Decision-making in the implementation or withdrawal of dialysis in the old complex patient

In the last years the population of patients with end-stage renal disease has been growing and the number of patients over 74 years old on renal replacement therapy is rising. However, an increasing number of studies have shown that dialysis is not always associated with a longer life expectancy and a better quality of life for elderly patients with severe chronic comorbidity. Moreover, in selected patients conservative therapy provides a survival and quality of life comparable or even superior to that offered by dialysis. These situations pose new ethical and clinical issues. Nephrologists are increasingly faced with difficult decisions about the optimal therapeutic strategies and what is in the best interest of each patient. The new edition of the Renal Physician Association's guideline on Shared Decision-Making in the Appropriate Initiation of and Withdrawal from Dialysis takes into account these changes. For this reason the guideline advocates the use of specific parameters and tools for the prognosis assessment in order to identify the classes of patients with very poor prognosis. The importance of discussing the diagnosis, prognosis and treatment options with the patient is emphasized. Shared decision-making is the model for the physician-patient relationship. Treatment options include renal replacement therapy, not starting or stopping dialysis, and continuing medical management or palliative care. Palliative care should be offered to all patients with end-stage renal disease, whether they start or refuse dialysis and whether they continue or withdraw from dialysis. Furthermore, palliative care should be provided throughout the course of the disease, not only at the end of life

Physicians' knowledge of health-related quality of life and perception of its importance in daily clinical practice

Background: Health-related quality of life (QoL) has become a crucial outcome in medical care. However, few studies have assessed physician knowledge of QoL and rate of physicians adopting QoL measures in clinical practice. The present study aimed at assessing the level of knowledge of QoL and the perceived importance of incorporating QoL assessment in clinical practice among physicians of a tertiary level academic hospital in Rome, Italy. Materials and methods: A survey study performed through the distribution of a questionnaire assessing knowledge of QoL studies that used the SF-36 scale, participation in studies evaluating QoL as well as knowledge of journals publishing articles on QoL Physicians and residents at the hospital Policlinico Gemelli, Catholic University of Rome. Results: Three-hundred nine physicians completed the questionnaire. Thirty-eight percent % reported knowing studies on QoL and using their results in clinical practice or for research purposes; 29% reported knowing the SF-36 questionnaire; 30% stated that at least one study assessing QoL had been conducted in their department. Fourty-six percent % stated that QoL must influence much or very much diagnostic choices and an even higher percentage reported that QoL must influence much or very much therapeutic and palliative strategies (70.8% and 91.3%, respectively). Reported barriers to the use of QoL measures in clinical practice were related to time constraints (8.7%) but also to doubts on methodological issues of QoL (30.7%). The large majority of physicians (94.3%) would have used more expensive drugs if these could improve QoL. Conclusions: The present study shows that in a tertiary level academic italian hospital one third of the physicians, reported to know QoL measures and that more than 80% of them would like to use QoL in their daily clinical practice. Future studies are needed to identify the best strategies to implement the use of QoL measures in clinical practice

Functional impairment is associated with an increased risk of mortality in patients on chronic hemodialysis

Background: Functional impairment is associated with adverse outcomes in older people, as well as in patients on chronic hemodialysis. The aim of the present study was to determine the characteristics associated with functional impairment in chronic hemodialysis, and to evaluate if functional impairment represents a risk factor for reduced survival in chronic hemodialysis. Methods: All 132 chronic hemodialysis referring to the Hemodialysis Service of the Catholic University, Rome, Italy between November 2007 and May 2015 were included. All patients underwent comprehensive geriatric assessment; functional ability was estimated using two questionnaires exploring independency in bathing, dressing, toileting, transferring, continence, feeding (ADLs), and independency in using the telephone, shopping, food preparation, housekeeping, laundering, traveling, taking medications, and handling finances (IADLs). Functional impairment was diagnosed in presence of dependence in one or more ADLs/IADLs. Mood was assessed using the 30-item Geriatric Depression Scale. Logistic regression was used to evaluate factors associated with functional impairment. The association between functional impairment and survival was assessed by Cox regression. Results: ADLs impairment was present in 34 (26 %) participants, while IADLs impairment was detected in 64 (48 %) subjects. After a follow up of 90 months, 55 (42 %) patients died. In logistic regression, depressive symptoms were associated with ADLs and IADLs impairment (OR 1.12; 95 % CI = 1.02-1.23; OR 1.16; 95 % CI = 1.02-1.33; respectively). In Cox regression, ADLs impairment was associated with mortality (HR 2.47; 95 % CI-1.07-5.67) while IADLs impairment was not associated with reduced survival (HR .80; 95 % CI-.36-1.76). Conclusions: Functional impairment is associated with depressive symptoms; also, impairment in the ADLs represents a risk factor of reduced survival in chronic hemodialysis. These associations and their potential implication should be assessed in dedicated studies

Generation and Release of Mitochondrial-Derived Vesicles in Health, Aging and Disease

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

A Distinct Pattern of Circulating Amino Acids Characterizes Older Persons with Physical Frailty and Sarcopenia: Results from the BIOSPHERE Study

Physical frailty and sarcopenia (PF&S) are hallmarks of aging that share a common pathogenic background. Perturbations in protein/amino acid metabolism may play a role in the development of PF&S. In this initial report, 68 community-dwellers aged 70 years and older, 38 with PF&S and 30 non-sarcopenic, non-frail controls (nonPF&S), were enrolled as part as the "BIOmarkers associated with Sarcopenia and Physical frailty in EldeRly pErsons" (BIOSPHERE) study. A panel of 37 serum amino acids and derivatives was assayed by UPLC-MS. Partial Least Squares\u207bDiscriminant Analysis (PLS-DA) was used to characterize the amino acid profile of PF&S. The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classification was 76.6 \ub1 3.9% (75.1 \ub1 4.6% for enrollees with PF&S; 78.5 \ub1 6.0% for nonPF&S). Older adults with PF&S were characterized by higher levels of asparagine, aspartic acid, citrulline, ethanolamine, glutamic acid, sarcosine, and taurine. The profile of nonPF&S participants was defined by higher concentrations of \u3b1-aminobutyric acid and methionine. Distinct profiles of circulating amino acids and derivatives characterize older people with PF&S. The dissection of these patterns may provide novel insights into the role played by protein/amino acid perturbations in the disabling cascade and possible new targets for interventions

Nutritional Interventions in Head and Neck Cancer Patients Undergoing Chemoradiotherapy: A Narrative Review

The present review aimed to define the role of nutritional interventions in the prevention and treatment of malnutrition in HNC patients undergoing CRT as well as their impact on CRT-related toxicity and survival. Head and neck cancer patients are frequently malnourished at the time of diagnosis and prior to the beginning of treatment. In addition, chemo-radiotherapy (CRT) causes or exacerbates symptoms, such as alteration or loss of taste, mucositis, xerostomia, fatigue, nausea and vomiting, with consequent worsening of malnutrition. Nutritional counseling (NC) and oral nutritional supplements (ONS) should be used to increase dietary intake and to prevent therapy-associated weight loss and interruption of radiation therapy. If obstructing cancer and/or mucositis interfere with swallowing, enteral nutrition should be delivered by tube. However, it seems that there is not sufficient evidence to determine the optimal method of enteral feeding. Prophylactic feeding through nasogastric tube or percutaneous gastrostomy to prevent weight loss, reduce dehydration and hospitalizations, and avoid treatment breaks has become relatively common. Compared to reactive feeding (patients are supported with oral nutritional supplements and when it is impossible to maintain nutritional requirements enteral feeding via a NGT or PEG is started), prophylactic feeding does not offer advantages in terms of nutritional outcomes, interruptions of radiotherapy and survival. Overall, it seems that further adequate prospective, randomized studies are needed to define the better nutritional intervention in head and neck cancer patients undergoing chemoradiotherapy

Decision-making in the implementation or withdrawal of dialysis in the old complex patient

In the last years the population of patients with end-stage renal disease has been growing and the number of patients over 74 years old on renal replacement therapy is rising. However, an increasing number of studies have shown that dialysis is not always associated with a longer life expectancy and a better quality of life for elderly patients with severe chronic comorbidity. Moreover, in selected patients conservative therapy provides a survival and quality of life comparable or even superior to that offered by dialysis. These situations pose new ethical and clinical issues. Nephrologists are increasingly faced with difficult decisions about the optimal therapeutic strategies and what is in the best interest of each patient. The new edition of the Renal Physician Association’s guideline on Shared Decision-Making in the Appropriate Initiation of and Withdrawal from Dialysis takes into account these changes. For this reason the guideline advocates the use of specific parameters and tools for the prognosis assessment in order to identify the classes of patients with very poor prognosis. The importance of discussing the diagnosis, prognosis and treatment options with the patient is emphasized. Shared decision-making is the model for the physician-patient relationship. Treatment options include renal replacement therapy, not starting or stopping dialysis, and continuing medical management or palliative care. Palliative care should be offered to all patients with end-stage renal disease, whether they start or refuse dialysis and whether they continue or withdraw from dialysis. Furthermore, palliative care should be provided throughout the course of the disease, not only at the end of life