to January 2022 on Medline, PubMed, Web of Science, and the Cochrane Library. The search terms included "hemodialysis/haemodialysis" AND "adherence" AND ("fluid intake" OR "water intake") AND ("weight gain" OR "interdialytic weight gain" OR "IDWG") AND "patient-level interventions. Randomized controlled studies were eligible if they were in English, published in a peer-reviewed journal and regarded adults patients with on chronic hemodialysis for at least 6 months; compared educational/cognitive and/or counseling/behavioral or psychological interventions to no intervention on interdialytic weight gain. Outcome of interest was interdialytic weight gain. The review was registered on the International Prospective Register of Systematic Reviews in Health and Social Care (PROSPERO, ID number CRD42022332401).Results Eighteen studies (1759 patients) were included in the analysis. Compared to the untreated group, educational/cognitive and/or counseling/behavioral interventions significantly reduced interdialytic weight gain with a pooled mean difference of - 0.15 kg (95% CI - 0.26, 30-0.05; P = 0.004). On the other hand, psychological/affective interventions reduced interdialytic weight gain with a pooled mean difference of - 0.26 kg (95% CI - 0.48, - 0.04; P = 0.020).Conclusions Educational/cognitive, counseling/behavioral or psychological/affective interventions significantly reduced the interdialytic weight gain in patients on chronic hemodialysis, although such reduction did not appear to be clinically relevant on hard outcomes.

Introduction: This study explores the link between fatigue and apathy in patients on chronic hemodialysis (HD). Methods: One hundred thirty-nine chronic HD patients underwent the assessment of fatigue, apathy, depression, and their functional status, with the fatigue severity scale (FSS), the Apathy Evaluation Scale (AES), the beck depression inventory (BDI), the activity of daily living (ADL), and instrumental activity of daily living (IADL). Results: Patients with high FSS had a significantly lower ADL and IADL score, higher BDI, Charlson Comorbidity Index, and AES score, and lower serum levels of creatinine, compared to low FSS patients. FSS was highly correlated with the AES, as well as with the BDI and the AES correlates with the BDI. At multiple regression analyses, only apathy and IADL were independent predictor variables of fatigue in HD population. Conclusion: Future longitudinal studies could determine if apathy is a causative factor for fatigue manifestation and development in HD patients.

Patients affected by chronic kidney disease (CKD) have an increased risk of developing cognitive impairment. The cause of mental health disorders in CKD and in chronic hemodialysis patients is multifactorial, due to the interaction of classical cardiovascular disease risk factors, kidney- and dialysis-related risk factors with depression, and multiple drugs overuse. A large number of compounds, defined as uremic toxins that normally are excreted by healthy kidneys, accumulate in the circulations, in the tissues, and in the organs of CKD patients. Among the candidate uremic toxins are several guanidino compounds, such as Guanidine. Uremic toxins may also accumulate in the brain and may have detrimental effects on cerebral resident cells (neurons, astrocytes, microglia) and microcirculation. The present study aims to analyze the effect of Guanidine on hippocampal excitatory postsynaptic field potentials (fEPSPs) and in CA1 pyramidal neurons recorded intracellularly. Moreover, we compared these effects with the alterations induced in vitro by CKD patients derived serum samples. Our results show an increased, dose-dependent, synaptic activity in the CA1 area in response to both synthetic Guanidine and patient’s serum, through a mechanism involving glutamatergic transmission. In particular, the concomitant increase of both NMDA and AMPA component of the excitatory postsynaptic currents (EPSCs) suggests a presynaptic mechanism. Interestingly, in presence of the lower dose of guanidine, we measure a significant reduction of EPSCs, in fact the compound does not inhibit GABA receptors allowing their inhibitory effect of glutamate release. These findings suggest that cognitive symptoms induced by the increase of uremic compounds in the serum of CKD patients are caused, at least in part, by an increased glutamatergic transmission in the hippocampus.

Context: Poor quality of life is a major problem in hemodialysis patients. Objectives: This study was conducted to assess the effect of aromatherapy massage on hemodialysis patients' quality of life. Methods: In this parallel randomized clinical trial study, 105 hemodialysis patients who meet the inclusion criteria were assessed and assigned into intervention and control groups using block randomization. Participants in the intervention groups received aromatherapy massage with Lavender essential oil or Citrus Aurantium essential oil for four weeks (three times per week). For the control group, only foot massage was performed. The level of quality of life was measured by the 36-Item Short-Form Health Survey questionnaire (SF-36) before and after the intervention. Data analysis was performed using descriptive and inferential statistics (analysis of variance, chi-square, and Fisher's exact tests). Results: There was a significant difference between the mean score of quality of life in the Lavender essential oil group and Citrus Aurantium essential oil group with the control group after intervention. However, there was no significant difference between the mean score of quality of life in the Lavender essential oil group and Citrus Aurantium essential oil group after the intervention. Conclusions: In this study, both aromatherapy massages have positive effects on the quality of life of hemodialysis patients. Therefore, nurses are advised to use these aromatherapy massages to improve the quality of life of hemodialysis patients.

Objective Fatigue and depressed mood are considered main impediments to physical activity in haemodialysis (HD) patients. A better understanding of their interrelationships is crucial to develop effective therapies. Moreover, measurement of daily physical activity (DPA) in HD patients is tricky, as it is usually assessed by subjective self-report questionnaires. Therefore, we aimed to objectively measure sponteanous DPA with motion sensors and to explore its relation with fatigue and depressive symptoms. Methods DPA was assessed for seven consecutive days in 37 HD patients based on their daily step count measured with the SenseWearTM Armband. The Fatigue Severity Scale (FSS) and Beck Depression Inventory-II (BDI-II) were administered to evaluate fatigue and depressed mood. Results Median DPA was 2424 steps/day, (IQR:892–4545). In 81% of subjects, DPA felt within a sedentary lifestyle classification, as they made < 5.000 steps/day. DPA did not correlate with fatigue (rs = 0.04, p = 0.832), and did not significantly differ between patients categorized as clinically fatigued (n = 23, FSS ≥ 4) or not (n = 14, FSS < 4) (p = 0.654, d = 0.20). Although low-depressed subjects (n = 19, BDI-II ≤ 13) made on average 1.7 times more steps/day than high-depressed subjects (n = 18, BDI-II > 13) (p = 0.111, d = 0.60), depressive mood did also not correlate significantly with DPA (rs = − 0.23, p = 0.175). Conclusion Objective assessment of DPA with motion sensors is feasible in HD patients and allows identifying a sedentary lifestyle. Our results suggest that spontanous DPA is determined by age rather than by fatigue or mood.

Thirst has been defined as “the sensation that leads animal’s and human’s actions toward the goal of finding and drinking water” or as “any drive that can motivate water intake, regardless of cause”. Thirst, together with xerostomia, is the main cause of poor adherence to fluid restriction and of excessive intake of fluids in patients on chronic hemodialysis, and consequently of high interdialytic weight gain. Interdialytic weight gain (IDWG) should be lower than 4.0–4.5% of dry weight. Unfortunately, many patients have an IDWG greater than this value and some have IDWG of 10–20%. High IDWG is associated with a higher risk of all-cause and cardiovascular death and increased morbidity, such as ventricular hypertrophy and major adverse cardiac and cerebrovascular events. In addition, high IDWG leads to supplementary weekly dialysis sessions with consequent deterioration of quality of life and increased costs. Thus, the knowledge of thirst in patients on chronic hemodialysis is essential to prompt its adequate management to limit IDWG in the routine clinical practice. The present review aims to describe the physiology of thirst in patients on chronic hemodialysis, as well as the prevalence, its measures, the associated variables, the consequences, and the strategies for its reduction.

Background: To measure daily sodium intake in patients on chronic hemodialysis and to compare the intake of nutrients, minerals, trace elements, and vitamins in patients who had a daily sodium intake below or above the value of 1500 mg recommended by the American Heart Association. Methods: Dietary intake was recorded for 3 days by means of 3-day diet diaries in prevalent patients on chronic hemodialysis. Each patient was instructed by a dietitian on how to fill the diary, which was subsequently signed by a next of kin. Results: We studied 127 patients. Mean sodium intake (mg) was 1295.9 ± 812.3. Eighty-seven (68.5%) patients had a daily sodium intake <1500 mg (group 1) and 40 (31.5%) ≥ 1500 mg (group 2). Correlation between daily sodium intake and daily calorie intake was significant (r = 0.474 [0.327 to 0.599]; p < 0.0001). Daily calorie intake (kcal/kg/day) was lower in group 1 (21.1 ± 6.6; p = 0.0001) than in group 2 (27.1 ± 10.4). Correlation between daily sodium intake and daily protein intake was significant (r = 0.530[0.392 to 0.644]; p < 0.0001). The daily protein intake (grams/kg/day) was lower in group 1 (0.823 ± 0.275; p = 0.0003) than in group 2 (1.061 ± 0.419). Daily intake of magnesium, copper, iron, zinc, and selenium was significantly lower in group 1 than in group 2. Daily intake of vitamin A, B2, B3, and C did not differ significantly between group 1 and group 2. Daily intake of vitamin B1 was significantly lower in group 1 than in group 2. Significantly lower was, in group 1 than in group 2, the percentage of patients within the target value with regard to intake of calories (11.5% vs. 37.5%; p = 0.001) and proteins (9.2% vs. 27.5%; p = 0.015) as well as of iron (23% vs. 45%; p = 0.020), zinc (13.8% vs. 53.8%; p = 0.008) and vitamin B1 (8.1% vs. 50%; p < 0.001). Conclusion: A low daily intake of sodium is associated with an inadequately low intake of calorie, proteins, minerals, trace elements, and vitamin B1. Nutritional counselling

Background: Although frequent and debilitating, little is known about the characteristics of post-dialysis fatigue (PDF). Objective: To characterise the intensity, duration and frequency of PDF and the associated variables in patients on chronic haemodialyses. Design: Prospective, observational and multicenter study. Patients: We studied 271 patients. Measurements: Patients were considered to be suffering from PDF if they spontaneously offered this complaint when asked the open-ended question: “Do you feel fatigued after dialysis? Then, each patient was invited to rate the intensity, duration and frequency of PDF from 1 to 5. Results: One hundred sixty-four patients (60.5%) had PDF. The median [95% confidence interval (CI)] scores of PDF intensity, duration and frequency were 3 (3–4), 3 (3–4) and 4 (4-4), respectively. The median (95% CI) of the sum of the scores (Sum Score) of PDF intensity, duration and frequency was 11 (10–12). Seventy four patients had a Sum Score ≥ 12. Using multiple regression analysis, PDF intensity was associated with dialytic age and ultrafiltration rate (UFR), PDF duration with dialytic age, while PDF fatigue frequency was associated with height. The Sum Score was associated with dialytic age and recovery time and negatively associated with daily activity, height and UFR (ml/kg/h). Conclusion: The intensity, duration and frequency of PDF are high in a large percentage of patients, suggesting that PDF is an intense event in terms of quantity and quality. Understanding the relationship between the variables associated with PDF and its intensity, duration and frequency may help better understand the underlying mechanisms of this burdensome condition.

Background: Little is known about the underlying aetiology of fatigue in haemodialysis (HD) patients apart from a significant association and overlapping symptomatology with depressive symptoms. Growing evidence exists for the involvement of the immune system, by pro-inflammatory cytokines, in the development of fatigue in other inflammatory diseases. In HD patients, increased exposure to bacterial endotoxins may contribute to an inflammatory response and may potentially lead to fatigue. We therefore aimed (i) to assess the interrelationship between serum endotoxin (EA) levels, interleukin-6 (IL-6) levels and fatigue in HD patients; (ii) to evaluate whether there is a relationship between depressive symptoms and inflammation as well and (iii) to what extent depressive symptoms and fatigue are related to each other. Methods: Fatigue and depressive symptoms in daily life were assessed in 59 individuals using the SF-36 vitality subscale and the Geriatric Depression Scale. Blood samples were collected on a mid-week dialysis session to determine EA levels, through the Endotoxin Activity Assay (EAATM), and IL-6 concentrations, through the commercially available Abcam ELISA (Enzyme-Linked Immunosorbent Assay) kit. Results: EA, IL-6 levels and depressive symptoms were significantly correlated with fatigue. EA levels and depressive symptoms were significant predictors of fatigue, explaining 31% of its variance. However, EA and IL-6 were not significantly associated with depression. Conclusions: Fatigue in HD patients may be related to endotoxemia and inflammation through IL-6. Furthermore, fatigue is significantly associated with depressive symptoms. Future research into the causal interrelationship of inflammation, fatigue and depression in HD patients might lead to potential targets for therapeutic strategies.

Frailty encompasses several domains (i.e., metabolic, physical, cognitive). The multisystem derangements underlying frailty pathophysiology, its phenotypic heterogeneity, and the fluctuations of individuals across severity states have hampered a comprehensive appraisal of the condition. Circulating biomarkers emerged as an alleged tool for capturing this complexity and, as proxies for organismal metabolic changes, may hold the advantages of: 1) supporting diagnosis, 2) tracking the progression, 3) assisting healthcare professionals in clinical and therapeutic decision-making, and 4) verifying the efficacy of an intervention before measurable clinical manifestations occur. Among available analytical tools, metabolomics are able to identify and quantify the (ideally) whole repertoire of small molecules in biological matrices (i.e., cells, tissues, and biological fluids). Results of metabolomics analysis may define the final output of genome-environment interactions at the individual level. This entire collection of metabolites is called “metabolome” and is highly dynamic. Here, we discuss how monitoring the dynamics of metabolic profiles may provide a read-out of the environmental and clinical disturbances affecting cell homeostasis in frailty-associated conditions.

Recently, it has been demonstrated that chronic inflammation could have a role on fatigue onset in chronic hemodialysis (HD). Research on neuro-immune interactions highlighted that an alteration of basal ganglia functioning, secondary to chronic inflammation, may translate in a reduced motivation and altered reward processes in chronic diseases. This study investigated a possible correlation between fatigue severity and reward mechanisms, that regulate motivational dispositions, in HD patients. Evaluation scales were administered to ninety-four patients on HD (54 Male, 40 Female; Mdage = 67±26.5; Dialytic Mdage in years = 4±6.3. Fatigue was assessed by using Fatigue Severity Scale (FSS). Behavioural Inhibition System (BIS) and Behavioural Activation System (BAS) Scale was administered to investigate approach/avoidance behaviours. Anxiety and depression were measured by State-Trait Anxiety Inventory (STAI-Y) and Beck Depression Inventory (BDI-II). Results show that the distribution of HD patients for FSS score did not show a normal pattern. FSS score was significantly higher in patients with high BIS Z-score than in patients with low and medium BIS Z-score. BDI score and STAI-Y scores were similar among BIS Z-score groups of patients. Findings suggest that in patients on chronic hemodialysis there is a correlation between fatigue severity symptoms and motivational disposition mechanisms that predispose to action inhibition.

Health-related quality of life (HRQOL) in patients on chronic hemodialysis has not improved significantly in the last 20 years. This is largely due to their substantial symptom burden which is rarely assessed and treated in routine clinical practice. This is also consequence of the lack of an appropriate armamentarium for the treatments of such symptoms. Adequate studies on the causes and pathogenesis of the symptoms of hemodialysis patients are needed followed by high-quality studies on possible therapeutic pharmacological and non-pharmacological interventions. Patients on chronic hemodialysis deserve a better quality of life.

Context: Fatigue is one of the most prevalent symptoms among hemodialysis (HD) patients. To design effective treatments, it is crucial to understand the diurnal pattern of fatigue in this population. Objectives: The objectives of this study were to assess diurnal changes in fatigue in patients undergoing hemodialysis and their relation with depressive symptoms and to explore whether fatigue may become a classically conditioned response to the hospital environment. Methods: A prospective, observational study was conducted in 51 HD patients. Subjects repeatedly rated their current fatigue on three different days during one week of hemodialysis treatment to capture changes in momentary fatigue. First, on an HD treatment day, fatigue was measured one hour before and immediately before dialysis, as well as immediately after dialysis and again at 22:00 PM Second, on the postdialysis day and on the seventh weekday (when patients had not received treatment on the previous day), fatigue was measured at the same moments in time as the two measurements before dialysis on the treatment day. Beck Depression Inventory-II and Fatigue Severity Scale were administered to evaluate depressive mood and fatigue severity in daily life. Results: Fatigue increased as a result of hemodialysis treatment over the entire sample. However, diurnal fatigue patterns differed significantly between individuals high and low in depressive symptoms, with the former being fatigued more constantly throughout the day, and the latter experiencing increases in fatigue due to treatment. Pretreatment fatigue experienced in the hospital environment followed a pattern consistent with the development of a classically conditioned response. Conclusion: Diurnal fatigue patterns during hemodialysis treatment are associated with depressive symptoms, and classical conditioning may play a role in the experience of pretreatment fatigue.

Xerostomia, or dryness of oral cavity, is relatively common in patients on chronic hemodialysis and significantly impairs their quality of life. Xerostomia is often the consequence of reduced salivary flow resulting from atrophy and fibrosis of the salivary glands, an event that is of uncertain origin. Many medications commonly used in dialysis patients may also cause or exacerbate xerostomia. Its consequences may be serious and disturbing and include difficulties in chewing, swallowing, tasting, and speaking; increased risk of oral disease, including lesions of the mucosa, gingiva and tongue; bacterial and fungal infections, such as candidiasis, dental caries, and periodontal disease; interdialytic weight gain resulting from increased fluid intake; and a reduction in the quality of life. Therapeutically, stimulation of the salivary glands to increase the production of saliva mechanically by chewing-gum, mouthwash, acupressure, or transcutaneous electrical stimulation has had modest success. However, the long-term effectiveness of such treatments still needs to be investigated and defined. Xerostomia remains a frustrating and disturbing symptom for patients on hemodialysis. Further efforts should be made to find the causes and the mechanisms of the reduced salivary flow observed in patients on chronic hemodialysis.

Introduction: The present study aimed to determine the variables that are associated with a longer dialysis recovery time (DRT) and to define the relationship that exists between DRT and the ultrafiltration rate (UFR) in prevalent chronic hemodialysis (CHD) patients. Methods: We studied 210 prevalent CHD of 5 hemodialysis units in Central Italy. Patients were invited to answer to the question: “How long does it take you to recover from a dialysis session?” Answers to this question were subsequently converted into minutes. Demographic, clinical and laboratory parameters were recorded for each patient as well as the UFR (mL/kg/h), the dialysate sodium concentration and temperature. Results: Median DRT was 180 min (60–420). Ninety five (45%) patients had a DRT ≥ the median value. Mean UFR was 9.2 ± 3.0 mL/kg/h. Patients with a lower DRT had a less prevalent disability in the instrumental activities daily living, had a higher UFR, and a lower dialysate temperature, as compared with subjects with higher DRT. According to the logistic regression model, UFR was associated with a DRT below the median (i.e., 180) in the unadjusted model (OR 1.12; 95% CI 1.02–1.23; p = 0.019), after adjusting for age and sex (OR 1.11; 95% CI 1.01– 1.22; p = 0.025), and in the fully adjusted model (OR 1.11; 95% CI 1.04–1.22; p = 0.040). UFR increase was associated with increasing probability of DRT below the median (p for trend= 0.035). The highest tertile of DRT was associated with UFR below the mean value (i.e., 9.2 mL/kg/h) in multinomial logistic regression having the lowest DRT tertile as reference. DRT was significantly lower in patients with UFR >13 mL/ kg/h than in patients with UFR 10–13 or <10 mL/kg/h. Conclusion: DRT is inversely associated with UFR in CHD patients. Whether a high UFR should be recommended to reduce the DRT needs to be elucidated through an adequate prospective randomized study.

Mitochondrial structural and functional integrity is maintained through the coordination of several processes (e.g., biogenesis, dynamics, mitophagy), collectively referred to as mitochondrial quality control (MQC). Dysfunctional MQC and inflammation are hallmarks of aging and are involved in the pathogenesis of muscle wasting disorders, including sarcopenia and cachexia. One of the consequences of failing MQC is the release of mitochondria-derived damage-associated molecular patterns (DAMPs). By virtue of their bacterial ancestry, these molecules can trigger an inflammatory response by interacting with receptors similar to those involved in pathogen-associated responses. Mitochondria-derived DAMPs, especially cell-free mitochondrial DNA, have recently been associated with conditions characterized by chronic inflammation, such as aging and degenerative diseases. Yet, their actual implication in the aging process and muscle wasting disorders is at an early stage of investigation. Here, we review the contribution of mitochondria-derived DAMPs to age-related systemic inflammation. We also provide arguments in support of the exploitation of such signaling pathways for the management of muscle wasting conditions.

Sarcopenia is a well-known geriatric syndrome that has been endorsed over the years as a biomarker allowing for the discrimination, at a clinical level, of biological from chronological age. Multiple candidate mechanisms have been linked to muscle degeneration during sarcopenia. Among them, there is wide consensus on the central role played by the loss of mitochondrial integrity in myocytes, secondary to dysfunctional quality control mechanisms. Indeed, mitochondria establish direct or indirect contacts with other cellular components (e.g. endoplasmic reticulum, peroxisomes, lysosomes/vacuoles) as well as the extracellular environment through the release of several biomolecules. The functional implications of these interactions in the context of muscle physiology and sarcopenia are not yet fully appreciated and represent a promising area of investigation. Here, we present an overview of recent findings concerning the interrelation between mitochondrial quality control processes, inflammation and the metabolic regulation of muscle mass in the pathogenesis of sarcopenia highlighting those pathways that may be exploited for developing preventive and therapeutic interventions against muscle aging.

Background: Functional impairment is associated with adverse outcomes in older people, as well as in patients on chronic hemodialysis. The aim of this study was to evaluate if functional impairment represents a risk factor for reduced survival in patients on chronic hemodialysis. Methods: All incident chronic hemodialysis patients of Lazio, a large region of central Italy, registered in the Dialysis and Transplant Lazio Region Registry (DTLRR) in the period 2008–2013 were considered eligible. Inclusion criteria were: age > 18 years, resident in Lazio, still doing dialysis after 90 days from incidence date, doing hemodialysis or hemodiafiltration treatment for > 9 h/week. Patients were stratified into three classes of functional activity: total autonomy, autonomy in some activities, and not self-sufficient. Functional activity was assessed for each patient by the referring physician for the DTLRR from the ~ 90 hemodialysis units of the Lazio region. Each patient was followed from date of first dialysis treatment to the end of the study (31/12/2015) or death or renal transplant, whichever occurred first. Cox proportional hazard models were performed to obtain mortality hazard ratios (HR), 95% confidence intervals (CI), for each class of functional activity adjusting for sex, age, country of birth, city of residence, body mass index (BMI), type of nephropathy, vascular access, previous nephrology counselling, weekly hours of hemodialysis, serum albumin, hemoglobin, and presence of comorbidities (e.g. vascular diseases, coronary disease, and diabetes). Results: A total of 3356 patients were studied. In the whole follow-up period, 1622 deaths occurred (48%). Functional impairment was associated with the risk of mortality: compared to ‘total autonomy’, the HR for ‘autonomy in some activities’ was 1.30 [95% CI: 1.14–1.49] and for ‘not self-sufficient’ 1.71 [1.47–1.99] (p for trend < 0.05). The number of evitable deaths attributable to reduced functional

Sarcopenia, the progressive and generalised loss of muscle mass and strength/function, is a major health issue in older adults given its high prevalence and burdensome clinical implications. Over the years, this condition has been endorsed as a marker for discriminating biological from chronological age. However, the absence of a unified operational definition has hampered its full appreciation by healthcare providers, researchers and policy-makers. In addition to this unsolved debate, the complexity of musculoskeletal ageing represents a major challenge to the identification of clinically meaningful biomarkers. Here, we illustrate the advantages of biomarker discovery procedures in muscle ageing based on multivariate methodologies as an alternative approach to traditional single-marker strategies. The rationale, design and methods of the “BIOmarkers associated with Sarcopenia and PHysical frailty in EldeRly pErsons” (BIOSPHERE) study are described as an application of a multi-marker strategy for the development of biomarkers for the newly operationalised Physical Frailty & Sarcopenia condition.

Mitochondrial dysfunction is a relevant mechanism in cardiac aging. Here, we investigated the effects of late-life enalapril administration at a non-antihypertensive dose on mitochondrial genomic stability, oxidative damage, and mitochondrial quality control (MQC) signaling in the hearts of aged rats. The protein expression of selected mediators (i.e., mitochondrial antioxidant enzymes, energy metabolism, mitochondrial biogenesis, dynamics, and autophagy) was measured in old rats randomly assigned to receive enalapril (n = 8) or placebo (n = 8) from 24 to 27 months of age. We also assessed mitochondrial DNA (mtDNA) content, citrate synthase activity, oxidative lesions to protein and mtDNA (i.e., carbonyls and the abundance of mtDNA 4834 deletion), and the mitochondrial transcription factor A (TFAM) binding to specific mtDNA regions. Enalapril attenuated cardiac hypertrophy and oxidative stress-derived damage (mtDNA oxidation, mtDNA 4834 deletion, and protein carbonylation), while increasing mitochondrial antioxidant defenses. The binding of mitochondrial transcription factor A to mtDNA regions involved in replication and deletion generation was enhanced following enalapril administration. Increased mitochondrial mass as well as mitochondriogenesis and autophagy signaling were found in enalapril-treated rats. Late-life enalapril administration mitigates age-dependent cardiac hypertrophy and oxidative damage, while increasing mitochondrial mass and modulating MQC signaling. Further analyses are needed to conclusively establish whether enalapril may offer cardioprotection during aging.

Introduction We evaluated the gene expression levels of atrogin-1, MuRF1, myostatin, follistatin, activin A, and inhibin alpha in skeletal muscle samples of patients with gastric cancer and controls. Methods We studied 38 cancer patients and 12 controls who underwent surgery for gastric adenocarcinoma and benign abdominal diseases, respectively. A biopsy specimen was obtained from the rectus abdominis muscle from all participants. The relative gene expression of atrogin-1, MuRF1, myostatin, follistatin, activin A, and inhibin alpha was determined by qRT-PCR analysis. Results Atrogin-1 and MuRF1 mRNA expression was similar between cancer patients and controls and was unaffected by the disease stage or the severity of body weight loss. Transcript levels of myostatin and follistatin did not differ between cases and controls and were similar across disease stages and categories of weight loss. Finally, no differences were detected in activin A and inhibin alpha gene expression between cancer patients and controls. Discussion In skeletal muscle, the gene expression of atrogin-1, MuRF1, myostatin, follistatin, activin A, and inhibin alpha is not affected by the presence of cancer. The expression of atrophy-related genes is unaffected by the disease stage and the degree of weight loss. © 2013 Wiley Periodicals, Inc.

Health-related quality of life (HRQOL) in patients on chronic hemodialysis has not improved significantly in the last 20 years. This is largely due to their substantial symptom burden which is rarely assessed and treated in routine clinical practice. It also is a consequence of the lack of an appropriate armamentarium for the treatments of such symptoms. Adequate studies on the causes and pathogenesis of the symptoms of hemodialysis patients are needed followed by high quality studies on possible therapeutic pharmacological and nonpharmacological interventions.

OBJECTIVE: To retrospectively compare the clinical outcomes of percutaneous cholecystostomy (PC) and cholecystectomy in patients with acute cholecystitis admitted to an urban University Hospital.PATIENTS AND METHODS: We studied 646 patients with acute cholecystitis. Ninety patients had placement of a PC at their index hospitalization, and 556 underwent cholecystectomy. Of the 90 patients with PC, 13 underwent subsequent elective cholecystectomy.RESULTS: Overall, in-hospital mortality and postoperative complications were significantly higher in patients who received PC than in those who underwent cholecystectomy. In the ASA score 1-2 group, patients with PC were significantly older and had a longer postoperative stay while their mortality and morbidity were similar to patients who underwent cholecystectomy. In patients with ASA score of 3, PC and cholecystectomy did not differ significantly for demographic variables and clinical outcomes such as hospital stay, in-hospital mortality, postoperative complications and distribution of complications according to the classification of Clavien-Dildo. In mild, moderate, and severe cholecystitis, patients who underwent PC were significantly older than those who received cholecystectomy. In general, in mild, moderate and severe cholecystitis, the clinical outcomes did not differ significantly between patients who received PC and cholecystectomy. Morbidity was higher in patients with mild cholecystitis who underwent PC. Of the 77 patients dismissed from the hospital with drainage, 12 (15.6%) developed biliary complications and 5 needed substitutions of the drainage itself.CONCLUSIONS: PC does not offer advantages compared to cholecystectomy in the treatment of acute cholecystitis. Its routine use is therefore questioned. There is need of an adequate, randomized study that compares PC and cholecystectomy in high-risk patients with moderate-severe cholecystitis.

PURPOSE: Fatigue is common in end-stage renal disease patients receiving hemodialysis, reduces significantly their quality of life and is associated with all-cause and cardiac-related mortality. Unfortunately, little is known about the course of fatigue in patients on chronic hemodialysis. METHODS: The Vitality Subscale of the SF-36 (SF-36 VS), Short-Form Health Survey, was administered to 45 patients in January (T1), June (T2) and November (T3) 2015. RESULTS: The score of the SF-36 VS did not differ significantly among T1, T2 and T3. Similarly, the 1-year course of the SF-36 Vitality Subscale score did not differ significantly among T1, T2 and T3 after stratification of patients for sex, age, BMI, IADL and Charlson. Between T1 and T2, 21 out of 45 patients (46.6%) changed their fatigue status: 8 fatigued patients became not-fatigued and 13 not-fatigued patients became fatigued. Between T2 and T3, 12 out of 45 (26.6%) patients changed their fatigue status: 5 fatigued patients became not-fatigued and 7 not-fatigued patients became fatigued. Between T1 and T3, 19 out of 45 patients (42.2%) changed their fatigue status: 6 fatigued patients became not-fatigued and 13 not-fatigued became fatigued. CONCLUSION: The present study is the first to identify variations in fatigue status among patients on chronic hemodialysis during 1-year course. These findings suggest to frequently assess the presence and severity of fatigue in patients on chronic hemodialysis.

Experimental studies have suggested that defective skeletal muscle regeneration could contribute to muscle wasting in cancer patients. However, data in humans are still lacking. In this study we aimed to assess the expression of the genes involved in muscle regeneration in gastric cancer patients. The RNA expression of the genes involved in muscle regeneration was assessed in the rectus abdominis muscle of patients with gastric cancer (n=30) and in age-matched control subjects (n=8). The Pax7 expression was significantly increased in the muscle of gastric cancer patients, either in the first stages of the disease or in stages IIIA and B. The increased expression was present both in stages IA and B and in stages II and III. The MyoD espression was also higher in the cancer patients than in the controls. However, the increased MyoD expression was present only in stages IA and B and not in the more advanced stages of the disease. The Myf5 expression, as well as that of the neonatal isoform of Myosin Heavy Chain (nMHC) did not differ significantly between the cancer patients and the controls. The necdin expression was negligible in healthy adult muscles and was significantly up-regulated in the muscle of gastric cancer patients. Its expression was highly increased in stages IA and B while it was similar to the control in stages II and III. The results of the present study show that in the skeletal muscle of gastric cancer patients, the expression of the genes involved in muscle regeneration is increased with respect to the controls.

Experimental studies have suggested that defective skeletal muscle regeneration could contribute to muscle wasting in cancer patients. However, data in humans are still lacking. In this study we aimed to assess the expression of the genes involved in muscle regeneration in gastric cancer patients. The RNA expression of the genes involved in muscle regeneration was assessed in the rectus abdominis muscle of patients with gastric cancer (n=30) and in age-matched control subjects (n=8). The Pax7 expression was significantly increased in the muscle of gastric cancer patients, either in the first stages of the disease or in stages IIIA and B. The increased expression was present both in stages IA and B and in stages II and III. The MyoD espression was also higher in the cancer patients than in the controls. However, the increased MyoD expression was present only in stages IA and B and not in the more advanced stages of the disease. The Myf5 expression, as well as that of the neonatal isoform of Myosin Heavy Chain (nMHC) did not differ significantly between the cancer patients and the controls. The necdin expression was negligible in healthy adult muscles and was significantly up-regulated in the muscle of gastric cancer patients. Its expression was highly increased in stages IA and B while it was similar to the control in stages II and III. The results of the present study show that in the skeletal muscle of gastric cancer patients, the expression of the genes involved in muscle regeneration is increased with respect to the controls.

Muscle wasting is the most important phenotypic and clinical feature of cancer cachexia, and the principal cause of impaired physical function, fatigue, and respiratory complications. Muscle loss has been attributed to a variable combination of reduced nutritional intake and an imbalance between anabolic and catabolic processes. It has been suggested that defective skeletal muscle regeneration may also contribute to muscle wasting in cancer patients. However, there is little invitro or invivo data available, in either animals or in humans, regarding skeletal muscle regeneration in cancer wasting. The aim of the present review is to define the role of skeletal muscle regeneration in the muscle wasting of cancer patients and to determine possible therapeutic implications.