Cardiovascular Toxicity of Immune Checkpoint Inhibitors: Clinical Risk Factors.

PURPOSE OF REVIEW: Immune checkpoint inhibitors, such as monoclonal antibodies targeting CTLA-4, PD-1, and PD-L1, have improved the outcome of many malignancies, but serious immune-related cardiovascular adverse events have been observed. Patients' risk factors for these toxicities are currently being investigated. RECENT FINDINGS: Interfering with the CTLA-4 and PD-1 axes can bring to several immune-related adverse events, including cardiotoxic events such as autoimmune myocarditis, pericarditis, and vasculitis, suggesting that these molecules play an important role in preventing autoimmunity. Risk factors (such as pre-existing cardiovascular conditions, previous and concomitant cardiotoxic treatments, underlying autoimmune diseases, tumor-related factors, simultaneous immune-related toxic effects, and genetic factors) should be always recognized for the correct management of these toxicities.

Acute care hospital at different levels of intensity: the role of Geriatrician.

The traditional model of care is based on "disease-centered" management that requires the organization of the hospital in specialized wards, to which the patient is assigned for the main disease. The growing need to optimize economical and human resources and to promote a global approach to the patient has led to the setting up of the intensity of care model. It is a health system based on a "patient-centered" approach, where the hospital is organized in departments dedicated to patients with homogenous needs of care. In Italy, intensity of care model is currently being tested in the hospital organization, where three levels of intensity are proposed: low, medium and high. The purpose of the following review is to describe the role and importance of the Geriatrician in each of these care settings and to highlight the contradiction of a National Health System which promotes the geriatric approach to all types of patients, but does not invest in the formation and integration of the figure of the Geriatrician in clinical practice, condemning it to marginalization or even extinction.

Heart Failure and Cancer: Mechanisms of Old and New Cardiotoxic Drugs in Cancer Patients.

Although there have been many improvements in prognosis for patients with cancer, anticancer therapies are burdened by the risk of cardiovascular toxicity. Heart failure is one of the most dramatic clinical expressions of cardiotoxicity, and it may occur acutely or appear years after treatment. This article reviews the main mechanisms and clinical presentations of left ventricular dysfunction induced by some old and new cardiotoxic drugs in cancer patients, referring to the most recent advances in the field. The authors describe the mechanisms of cardiotoxicity induced by anthracyclines, which can lead to cardiovascular problems in up to 48% of patients who take them. The authors also describe mechanisms of cardiotoxicity induced by biological drugs that produce left ventricular dysfunction through secondary mechanisms. They outline the recent advances in immunotherapies, which have revolutionised anticancer therapies.

Risk of Malnutrition Evaluated by Mini Nutritional Assessment and Sarcopenia in Noninstitutionalized Elderly People.

BACKGROUND: Malnutrition indices and muscle mass and strength in the elderly are poorly investigated. Moreover, malnutrition seems to be 1 of the more important factors in the cause of sarcopenia. The presence of sarcopenia and its relationship with malnutrition indices were studied in noninstitutionalized elderly people who underwent Comprehensive Geriatric Assessment (CGA). METHODS: A total of 473 elderly subjects (mean age, 80.9 ± 6.6 years) admitted to CGA were studied. Malnutrition risk was evaluated with Mini Nutritional Assessment (MNA) score, whereas muscle mass and muscle strength were evaluated by bioimpedentiometry and hand grip, respectively. Sarcopenia was assessed as indicated in the European Working Group on Sarcopenia in Older People (EWGSOP) consensus. RESULTS: Overall prevalence of sarcopenia was 13.1%, and it increased from 6.1% to 31.4% as MNA decreased (P < .001). MNA score was lower in elderly subjects with sarcopenia (15.4 ± 4.2) than without sarcopenia (22.0 ± 4.0) (P = .024). Linear regression analysis showed that MNA score is linearly related both with muscle mass (r = 0.72; P < .001) and strength (r = 0.42; P < .001). Multivariate analysis, adjusted for several confounding variables including comorbidity and disability, confirmed these results. CONCLUSIONS: MNA score is low in noninstitutionalized elderly subjects with sarcopenia, and it is linearly related to muscle mass and muscle strength. These data indicate that MNA score, when evaluated with muscle mass and strength, may recognize elderly subjects with sarcopenia.

Impact of SPRINT results on hypertension guidelines: implications for "frail" elderly patients.

In the last years, guidelines for the treatment of hypertension recommended individualized blood pressure goals for geriatric population because of elderly susceptibility to adverse outcomes and higher mortality rate deriving from the excessive blood pressure lowering, especially in "frail" elderly. Recent findings from the SPRINT study, which demonstrated that intensive blood pressure lowering was associated with lower rates of cardiovascular events and mortality in both hypertensive fit and frail elderly subjects compared to standard treatment, heavily influenced the recent US guidelines. In SPRINT sub-study analysis of adults aged ≥75 years, the most controversial issue appears the method of blood pressure measurement, the selection of patients and related-frailty degree that appears to be very light. Accordingly, it has been described that light frailty is related to good outcomes in older adults. SPRINT findings in "frail elderly patients" cannot be applied to the clinical practice because this condition has been clearly under-estimated. Thus, frailty status should be routinely and correctly quantified in order to identify the frailty degree and to find the best harms-benefits balance of antihypertensive drug treatment in frail older adults.

Orthostatic Hypotension in the Elderly: A Marker of Clinical Frailty?

BACKGROUND: Orthostatic hypotension (OH) has high prevalence in frail older adults. However, its effect on mortality, disability, and hospitalization in frail older adults is poorly investigated. Thus, we assessed the relationship between the prevalence of OH and its effect on mortality, disability, and hospitalization in noninstitutionalized older adults stratified by frailty degree. METHODS: Prospective, observational study of 510 older participants (≥65 years of age) consecutively admitted to a geriatric evaluation unit to perform a geriatric comprehensive assessment. MEASUREMENTS: Clinical frailty was assessed using the Italian frailty index (40 items). Systolic blood pressure (mm Hg), diastolic blood pressure (mm Hg), and heart rate (bpm) were evaluated in clinostatic position and after 1, 3, and 5 minutes of orthostatic position. OH was defined with a decrease of 20 mm Hg in systolic blood pressure and/or a decrease of 10 mm Hg in diastolic blood pressure. RESULTS: OH prevalence was 22%, and it increased from 9.0% to 66.0% according to frailty degree (P for trend <.001). When stratified by frailty degree, mortality, disability, and hospitalization increased from 1.0% to 24.5%, from 39.0% to 77.0% and from 14.0% to 32.0% in the absence, and from 0.0% to 35.5%, from 42.0% to 95.5% and from 19.0% to 65.5% in the presence of OH, respectively (P < .01 vs absence of OH). Multivariate analysis showed that the Italian frailty index is more predictive of mortality, disability, and hospitalization in the presence than in the absence of OH. CONCLUSIONS: OH is a common condition in frail older adults, and it is strongly associated with mortality, disability, and hospitalization in the highest frailty degree. Thus, OH may represent a new marker of clinical frailty.

Sarcopenia: assessment of disease burden and strategies to improve outcomes.

Life expectancy is increasing worldwide, with a resultant increase in the elderly population. Aging is characterized by the progressive loss of skeletal muscle mass and strength - a phenomenon called sarcopenia. Sarcopenia has a complex multifactorial pathogenesis, which involves not only age-related changes in neuromuscular function, muscle protein turnover, and hormone levels and sensitivity, but also a chronic pro-inflammatory state, oxidative stress, and behavioral factors - in particular, nutritional status and degree of physical activity. According to the operational definition by the European Working Group on Sarcopenia in Older People (EWGSOP), the diagnosis of sarcopenia requires the presence of both low muscle mass and low muscle function, which can be defined by low muscle strength or low physical performance. Moreover, biomarkers of sarcopenia have been identified for its early detection and for a detailed identification of the main pathophysiological mechanisms involved in its development. Because sarcopenia is associated with important adverse health outcomes, such as frailty, hospitalization, and mortality, several therapeutic strategies have been identified that involve exercise training, nutritional supplementation, hormonal therapies, and novel strategies and are still under investigation. At the present time, only physical exercise has showed a positive effect in managing and preventing sarcopenia and its adverse health outcomes. Thus, further well-designed and well-conducted studies on sarcopenia are needed.

Oxidative stress, aging, and diseases.

Reactive oxygen and nitrogen species (RONS) are produced by several endogenous and exogenous processes, and their negative effects are neutralized by antioxidant defenses. Oxidative stress occurs from the imbalance between RONS production and these antioxidant defenses. Aging is a process characterized by the progressive loss of tissue and organ function. The oxidative stress theory of aging is based on the hypothesis that age-associated functional losses are due to the accumulation of RONS-induced damages. At the same time, oxidative stress is involved in several age-related conditions (ie, cardiovascular diseases [CVDs], chronic obstructive pulmonary disease, chronic kidney disease, neurodegenerative diseases, and cancer), including sarcopenia and frailty. Different types of oxidative stress biomarkers have been identified and may provide important information about the efficacy of the treatment, guiding the selection of the most effective drugs/dose regimens for patients and, if particularly relevant from a pathophysiological point of view, acting on a specific therapeutic target. Given the important role of oxidative stress in the pathogenesis of many clinical conditions and aging, antioxidant therapy could positively affect the natural history of several diseases, but further investigation is needed to evaluate the real efficacy of these therapeutic interventions. The purpose of this paper is to provide a review of literature on this complex topic of ever increasing interest.