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The present cross-sectional study aimed to compare the prevalence, the characteristics of post-dialysis fatigue and the length of recovery time after hemodialysis in prevalent end-stage renal disease patients (ESRD) receiving bicarbonate hemodialysis (HD) or hemodiafiltration (HDF).Patients were suffering from post-dialysis fatigue if they spontaneously offered this complaint when asked the open-ended question: "Do you feel fatigued after dialysis?". Moreover, each patient was invited to rate the intensity, duration, and frequency of post-dialysis fatigue from 1 to 5. In order to assess RECOVERY TIME AFTER DIALYSIS, patients were invited to answer to the following single open-ended question: "How long does it take you to recover from a dialysis session?"We included 335 patients: 252 received HD and 83 received HDF. Post-dialysis fatigue was present in 204 patients (60.9%). Prevalence of post-dialysis fatigue did not differ significantly between patients on HD (62.3%) and on HDF (56.6%; p = 0.430). Median recovery time after dialysis was 180 min [180-240] and did not differ significantly between the two subgroups (180 min [130-240] and 240 min [120-332] p = 0.671, respectively). Median post-dialysis fatigue intensity, duration, and frequency were 3 [1-5], 3 [1-5], and 4 [1-5] and did not differ significantly between patients on HD and on HDF. At the multivariate analysis, age, ADL and hemoglobin levels were the independent predictors of the HDF treatment.Prevalence and characteristics of post-dialysis fatigue do not differ significantly between patients receiving bicarbonate HD or HDF.

Patients with head and neck cancer (HNC) are frequently malnourished at the time of diagnosis and before beginning treatment. In addition, chemoradiotherapy causes or exacerbates symptoms such as alteration or loss of taste, mucositis, xerostomia, fatigue, nausea, and vomiting, with consequent worsening of malnutrition. If obstructing cancer and/or mucositis interferes with swallowing, enteral nutrition should be delivered by a nasogastric tube (NGT) or percutaneous endoscopic gastrostomy (PEG). To review studies comparing NGT's and PEG's nutrition outcomes, survival, hospitalizations, radiotherapy interruptions, quality of life, and swallowing function. Two hundred fifty publications were identified via electronic databases. 26 manuscripts that met the inclusion criteria were included for analysis. We divided the analysis in two sections: (1) comparison of enteral nutrition through NGT or PEG and (2) comparison of reactive PEG (R-PEG) and prophylactic PEG (P-PEG). They have comparable nutrition outcomes, number of radiotherapy interruptions, survival, and quality of life, whereas swallow function seems better with NGT. PEG may be associated with major complications such as exit-site infection, malfunction, leakage, pain, pulmonary infection, and higher costs. Nevertheless, NGTs dislodged more often; patients find NGTs more inconvenient; NGTs may cause aspiration pneumonia; P-PEG and R-PEG have similar nutrition outcomes, number of radiotherapy interruptions, and survival. PEG does not have better nutrition, oncologic, and quality-of-life outcomes than NGT. Prophylactic feeding through NGT or PEG, compared with reactive feeding, does not offer significant advantages in nutrition outcomes, radiotherapy interruptions, and survival. However, the number of prospective randomized studies on this topic is limited; consequently, definitive conclusions cannot be drawn. Further adequate, prospective randomized studies are needed.

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.

Aim of the present study was to assess whether post-dialysis fatigue (PDF) may be related to pre- or post-dialysis levels of serum S100B protein. Hemodialysis patients (HD) who answered to be fatigued after their hemodialysis sessions when asked: "Do you feel worse after dialysis? if they answered yes" were considered to suffer from PDF. Serum Interleukins (IL-1β, IL-6, IL-10), TNF-α and S100B were assessed by ELISA kit.Thirty HD patients were studied: 22 (73.4%) reported to suffer from PDF. Serum S100B post-dialysis levels (median [IQR] = 17.4 μg [7.1 to 30.9]) were significantly higher than serum S100B pre-dialysis levels (median [IQR] = 5 μg [1.4 to 22.1]; p = 0.0001). S100B post-dialysis was significantly higher than S100B pre-dialysis either in patients with PDF or without PDF.Pre- and post-dialysis values of serum S100B and its delta did not differ significantly between patients with and without PDF and were not associated with the length of the TIRD in patients on chronic hemodialysis.

Background: The factors associated with the inability to start hemodialysis with an arteriovenous fistula (AVF) in chronic kidney disease patients are not fully understood. Aim: Evaluating factors associated with type of vascular access at the first chronic hemodialysis and at 1 year after it. Methods: The study cohort includes patients registered in the Regional Dialysis and Transplant Registry of Lazio undergoing first hemodialysis between 2008 and 2015. Logistic regression models were used to evaluate the association between socio-demographic, clinical and care/organizational factors, and vascular access at first hemodialysis. Cox regression models were used to assess the odds of switching to AVF during the first year of hemodialysis among patients starting dialysis with central venous catheter (CVC). Results: In the cohort of 6208 incident hemodialysis patients, 52.7% had an AVF and 47.3% had a CVC. Among the 2939 incident patients with CVC, 27.4% switched to FAV after 1 year. A higher probability of starting dialysis with AVF was observed among males (OR = 1.83; 95% CI 1.63–2.06), while a lower probability was observed among patients aged >85 years (OR 0.64; IC 95% 0.51–0.80). Patients with early referral to a nephrologist had a triple probability of start dialysis with AVF. We observed a higher odds of switch to AVF among males (HR = 1.62; 95% CI 1.40–1.89) and a lower odds among patients over 65 years. Conclusion: The observed high rate of AVF at the start of hemodialysis and of the switch from CVC to AVF in the first year, although declining since 2008, is a positive outcome. However, over one-third of patients maintain the CVC as vascular access for the first year because of unmodifiable factors, such as gender, age, comorbidity. The present study suggests that logistics/management and assistance/welfare problems may contribute to the delay or lack of AVF placement in incident hemodialysis patients or within the first year of dialysis.

Background Fatigue in haemodialysis (HD) patients is a prevalent but complex symptom impacted by biological, behavioural, psychological and social variables. Conventional retrospective fatigue questionnaires cannot provide detailed insights into symptom variability in daily life and related factors. The experience sampling methodology (ESM) overcomes these limitations through repeated momentary assessments in patients’ natural environments using digital questionnaires. This study aimed to gain in-depth understanding of HD patients’ diurnal fatigue patterns and related variables using a mobile Health (mHealth) ESM application and sought to better understand the nature of their interrelationships. Methods Forty HD patients used the mHealth ESM application for 7 days to assess momentary fatigue and potentially related variables, including daily activities, self-reported physical activity, social company, location and mood. Results Multilevel regression analyses of momentary observations (n = 1777) revealed that fatigue varied between and within individuals. Fatigue was significantly related to HD treatment days, type of daily activity, mood and sleep quality. Time-lagged analyses showed that HD predicted higher fatigue scores at a later time point (β = 0.22, P = 0.013). Interestingly, higher momentary fatigue also significantly predicted more depressed feelings at a later time point (β = 0.05, P = 0.019) but not the other way around. Conclusions ESM offers novel insights into fatigue in chronic HD patients by capturing informative symptom variability in the flow of daily life. Electronic ESM as a clinical application may help us better understand fatigue in HD patients by providing personalized information about its course and relationship with other variables in daily life, paving the way towards personalized interventions.

Dopaminergic nigrostriatal denervation and widespread intracellular α-synuclein accumulation are neuropathologic hallmarks of Parkinson’s disease (PD). A constellation of peripheral processes, including metabolic and inflammatory changes, are thought to contribute to neurodegeneration. In the present study, we sought to obtain insight into the multifaceted pathophysiology of PD through the application of a multi-marker discovery approach. Fifty older adults aged 70+, 20 with PD and 30 age-matched controls were enrolled as part of the EXosomes in PArkiNson Disease (EXPAND) study. A panel of 68 circulating mediators of inflammation, neurogenesis and neural plasticity, and amino acid metabolism was assayed. Biomarker selection was accomplished through sequential and orthogonalized covariance selection (SO-CovSel), a multi-platform regression method developed to handle highly correlated variables organized in multi-block datasets. The SO-CovSel model with the best prediction ability using the smallest number of variables was built with seven biomolecules. The model allowed correct classification of 94.2 ± 3.1% participants with PD and 100% controls. The biomarker profile of older adults with PD was defined by higher circulating levels of interleukin (IL) 8, macrophage inflammatory protein (MIP)-1β, phosphoethanolamine, and proline, and by lower concentrations of citrulline, IL9, and MIP-1α. Our innovative approach allowed identifying and evaluating the classification performance of a set of potential biomarkers for PD in older adults. Future studies are warranted to establish whether these biomolecules could serve as biomarkers for PD as well as unveil new targets for interventions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11357-020-00192-2) contains supplementary material, which is available to authorized users.

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

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 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 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. Graphical abstract

This study explores the link between fatigue and apathy in patients on chronic hemodialysis (HD).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).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.Future longitudinal studies could determine if apathy is a causative factor for fatigue manifestation and development in HD patients.

Fatigue is a commonly reported and debilitating symptom among patients with CKD, yet little is known about its epidemiology, pathogenesis, and treatment. Various measurement tools have been used in published studies to identify and quantify fatigue. These include several single-item measures embedded in longer questionnaires for assessing depression, quality of life, or symptom burden in patients with kidney disease. Approximately 70% of patients with CKD report fatigue, with up to 25% reporting severe symptoms. Patient-reported fatigue is associated with death, dialysis initiation, and hospitalization among individuals with CKD. The pathophysiology is multifactorial and likely includes decreased oxygen delivery and increased reliance on anaerobic metabolism, thus generating lactic acidosis in response to exertion; the effects of chronic metabolic acidosis and hyperphosphatemia on skeletal muscle myocytes; protein-energy wasting and sarcopenia; and depression. Physical activity has been shown to improve fatigue in some small but promising trials, and so should be recommended, given the additional benefits of exercise. Targeting higher hemoglobin levels with erythropoiesis-stimulating agents may improve fatigue, but potential adverse cardiovascular effects preclude their use to solely treat fatigue without the presence of another indication. Current guidelines recommend cautious individualization of hemoglobin targets for those at low cardiovascular risk who still experience fatigue or functional limitation despite a hemoglobin level of 10 g/dl. Sodium bicarbonate supplementation for the treatment of metabolic acidosis may also improve functional status. Selective serotonin reuptake inhibitors have not been consistently shown to improve fatigue in patients with kidney disease, but an ongoing trial will evaluate the effect of alternative antidepressant drug and behavioral activation therapy on fatigue in patients with CKD. Overall, more research is needed to further clarify underlying mechanisms of fatigue and identify effective, targeted treatments for patients with CKD.

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; Md

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.

(1) Background: Interest in gender disparities in epidemiology, clinical features, prognosis and health care in chronic kidney disease patients is increasing. Aims of the study were to evaluate the association between gender and vascular access (arteriovenous fistula (AVF) or central venous catheter (CVC)) used at the start of hemodialysis (HD) and to investigate the association between gender and 1-year mortality. (2) Methods: The study includes 9068 adult chronic HD patients (64.7% males) registered in the Lazio Regional Dialysis Register (Jan 2008–Dec 2018). Multivariable logistic regression models were used to investigate the associations between gender and type of vascular access (AVF vs. CVC) and between gender and 1-year mortality. Interactions between gender and socio-demographic and clinical variables were tested adding the interaction terms in the final model. (3) Results: Females were older, had lower educational level and lower rate of self-sufficiency compared to males. Overall, CVC was used in 51.2% of patients. Females were less likely to use AVF for HD initiation than males. 1354 out of 8215 (16.5%) individuals died at the end of the follow-up period. Interaction term between gender and vascular access was significant in the adjusted model. From stratified analyses by vascular access, OR female vs. male (AVF) = 0.65, 95% CI 0.48–0.87 and OR female vs. male (CVC) = 0.88, 95% CI 0.75–1.04 were found. (4) Conclusion: This prospective population-based cohort study in a large Italian Region showed that in females starting chronic HD AVF was less common respect to men. The better 1-year survival of females is more evident among those women with AVF. Reducing gender disparity in access to AVF represents a key point in the management of HD patients.

Background and Aims Fatigue is one of the most prioritized outcomes among haemodialyis (HD) patients with great impact on health-related quality of life. However, evidence-based therapies are lacking. A better understanding of fatigue symptoms and related behavioral, social and psychological factors in HD patients is of primary importance. Conventionally used fatigue measurement instruments, such as the Fatigue Severity Scale (FSS), only provide a general picture of fatigue severity and are prone to memory bias due to their retrospective nature. However, they cannot provide detailed insight in diurnal variations in fatigue and related factors in daily life. The Experience Sampling Methodology (ESM) overcomes these limitations by repeated “real-time” assessments in patients’ natural environments using digital questionnaires. The aims of this study were (i) to gain in-depth understanding of HD patients’ diurnal fatigue patterns and related variables using a mobile Health (mHealth) ESM application, (ii) to better understand the nature of their interrelationships, and (iii) to explore the relationship between real-time experience of fatigue and its retrospective assessment. Method Forty chronic HD patients used the mHealth ESM application for seven consecutive days to assess momentary fatigue and potentially related variables, including daily activities, self-reported physical activity, social company, location and mood patterns. In addition, patients retrospectively evaluated their fatigue experience over the preceding day and week by means of end-of-day, and end-of-week questionnaires and the FSS. Results Multilevel regression analyses of momentary observations (N=1778) revealed that fatigue varied between and within individuals (Fig.1). Fatigue was significantly related to type of daily activity and mood. Time-lagged analyses showed that HD treatment predicted higher fatigue scores at a later time point, β = 0.22, p = 0.013. Interestingly, higher momentary fatigue also significantly predicted more depressed feelings at a later time point, β = 0.05, p = 0.019, but not the other way around. Retrospective evaluation of fatigue experience over the preceding week was significantly higher than the average of momentary fatigue scores, t(38) = 3.54, p = 0.001. The FSS correlated moderately with the average of momentary fatigue scores, r = 0.63. Conclusion This study demonstrates diurnal variability of fatigue in chronic HD patients. It also corroborates a previous result from our research group showing that fatigue increases as a response to HD treatment (i.e. post-dialysis fatigue) and should, at least partially, be distinguished from a more general fatigue experience. Furthermore, our findings may suggest that depressed mood is secondary to fatigue in HD patients given their temporal relationship. Finally, retrospective fatigue assessment led to overestimation of the real-time fatigue experience. ESM offers novel insights in fatigue in HD patients by capturing informative symptom variability in the flow of daily life, which is not provided by conventional fatigue measures. Moreover, ESM provides personalized information about fatigue symptoms and their relationship with other variables in daily life, paving the way towards personalized interventions for HD patients.

Background: The aetiology of postdialysis fatigue (PDF), an intermittent but debilitating fatigue occurring after haemodialysis (HD) treatment, is still unclear. In other inflammatory diseases, increasing evidence points toward the involvement of the immune system in the onset of fatigue symptoms. Altered serum levels of inflammatory cytokines have also been shown in HD patients. Therefore, we investigated whether pre- and postdialysis serum levels of pro- and anti-inflammatory cytokines (i.e. IL-1β, IL-6, TNF-α and IL-10) or their intradialytic changes (if any) were related to PDF or the time HD patients reported needing to recover from HD treatment (TIRD). Methods: Serum levels of IL-1β, IL-6, TNF-α and IL-10 were measured immediately before and after HD in 45 patients using commercially available kits on an ELLA™ automated immunoassay system. The presence and severity of PDF as well as TIRD duration were assessed by self-report measures. Key results: Seventy-four percent of patients reported PDF, with a median PDF severity index of 3.30 [IQR: 3.00–4.30] on a scale from 1 to 5. Median TIRD was 120 min [IQR: 60–480]. PDF severity correlated strongly with TIRD, rs = 0.85, p < 0.001. Only predialysis levels of IL-10 significantly and positively correlated with PDF severity (rs = 0.43, p = 0.003). Conclusion: Findings of the present study do not support the involvement of the immune system in the onset of PDF or the time patients needed to recover from HD treatment. A positive, but counterintuitive relationship was found between predialysis levels of anti-inflammatory IL-10 and PDF severity, which warrants further research.

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.

Context Fatigue is prevalent among hemodialysis (HD) patients and associated with depressive mood. To advance our understanding of its etiology and develop appropriate treatments, reliable measurement instruments are needed. However, conventional fatigue and mood questionnaires are prone to bias because of their retrospective nature and may misrepresent or overestimate actual symptom experience (i.e., the so-called memory-experience gap). Experience sampling methodology (ESM) overcomes this limitation through repeated real-time assessments in patients' natural environment, thereby providing reliable and ecologically valid data. Objectives We investigated to what extent retrospective symptom reporting accurately represents real-time experiences of fatigue and mood in HD patients using an ESM mobile Health application (PsyMate™; smartHealth GmbH, Luxembourg). Methods Forty HD patients used the PsyMate for one week to assess real-time fatigue and mood. In addition, they retrospectively evaluated their symptom experience completing end-of-day and end-of-week questionnaires as well as the conventional Fatigue Severity Scale and Hospital Anxiety and Depression Scale. Results Results of real-time observations (N = 1777) showed that fatigue and mood varied between and within individuals. Retrospective end-of-week fatigue evaluation was significantly higher than the average real-time fatigue score; t(38) = 3.54, P = 0.001, and d = 0.57. Fatigue Severity Scale and Hospital Anxiety and Depression Scale correlated moderately to strong with the average ESM score for fatigue and mood: r = 0.66 and r = 0.77, respectively. Conclusion Retrospective fatigue assessment may lead to overestimation of real-time symptom experience. ESM provides detailed insight and personalized information about symptom experiences, which may be crucial for the design of more targeted and personalized interventions for fatigue and mood problems in HD 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 SenseWear™ 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 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.

BACKGROUND It is still unknown whether ERAS program is safe, feasible and effective in elderly patients undergoing laparoscopic colorectal surgery. In addition, the definition of the "old patient" in terms of age varies across the studies and different age cut-off, such as 65, 70, and 75 years have been used worldwide. METHODS All adult patients undergoing primary, elective colorectal laparoscopic surgery between January 2017 and December 2018 were considered eligible to follow the ERAS protocol according to the Enhanced Recovery After Surgery (ERAS) Society guidelines. Elderly were defined according three different cut-off values

Physical frailty and sarcopenia (PF&S) is a prototypical geriatric condition characterized by reduced physical function and low muscle mass. The aim of the present study was to provide an initial selection of biomarkers for PF&S using a novel multivariate analytic strategy. Two-hundred community-dwellers, 100 with PF&S and 100 non-physically frail, non-sarcopenic (nonPF&S) controls aged 70 and older were enrolled as part of the BIOmarkers associated with Sarcopenia and Physical frailty in EldeRly pErsons (BIOSPHERE) study. A panel of 74 serum analytes involved in inflammation, muscle growth and remodeling, neuromuscular junction damage, and amino acid metabolism was assayed. Biomarker selection was accomplished through sequential and orthogonalized covariance selection (SO-CovSel) analysis. Separate SO-CovSel models were constructed for the whole study population and for the two genders. The model with the best prediction ability obtained with the smallest number of variables was built using seven biomolecules. This model allowed correct classification of 80.6 ± 5.3% PF&S participants and 79.9 ± 5.1% nonPF&S controls. The PF&S biomarker profile was characterized by higher serum levels of asparagine, aspartic acid, and citrulline. Higher serum concentrations of platelet-derived growth factor BB, heat shock protein 72 (Hsp72), myeloperoxidase, and α-aminobutyric acid defined the profile of nonPF&S participants. Gender-specific SO-CovSel models identified a “core” biomarker profile of PF&S, characterized by higher serum levels of aspartic acid and Hsp72 and lower concentrations of macrophage inflammatory protein 1β, with peculiar signatures in men and women. SO-CovSel analysis allowed identifying a set of potential biomarkers for PF&S. The adoption of such an innovative multivariate approach could help address the complex pathophysiology of PF&S, translate biomarker discovery from bench to bedside, and unveil novel targets for interventions.

Mitochondria are intracellular organelles involved in a myriad of activities. To safeguard their vital functions, mitochondrial quality control (MQC) systems are in place to support organelle plasticity as well as physical and functional connections with other cellular compartments. In particular, mitochondrial interactions with the endosomal compartment support the shuttle of ions and metabolites across organelles, while those with lysosomes ensure the recycling of obsolete materials. The extrusion of mitochondrial components via the generation and release of mitochondrial-derived vesicles (MDVs) has recently been described. MDV trafficking is now included among MQC pathways, possibly operating via mitochondrial–lysosomal contacts. Since mitochondrial dysfunction is acknowledged as a hallmark of aging and a major pathogenic factor of multiple age-associated conditions, the analysis of MDVs and, more generally, of extracellular vesicles (EVs) is recognized as a valuable research tool. The dissection of EV trafficking may help unravel new pathophysiological pathways of aging and diseases as well as novel biomarkers to be used in research and clinical settings. Here, we discuss (1) MQC pathways with a focus on mitophagy and MDV generation; (2) changes of MQC pathways during aging and their contribution to inflamm-aging and progeroid conditions; and (3) the relevance of MQC failure to several disorders, including neurodegenerative conditions (i.e., Parkinson’s disease, Alzheimer’s disease) and cardiovascular disease.

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.

The aim of the present study was to determine the intensity, duration, frequency and prevalence of postdialysis fatigue (PDF) in patients on chronic hemodialysis (PCD) with and without functional disability. Patients underwent assessment of functional ability by the Katz ADL (activity daily living) questionnaire and the Lawton and Brody scale for the instrumental activity daily living (IADL) fatigue using the SF-36 Vitality Subscale, comorbidity through the Charlson comorbidity score index (CDI), and time of recovery after hemodialysis (TIRD). We studied 271 PCD. ADL and IADL disabilities were present in 75 (27.6%) and 168 (62%) patients, respectively. Patients with ADL disability were significantly older and showed higher CDI scores, and lower levels of serum albumin and Kt/V. Prevalence of PDF was significantly higher in patients with ADL disability as well as its severity, intensity, duration and frequency. Patients with IADL disability were significantly older, had a higher CCI score, had lower levels of serum albumin and Kt/V, and had a higher severity, intensity, duration and frequency of PDF. At multivariate regression analysis, ADL disability was positively associated with age, prevalence and severity of PDF, and dialysate temperature and inversely associated with serum albumin levels. IADL disability was instead positively associated with age and dialysate temperature and inversely associated with serum albumin levels. In conclusion, prevalence and severity of PDF are significantly higher in PCD with ADL disability than in those without it. This knowledge may have important implications for the development of interventions to reduce PDF in PCD.

Aim The study aims to determine prevalence and severity of PDF and to define its associated variables. Methods In five haemodialysis units of northern-centre Italy, patients were regarded to suffer from PDF if they spontaneously offered this complaint when asked the open-ended question: Do you feel better or worse after dialysis? If worse, please specify in which way. A complaint of fatigue would be probed further with questions directed at its duration, frequency and intensity, allowing creation of a fatigue index of severity (one third of the sum of these three parameters, each rated from 1 to 5). Patients were stratified into three groups according the severity of PDF: 1) score = 0; 2) score = 1-3; 3) score > 3. Results We studied 271 patients: 164 had PDF and 107 did not. PDF patients had significantly longer time of recovery after dialysis (TIRD). TIRD was significantly associated with PDF duration, intensity, and frequency. Patients with PDF were older and had a lower ADL score. At multivariate analysis, PDF was significantly associated with TIRD. In a multivariate model that did not include TIRD, PDF was independently associated with age and ADL. Sixty patients had moderate PDF and 104 had severe PDF. In patients with severe PDF, age and dialytic age were higher, ADL and IADL scores were lower, TIRD was longer and the ultrafiltration rate was lower. At multivariate analysis, PDF severity was independently associated with TIRD. In the model without TIRD, PDF severity was associated with ADL only. Conclusion Post-dialysis fatigue is frequent and associated with age and ADL. Dialytic variables seem unrelated to PDF.

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.

The goal of the pharmacological therapy in secondary hyperparathyroidism (SHPT) is to reduce serum levels of parathyroid hormone and phosphorus, to correct those of calcium and vitamin D, to arrest or reverse the parathyroid hyperplasia. However, when nodular hyperplasia or an autonomous adenoma develops, surgery may be indicated. We reviewed the literature with the aim of defining if the echographic criteria predictive of unresponsiveness of SHPT to calcitriol therapy are valid also in the cinacalcet era and if drug therapy may reverse nodular hyperplasia of parathyroid gland (PTG). The responsiveness to therapy and regression of the nodular hyperplasia of PTG remains an open question in the calcimimetic era as well as the cutoff between medical and surgical therapy. Prospective studies are needed in order to clarify if an earlier use of cinacalcet in moderate SHPT might arrest the progression of parathyroid growth and stabilize SHPT.

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. 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. 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. 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.

Mitochondrial dysfunction is involved in the loss of muscle featuring both aging and cancer cachexia (CC). Whether mitochondrial quality control (MQC) is altered in skeletal myocytes of old patients with CC is unclear. The present investigation therefore sought to preliminarily characterize MQC pathways in muscle of old gastric cancer patients with cachexia. The study followed a case-control cross-sectional design. Intraoperative biopsies of the rectus abdominis muscle were obtained from 18 patients with gastric adenocarcinoma (nine with CC and nine non-cachectic) and nine controls, and assayed for the expression of a set of MQC mediators. The mitofusin 2 expression was reduced in cancer patients compared with controls, independent of CC. Fission protein 1 was instead up-regulated in CC patients relative to the other groups. The mitophagy regulators PTEN-induced putative kinase 1 and Parkin were both down-regulated in cancer patients compared with controls. The ratio between the protein content of the lipidated and non-lipidated forms of microtubule-associated protein 1 light chain 3B was lower in CC patients relative to controls and non-cachectic cancer patients. Finally, the expression of autophagy-associated protein 7, lysosome-associated membrane protein 2, peroxisome proliferator-activated receptor-γ coactivator-1α, and mitochondrial transcription factor A was unvarying among groups. Collectively, our findings indicate that, in old patients with gastric cancer, cachexia is associated with derangements of the muscular MQC axis at several checkpoints: mitochondrial dynamics, mitochondrial tagging for disposal, and mitophagy signaling. Further investigations are needed to corroborate these preliminary findings and determine whether MQC pathways may become target for future interventions.

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 (EAA™), 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.

Background The construct of physical frailty and sarcopenia (PF&S) identifies an age-related pre-disability condition defined by reduced physical performance and low muscle mass. Whether PF&S is characterized by perturbations of the cytokine network is presently unclear. Furthermore, the existence of gender-specific inflammatory profiles of PF&S is unknown. This study was designed to explore the association between a large panel of inflammatory biomolecules and PF&S in older adults through a multivariate statistical approach. Gender-specific inflammatory patterns were also explored. Methods One-hundred community-dwellers aged 70 years and older with PF&S and 100 non-sarcopenic, non-frail controls (nonPF&S) were enrolled. A panel of 30 circulating inflammatory biomarkers was assayed. Partial least squares discriminant analysis (PLS-DA) was employed to explore the relationship between inflammatory molecules and PF&S. Separate PLS-DA models were built for the whole sample and the two genders. Double cross-validation procedures were used to validate the predictive ability of PLS-DA models. Results The optimal complexity of the PLS-DA model built on the whole sample was found to be four latent variables. The proportion of correct classification was 75.6 ± 1.3% (82.3 ± 1.6% for enrollees with PF&S and 68.7 ± 2.5% for nonPF&S controls). The inflammatory profile of people with PF&S was defined by higher levels of P-selectin, C-reactive protein (CRP), and interferon γ-induced protein 10. NonPF&S participants were characterized by higher levels of myeloperoxidase (MPO), interleukin (IL) 8, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1-α, platelet-derived growth factor (PDGF) BB. Gender-specific PLS-DA allowed identifying a “core” inflammatory signature of PF&S, composed by higher levels of CRP, and lower concentrations of MPO, IL8, MCP-1, and PDGF-BB, with peculiar patterns of relationships for men and women. Conclusions A core inflammatory profile was identified in people with PF&S with a gender-specific signature. The dissection of the PF&S “cytokinome” will provide novel insights into the role played by inflammation in the disabling cascade and allow designing personalized treatment strategies.

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.

ContextFatigue 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.ObjectivesThe 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.MethodsA 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.ResultsFatigue 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.ConclusionDiurnal fatigue patterns during hemodialysis treatment are associated with depressive symptoms, and classical conditioning may play a role in the experience of pretreatment fatigue.