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Background. There are scant data about the effectiveness of high flow nasal cannula (HFNC) oxygen therapy in patients hospitalized with severe acute respiratory failure (ARF) in non-intensive medical wards, particularly regarding the effect on arterial oxygenation compared to conventional oxygen therapy (COT) and non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP). Methods. In a retrospective observational study, oxygenation parameters were measured before and immediately after HFNC initiation in 37 consecutive patients hospitalized in a geriatric ward in 2017. Results. HFNC was used as escalation therapy for untreatable hypoxia after failure of NIV/CPAP (n=18) or COT (n=19). Twenty-two patients died, 2 were transferred to the intensive care unit, while 13 were discharged alive. A “do not intubate” status was identified in 17 of the 22 deceased patients. Partial pressure of oxygen (pO2, p< 0.0001), oxygen saturation (SO2, p< 0.0001), pO2/fraction of inspired oxygen ratio (p=0.004) and peripheral SO2 measured by pulse oximetry (p< 0.0001) significantly increased soon after HFNC application. Oxygenation improvements were greater after escalation from NIV/CPAP and in patients discharged alive. Conclusion. HFNC significantly improved oxygenation in severe ARF after failure of COT or NIV/CPAP and may be particularly suitable for older patients hospitalized in non-intensive medical wards.

Older adults are frequently stigmatized for improper emergency department (ED) visits and hospitalizations. In this study, we aimed to investigate the relationship between age and appropriateness of ED visits, and the mismatching between ED clinical severity and hospitalizations.We carried out a nationwide assessment of Italian Informative System for the Emergency and Urgency data from 1 January 2015 to 31 December 2015 including patients admitted to all the Italian EDs for any reason. Appropriateness of ED visits was defined as a yellow/red/black color code (potentially life-threatening/dead patients), whereas clinical severity/hospitalization mismatching was defined as hospital admission after validated ED green/white codes. Analyses dedicated to people aged ≥75 years were carried out.There were 20 400 071 ED visits (3 444 091 aged ≥75 years), which increased with age, up to650/1000 inhabitants aged ≥90 years. The appropriateness of ED visits increased with age, from 6.3% in the 5-9 years age group to 44.2% in the 95-99 years age group. Clinical severity/hospitalization mismatching decreased with age, from 62.9% in the 30-34 years age group to 27.7% in the 95-99 years age group. At ED presentation, 21.6% of patients aged ≥75 years complained of non-specific symptoms, and hospital discharge diagnoses frequently differed from the ED admission diagnoses; 11.4% died during hospitalization and 8.8% were discharged to long-term care facilities.The request for ED care and the admission to acute care ward are commonly appropriate for older patients. Clinical presentation at ED admission is frequently atypical. Health care systems should aim at improving outpatients' management to reduce the ED care need, but also at optimizing in-hospital strategies and pathways for older adults. Geriatr Gerontol Int 2022; 22: 917-923.

The need for major information in meta-research (i.e. the part of medicine interested in systematic reviews [SRs] and meta-analyses [MAs]) is increasing. In the last years we are observing an exponential rate of publications as SRs/MAs in geriatric medicine. In order to better assess the interest in meta-research, we proposed a survey to know the knowledge and the needs in meta-research in geriatrics. A short survey (about 5 minutes) was freely available in the Italian Society of Hospital and Community Geriatrics (SIGOT) website and diffused in social networks. The survey was available during the entire 2019. The survey regards demographic information, previous research activities and the knowledge of the participant on meta-research. Altogether, 148 participants mainly men (=65.5%) and mainly aged 36 to 44 years and working in hospital from all Italian regions completed the survey. Responders read more than 20 articles in the previous year (=58.1%), including 10-20 SRs/MAs (25%). Many respondents (41.9%) had published >20 articles during their life. At the same time, a consistent part of the respondents recognized the importance of metaresearch for clinical practice and almost all the participants recognized that metaresearch has changed their daily clinical approach to the patient. Almost all the participants would like to have more training in meta-research suggesting that SIGOT should organize training courses for metaresearch in geriatric medicine. In conclusion, our survey showed that the interest in SRs/MAs is high, whilst the knowledge is still limited suggesting that education is needed to fill the gap in this field.

The emergent coronavirus-19 disease (COVID-19) pandemic posed and still poses serious issues in the management of the inpatients and in the resource allocation, in particular for those patients requiring Intensive Care Unit (ICU) management. Epidemiological data clearly suggest that multimorbid older patients have the poorest prognosis. However, it is conceivable that age and number of comorbidities alone do not reflect the real condition and the expected prognosis of the patients affected by COVID-19. A different approach based on comprehensive geriatric assessment (CGA) could help to better identify older patients more at risk of dismal outcomes and who, at some point of their clinical course, will need the ICU admission. The Multidimensional Prognostic Index (MPI) is a well-accepted tool derived from a standard CGA which allows to measure prognosis of older patients in different clinical settings including hospital. Therefore, we designed a multicenter, prospective, observational study to evaluate the role of MPI in predicting risk of ICU admission and in-hospital mortality among 500 COVID-19-positive older subjects admitted to geriatric and internal medicine wards. In addition, risk of re-hospitalization, institutionalization and death after 3 months from discharge will be assessed. The MPI yields a straightforward value from 0 to 1 and might be able to adequately stratify complex, vulnerable COVID-19 patients for best possible decision-making and treatment allocation.

Das gleichzeitige Vorliegen von chronisch-obstruktiver Lungenerkrankung (COPD) und obstruktivem Schlafapnoe-Syndrom bei demselben Patienten wird als «Overlap-Syndrom» bezeichnet und stellt einen ungünstigen Prognosefaktor für den Patienten dar. Starke Bronchodilatation kann in der Behandlung dieser Erkrankung sinnvoll sein. Gemäß der GOLD-Leitlinie 2017 kann die Kombination aus Indacaterol und Glycopyrronium positive synergistische Effekte auf die glatten Muskelzellen und den Widerstand der Atemwege haben, mit besonders ausgeprägter Wirksamkeit im Hinblick auf die Hyperinflation der Lunge. So bewirken inhalative Bronchodilatatoren positive Veränderungen der dynamisch determinierten Komponenten der Hyperinflation der Lunge in Ruhe und tragen dazu bei, die hyperinflatierte Lunge zu entleeren. Besonders wichtig ist dies für die Verbesserung der Dyspnoe, körperlichen Belastbarkeit und nächtlichen Sättigung, vor allem in Kombination mit CPAP-Überdruckbeatmung, wie in unserer Fallserie beschrieben. Wir berichten hier über 3 Fälle von COPD; die Patienten wurden in stabilem klinischem Zustand aufgrund von potenziell auf eine obstruktive Schlafapnoe hindeutenden Symptomen der Abteilung für Pathophysiologie der Atemwege am «Mariano Santo»-Krankenhaus in Cosenza zugewiesen und dort erfolgreich mit Indacaterol und Glycopyrronium in fester Dosierung behandelt. Übersetzung aus Respiration 2018;95(suppl 1):15-18 (DOI: 10.1159/000487179)

Acute respiratory deteriorations are frequent and dangerous events in patients with lung comorbidities. The identification of the underlying cause(s) is challenging, also owing to chronic and unrecognized imaging and functional lung abnormalities. Oxygen therapy is the first support, but is burdened with possible complications and risk of failure. Non-invasive ventilation and high-flow nasal cannula oxygen therapy are important therapeutic resources.

In recent years, many research groups are trying to quantify the physiological signals of an individual, proposing new models to assess the complex dynamics of biological control systems. Indeed, life coincides with the good handling of the structures in the organism and of physiological control mechanisms, while disease and death coincide with the loss of structure and of coordinated functions. The homeodynamic systems which normally govern health are the same that cause pathological events when activated inadequately, or rather, when the balance between order and chaos of the elementary physiological processes is no longer effectively controlled in relation to any type of stress, both external and internal to the body. In a complex system, loss or alteration of communication between physiological signals means pathology. In this paper a signal analysis method based on Entropy (E), Lyapunov exponent (1), Median Absolute Deviation (MAD), Multiscale Entropy (MSE), is proposed to estimate the complexity of long-range temporal correlation heart rate (HR) time series for an elderly person and a young person both healthy. These new methods could improve overall understanding of the physiological system of the human organism, by adopting new models and experimental paradigms, such as those of fractality and entropy, who have the ability to direct from an organ medicine to a modern systemic medicine.

Introduction: Four patients with symptoms suggestive of OSA came to our attention. Diagnosis of GOLD 2B COPD dated two years, suggested starting LAMA therapy with glycopirronium. Aim of the study:in this case series was to highlight the complexity of treating patients with overlap syndrome Methods: Spirometry, six-minute-walking test (WT), modified Medical Research Council (mMRC)dyspnea scale and a full-night cardiorespiratory study were assessed. All patients were diagnosed OSAS and referred to continuous positive airway pressure (CPAP)therapy and daily oxygen therapy. After four months, all patients were re-evaluated. Results: an improvement of lung function at night was showed, although nocturnal desaturation analysis were still prolonged. Dyspnea on exertion still persisted.A increased Motley index, expressing dynamic hyperinflation persisted.GOLD 2017 suggest treating COPD patients with persisting symptoms with LABA plusLAMA combination. We switched our patients to the indacaterol/glycopirronium combination therapy. After Three months, patients were re-evaluated for lung function and overnight respiratory function was checked by nocturnal pulse oximetry testing during CPAP ventilation without oxygen addition. The results showed a significant improvement in the Motley index (reducing air trapping), WT and mMRC. Therapy was confirmed with suspension of oxygen administration during the ventilator support. Conclusions: In our report we maximized bronchodilation with the association indacaterol/glycopirronium, resolving persistent hyperinflation and being able to stop oxygen administration. Effective bronchodilation is a key strategy for improving exercise performance and night saturation.

The coexistence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea syndrome in a single patient is known as “overlap syndrome,” and worsens the prognosis of the affected subjects. A marked bronchodilation may be useful for the treatment of this condition. In fact, as stated in the GOLD 2017 guidelines, the combination of indacaterol/glycopyrronium may exert positive synergistic effects on smooth muscle cell and airway resistance, with a more pronounced efficiency in reducing lung hyperinflation. Noteworthy, inhaled bronchodilators favorably alter the dynamically determined components of resting lung hyperinflation and help deflate the overinflated lungs. This is particularly important in order to improve dyspnea, exercise performance, and night saturation, especially when combined with continuous positive airway pressure ventilation, as reported in our case series. We report 3 cases of patients with COPD in a stable clinical condition, referred to the Department of Respiratory Pathophysiology at the “Mariano Santo” Hospital in Cosenza, due to possible symptoms suggestive of obstructive sleep apnea, and who were successfully treated with indacaterol/glycopyrronium at a fixed dose.

Polypharmacy and potentially inappropriate medications (PIMs) are known to affect several negative outcomes in older patients. However, studies comparatively assessing polypharmacy and PIMs in relation to readmission are distinctively lacking. To compare the impact of polypharmacy and PIMs on 3-month readmission among older patients discharged from acute care hospital. Our series consisted of 647 patients consecutively enrolled in a multicenter observational study. The outcome of the study was the occurrence of any admission during the 3-month follow-up after discharge. Polypharmacy was defined as use of more than eight medications. PIMs were identified using 2015 version of Beers and Screening Tool of Older Persons Prescriptions (STOPP) criteria. Statistical analysis was performed using logistic regression models. After adjusting for potential confounders, polypharmacy (OR 2.72, 95% CI 1.48–4.99) was found associated with the outcome, while Beers (OR 0.85, 95% CI 0.46–1.56), STOPP (OR 1.60, 95% CI 0.85–3.01), or combined Beers and STOPP violations (OR 0.99, 95% CI 0.57–1.74) were not. The association between polypharmacy and 3-month readmission was confirmed in logistic regression models including Beers (OR 2.88, 95% CI 1.55–5.34), STOPP (OR 2.64, 95% CI 1.43–4.87), or combined Beers and STOPP violations (OR 2.80, 95% CI 1.51–5.21). Besides confirming that polypharmacy should be considered as a marker for readmission risk among older patients discharged from acute care hospital, our findings suggest that the association between polypharmacy and 3-month readmission is substantially independent of use of PIMs. Polypharmacy, but not PIMs was significantly associated with readmission. Hospitalization should always be considered as a clue to individuate unnecessary polypharmacy and to reduce the burden of medications whenever possible.

Aims Acute diseases and related hospitalization are crucial events in the disabling process of elderly individuals. Most of the functional decline occurs in the few days before hospitalization, as a result of acute diseases in vulnerable patients. The aim of the present study was to identify determinants of prehospital components of functional decline. Methods This was a prospective observational study carried out in three acute geriatric units and two general medicine units of three Italian hospitals. The participants were 1281 patients aged 65 years or older admitted to hospital for acute illnesses and discharged alive. Functional status 2 weeks before hospitalization (preadmission) and at hospital admission was measured by the Barthel Index to identify patients with prehospital decline. In this group of decliners, the percentage extent of prehospital decline (PEPD) was also calculated. Results Prehospital decline occurred in 541 (42.2%) patients, who were hospitalized mostly in geriatric wards (55.6%). Older age (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.04–1.08) and dementia (OR 2.8, 95% CI 1.4–5.4) were significant predictors of prehospital decline, whereas a high preadmission function was protective (OR 0.992, 95% CI 0.987–0.997). Pulmonary disease as primary discharge diagnosis was also associated with prehospital decline (OR 1.8, 95% CI 1.3–2.5) after adjustment for age, diagnosis of dementia and preadmission function. Amongst decliners, a low preadmission function and the origin of patients (from emergency rooms or other hospital units) were associated with larger PEPD. Conclusions Using a clinically meaningful change to define decline, disease-related prehospital disability is observed mainly in persons with low preadmission function, older age and dementia. Geriatr Gerontol Int 2014; 14: 769–777.

Aim Restrictive lung dysfunction (RLD; defined as reduced forced vital capacity [FVC] in the presence of normal forced expiratory volume in 1 s [FEV1]/FVC ratio) is highly prevalent in the elderly, and is associated with diabetes, metabolic syndrome (MetS) and abdominal obesity. The aim of this study was to assess the relative contribution of diabetes, MetS and abdominal obesity in characterizing RLD in the elderly. Methods This was cross-sectional analysis of 192 consecutive, community-dwelling persons (mean age 70.8 ± 8 years). The participants were grouped according to the number of MetS components (i.e. 0, 1, 2, 3 or 4) and the presence of diabetes. According to the Adult Treatment Panel-III criteria, participants with three or four components were considered to be affected by MetS. Independent correlates of RLD and obstructive lung dysfunction (OLD; FEV1/FVC

Introduction: Glycopyrronium bromide (GB) is an antimuscarinic compound,exerts its action by inhibiting bronchoconstriction,mainly blocking M3 and M1 muscarinic receptors.The damage caused by inhalation of toxic particles such as cigarette smoke and environmental pollutants, affects the small airways. Aim of the study: We tried to verify if there is a relationship between alterations of small airways and efficacy of bronchodilation evaluated using GB;exercise tolerance was assessed by perfoming the walking test (WT). Methods: We selected 42 patients (24 female/ 18 male), with: mean age 66.8 ± 9.7;normal FEV1/FVC ratio % 77.45 ± 4.86; reduced FEF 25-75% 42.9 ± 10.50; increased RV/TLC ratio % (dynamic hyperinflation index) 132.66 ± 6.41; FEV1 1.85 ± 0.54 liters; FVC 2.39±0.71 liters; SR tot (airway resistance) 168.10 ± 42.53 KPa*S;TLC 98.26 ± 8.94 liters;WT 318.39 ± 36.60 meter;MMRC dypnea scale 1.48 ± 0.77.Patients were treated with GB and underwent a second visit after 4 months. Results: After the treatment, a significant improvement was recorded regarding FVC (P=0.04),FEV1/FVC ratio % (P=0.01), FEF 25-75 % (P Conclusions: In this real life experience, GB has proven to exert favourable effects on lung hyperinflation,with positive reflexes also in measurable functional parameters, such as dyspnea and exercise capacity.In this setting,small airways dysfunction has been successfully managed by an anticholinergic agent.

OBJECTIVES: To investigate the characteristics of patients who regain function during hospitalization and the differences in terms of functional outcomes between patients admitted to geriatric and general medicine units. DESIGN: Multicenter, prospective cohort study. SETTING: Acute care geriatric and medical wards of five Italian hospitals. PARTICIPANTS: One thousand forty-eight elderly patients hospitalized for acute medical diseases. MEASUREMENTS: Functional status 2 weeks before hospital admission (baseline), at admission, and at discharge, as measured using the Barthel Index (BI). RESULTS: Geriatric patients were older (P

We aimed at verifying whether unrecognized chronic kidney disease (CKD) (i.e., reduced estimated glomerular filtration rate in spite of normal serum creatinine) has prognostic significance in an unselected population of older patients discharged from 11 acute care hospitals located throughout Italy. Our series consisted of 396 participants aged 70 and older. Estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease (MDRD) study equation. We compared three groups: Normal renal function (normal serum creatinine levels and normal eGFR), concealed (normal serum creatinine levels and reduced eGFR), or overt (increased creatinine levels and reduced eGFR) renal failure. The relationship between renal function and 1-year mortality was evaluated using Kaplan-Meier curves and Cox regression analysis including potential confounders. Overall, 56 patients died over a cumulative follow-up time of 335 months, with an estimated incidence rate of 16.7/100 person-year (PY). The corresponding figures in patients with normal renal function, concealed CKD, and overt CKD were 9.8/100 PY (95% CI, 5.7-15.7), 28.3/100 PY (95% CI, 13.6-52.1), and 23.0 (95% CI, 15.4-33.0), respectively (log rank test p = 0.006). According to the fully adjusted model, both concealed (hazard ratio [HR], 2.35; 95% CI, 1.09-6.01) and overt CKD (HR, 2.09; 95% CI, 1.05-5.34) were significantly associated with the outcome. Concealed CKD contributes to profile the elderly patient at greater risk of death after being discharged from acute care medical wards. If confirmed in broader populations, this finding might have both clinical and epidemiological implications.

Patients classified as having a “poor lung function” in large populations studies are at increased risk of atherothrombosis, but potential mechanisms are unclear. A large proportion of these people are affected by chronic obstructive pulmonary disease (COPD), a recognized risk factor for vascular events. Systemic inflammation is the main atherothrombotic abnormality in COPD, but hypoxia-related platelet activation, pro-coagulant status and oxidative stress may play a role. Systemic inflammation is presumably a leading mechanism of atherothrombosis also in people who have a “restrictive” spirometric dysfunction, rather than the classic obstructive pattern of COPD. Many persons with “poor lung function” are affected by diabetes and their cardiovascular risk is therefore linked to the diabetic status. Patients affected by diabetes tend to have a “restrictive” dysfunction, rather than COPD. Recent studies show that restriction at spirometry precedes the onset of diabetes, thereby representing a marker of mechanisms involved in the pre-diabetic, insulin-resistant state. This is also proved by the fact that most patients with metabolic syndrome, a pre-diabetic condition, have a restrictive ventilatory pattern at spirometry. A significant proportion of people with “poor lung function” have visceral obesity, a cardiovascular risk factor. By hampering lung expansion, visceral obesity causes a restrictive ventilatory pattern. In conclusion, the term “poor lung function” includes various chronic illnesses with different mechanisms of atherothrombosis. Research is needed for better understanding why persons with lung dysfunctions have higher cardiovascular risk, and for identifying adequate preventive strategies.

SummaryObjectivesTo evaluate the association between pulmonary restriction and mortality in the elderly, taking into account potential confounders not considered in the past (disability, cognitive dysfunction, diabetes, and visceral obesity).DesignLongitudinal study.SettingCommunity-based.ParticipantsTwelve hundred sixty-five patients (51.9% men) aged 65–97 years old from the Salute Respiratoria nell'Anziano (SaRA) Italian multicentric study.MeasurementsParticipants were divided in 4 groups: normal spirometry (NS): FEV1/FVC≥70%, FVC≥80% of predicted; restrictive ventilatory pattern (RVP): FEV1/FVC≥70%, FVC

The anti-diabetic drug phenformin was banned in many countries because of the high risk of lactic acidosis (LA), mostly arising in elderly with predisposing conditions [1]. To our knowledge, phenformin is still legal in Italy, Brazil, Uruguay, China, Poland, Greece and Portugal, and cases of LA are continuously reported worldwide [2–5]. Phenformin-induced LA is an unpredictable complication that may occur even in people without predisposing diseases, causing death in 50% of cases [1]. In addition, LA is often misdiagnosed, and many cases may go unrecognized, particularly in older persons affected by various chronically symptomatic illnesses. As recently emphasized, the reported cases of phenformin-induced LA may thus represent only ‘‘the tip of an iceberg’’ [3]. Phenformin can always be replaced by metformin, a safe and useful drug. A recent meta-analysis showed that metformin does not cause LA more frequently than diabetes per se [6]. Age is an absolute contraindication to phenformin, because older patients have increased prevalence of medical conditions favouring LA [1]. These persons, however, may just represent the subgroup with the highest prescription rate, since they are less likely to attend diabetes outpatients clinics where phenformin prescription is avoided [7]. We aimed to test this hypothesis in 1,273 elderly diabetic patients from the Gruppo Italiano di Farmacovigilanza nell’ Anziano Study, consecutively hospitalized in 1997–1998 in 81 participating wards of Internal or Geriatric Medicine located throughout Italy [8]. Patients were grouped according to whether or not they were taking phenformin before hospitalization. Comparison of users versus non users of phenformin before admission was made by ANOVA one way for continuous variables and chi-square test for categorical variables. Variables significantly distinguishing groups in the univariate analysis were entered in a multivariable logistic regression model to identify independent correlates of phenformin use before hospitalization (dependent variable). Odds ratios (OR) and 95% confidence intervals (CI) were calculated. All statistical analyses were performed using SPSS software (version 10.0; SPSS Inc. Chicago, IL). Phenformin was used by 151 patients (11.9%). Mean age was significantly higher in users compared to non users (74.9 ± 10.3 vs. 72.4 ± 11.7, P = 0.015). The clinical characteristics of users and non-users, and the results of univariate analysis are described in Table 1. The multivariable logistic regression analysis demonstrated that age C80 years (OR 1.90, 95% CI 1.09–3.31) and a combined use of insulin and oral hypoglycaemic agents (OR 3.05, 1.56–5.96) were positive correlates of phenformin use, whereas dementia (OR 0.20, 0.06–0.66), decompensated F. L. Fimognari (&) R. Pastorelli Unita Operativa di Medicina Interna, ASL Roma G, Ospedale Leopoldo Parodi-Delfino, Colleferro (Rome), Via F. Verdinois 30, 00159 Rome, Italy e-mail: filippo.fimognari@virgilio.it

Altered autonomic regulation of cardiac function may contribute to the onset of cardiovascular disease and provide a substrate for malignant ventricular arrhythmias. This study was designed to assess cardiovascular neuroautonomic status in healthy subjects with short-term power spectral analysis of heart rate variability, including a group over 100 years of age, to identify a neuroautonomic pattern that could help to protect ultra-centenarians against cardiovascular disease. One hundred and twelve subjects (22 men and 90 women, age range 20 to 107 years) were subdivided into five age groups:40 years (N=26, mean age 30.6+/-0.9); 41 to 60 years (N=27, mean age 51.9+/-1.2); 61 to 80 years (N=37, mean age 70.3+/-1.1); 81 to 100 (N=10, mean age 85.2+/-0.8) and older than 101 years (N=13, mean age: 103.6+/-0.6). Power spectral analysis with autoregressive algorithm provides two indexes of autonomic activity: a low-frequency component oscillating around 0.10 Hz, mainly reflecting sympathetic activity and a high-frequency component around 0.30 Hz, reflecting parasympathetic activity. Subjects 40 years of age or younger had significantly higher spectral high-frequency power values expressed in logarithmic form than the other age groups (P0.05), the age group from 41 to 100 years had values similar to those of the other groups. However, the age group over 101 years had significantly higher values than the group from 81 to 100 years (P0.05). Low-frequency spectral density expressed in logarithmic form and in normalized units decreased with age (P0.0001). These data confirm an age-related decline in sympathetic activity. Compared with elderly subjects from 81 to 100 years of age ultra-centenarians have significantly higher spectral parasympathetic indexes. Parasympathetic predominance may be the neuroautonomic feature that helps to protect ultra-centenarians against cardiovascular disease.

Acute diseases and related hospitalization are crucial events in the disabling process of elderly individuals. Most of the functional decline occurs in the few days before hospitalization, as a result of acute diseases in vulnerable patients. The aim of the present study was to identify determinants of prehospital components of functional decline.This was a prospective observational study carried out in three acute geriatric units and two general medicine units of three Italian hospitals. The participants were 1281 patients aged 65 years or older admitted to hospital for acute illnesses and discharged alive. Functional status 2 weeks before hospitalization (preadmission) and at hospital admission was measured by the Barthel Index to identify patients with prehospital decline. In this group of decliners, the percentage extent of prehospital decline (PEPD) was also calculated.Prehospital decline occurred in 541 (42.2%) patients, who were hospitalized mostly in geriatric wards (55.6%). Older age (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.04-1.08) and dementia (OR 2.8, 95% CI 1.4-5.4) were significant predictors of prehospital decline, whereas a high preadmission function was protective (OR 0.992, 95% CI 0.987-0.997). Pulmonary disease as primary discharge diagnosis was also associated with prehospital decline (OR 1.8, 95% CI 1.3-2.5) after adjustment for age, diagnosis of dementia and preadmission function. Amongst decliners, a low preadmission function and the origin of patients (from emergency rooms or other hospital units) were associated with larger PEPD.Using a clinically meaningful change to define decline, disease-related prehospital disability is observed mainly in persons with low preadmission function, older age and dementia.

Much evidence indicates an involvement of the sympathetic nervous system in the genesis of silent myocardial ischemia. The authors assessed autonomic system activity by power spectrum analysis of heart rate variability in 21 elderly hypertensive men with and without angiographically confirmed coronary artery disease and compared the results with those from an age-matched control group. In the analysis an autoregressive algorithm was used to determine the power spectrum from an electrocardiographic recording of 512 consecutive RR intervals. The autonomic nervous system induces two distinct sinusoids: a low-frequency signal attributable to sympathetic activity and a high-frequency vagal response. In the hypertensive patients with coronary disease the authors also evaluated sympathetic activation after double-blind, placebo-controlled administration of metoprolol (100 mg/day), followed by amlodipine (10 mg/day), quinapril (20 mg/day), and amlodipine (5 mg/day) plus quinapril (10 mg/day). (continued on next page) Spectrum analysis showed significantly increased sympathetic activity in the hypertensive patients with coronary disease (low frequency: 58.4 ±2.0, P < 0.001) as compared with controls (36.21 ± 1.0, P < 0.001) and hypertensive subjects without coronary disease (low frequency: 25.2 ±0.6 , P < 0.001) but significantly reduced parasympathetic activity (39.4 ±2.0, P < 0.001) with respect to hypertensive patients without heart disease (42.5 ±2.0, P < 0.001) and controls (60.3 ±2.0). Treatment with metoprolol, quinapril, and amlodipine plus quinapril significantly reduced sympathetic tone (P < 0.05).

Restrictive lung dysfunction (RLD; defined as reduced forced vital capacity [FVC] in the presence of normal forced expiratory volume in 1 s [FEV1]/FVC ratio) is highly prevalent in the elderly, and is associated with diabetes, metabolic syndrome (MetS) and abdominal obesity. The aim of this study was to assess the relative contribution of diabetes, MetS and abdominal obesity in characterizing RLD in the elderly.This was cross-sectional analysis of 192 consecutive, community-dwelling persons (mean age 70.8 ± 8 years). The participants were grouped according to the number of MetS components (i.e. 0, 1, 2, 3 or 4) and the presence of diabetes. According to the Adult Treatment Panel-III criteria, participants with three or four components were considered to be affected by MetS. Independent correlates of RLD and obstructive lung dysfunction (OLD; FEV1/FVC0.70) were assessed by logistic regression models.The mean age of the sample population was 70.8 years. FVC expressed as percent of the predicted value declined for an increasing number of MetS components (P0.0001), but diabetes did not account for further ventilatory decline. Consistently, MetS (OR 3.03, 95% CI 1.16-7.89) and abdominal obesity (OR 4.89, 95% CI 1.17-20.3), but not diabetes, were independently associated with RLD. OLD did not worsen for an increasing number of MetS components and was only related to age (OR 1.07, 95% CI 1.01-1.13) and smoking (OR 1.04, 95% CI 1.01-1.06).MetS and abdominal obesity, two conditions of prediabetes, but not diabetes itself, are closely associated with RLD. These conditions might be implicated in the pathogenesis of the RLD, which is frequently observed in diabetic patients.

Objective: To report a case of erlotinib-induced hepatitis complicated by fatal lactic acidosis in an elderly patient with lung adenocarcinoma and diabetes mellitus. Case Summary: A 77-year-old man with stage IIIB lung adenocarcinoma was treated with erlotinib 100 mg/day, an epidermal growth factor receptor inhibitor, after failure of chemotherapy and radiotherapy. The patient also had type 2 diabetes mellitus; metformin therapy had been initiated 5 years before presentation. Twelve days after the start of erlotinib therapy, he developed drug-related acute hepatitis complicated by renal deterioration (aspartate aminotransferase 1400 U/L, alanine aminotransferase 1299 U/L, creatinine 4.4 mg/dL, urea nitrogen 55 mg/dL). Viral causes of hepatitis were excluded and a recent computed tomography scan had ruled out liver metastases. According to the Roussel-Uclaf causality assessment method, the erlotinib-related hepatitis was classified as probable. The patient's condition was soon complicated by the onset of lactic acidosis, which caused death 2 hours after admission. Discussion: In this patient, lactic acidosis was promoted by erlotinib-related hepatitis with initial liver failure (decreased lactate clearance), concomitant metformin treatment (increased lactate production), and acute renal deterioration (metformin accumulation). This is the second case of fatal erlotinib-induced liver toxicity in a patient with lung cancer. In the previous case, death occurred after about 11 days and was entirely due to fulminant hepatitis, whereas in our patient, the liver injury only initiated a drug–disease interaction that caused fatal lactic acidosis within a lew hours. Conclusions: Liver function should be carefully monitored during erlotinib treatment, particularly in elderly and frail patients on multiple medications. Further studies are therefore needed for better testing the safety of erlotinib in such people, commonly encountered in the real world, but often excluded from participation in randomized trials of cancer treatment.

Patients with chronic obstructive pulmonary disease (COPD) are at increased atherothrombotic risk. Preliminary findings have suggested that COPD patients may have increased plasma total homocysteine (tHcy), a cardiovascular risk factor often caused by a poor B vitamin status, but plasma levels of such vitamins were not measured. The aim of this study was to investigate hyperhomocysteinaemia in COPD and to determine whether it may be secondary to poor plasma concentrations of B vitamins.We performed a case-control, cross-sectional study of 42 patients with COPD and 29 control subjects. Folate, vitamin B12, vitamin B6, tHcy, renal function, C-reactive protein, blood gases and lipids were measured in patients and controls. COPD patients had higher plasma tHcy (median: 13.9mumol/l, interquantile range [IQR]: 12.1-18.5 versus 11.5, IQR: 10.1-14, p=0.002) and lower circulating folate (median: 2.5ng/ml, IQR: 1.2-3.3 versus 2.8, IQR: 2.1-4 of controls, p=0.03) than controls had. Compared to the control group, COPD was associated with higher tHcy concentrations also after adjusting for smoking, heart failure, renal function and C-reactive protein with logistic regression analysis (OR 1.36, 95% CI 1.06-1.72, p=0.01). In the COPD group, low levels of folate (beta=-0.27, p=0.02) and vitamin B12 (beta=-0.24, p=0.04), and hypertriglyceridaemia (beta=0.580, p0.0001) were independent predictors of the presence of high tHcy concentrations in a multiple linear regression model (adjusted R(2)=0.522).COPD patients have a poor B vitamin status and, as a consequence, increased tHcy. These abnormalities may contribute to the COPD-related atherothrombotic risk.

Background: Cardiovascular diseases are prevalent in people with chronic obstructive pulmonary disease (COPD). We hypothesized that endothelial dysfunction could be a marker of the proatherogen status in COPD. Methods and results: We measured endothelial dysfunction by flow-mediated dilation (FMD) and after sublingual administration of nitroglycerin (nitrate-mediated dilation: NMD) in 44 COPD patients and 48 controls. Compared with controls COPD patients had worse mean FMD (5.4% vs 8.2%, P < .001) and NMD (12.0% vs 13.9%, P = .007). FMD was inversely related to FEV1/VC ratio ( r = −0.327, P = .030). The negative association between COPD and FMD was confirmed after correction for potential confounders in a multiple linear regression model (β = −0.019, P = .002). In the same model NMD (β = 0.396, P < .001) was positively associated with FMD. Conclusions: Endothelial-dependent and, to a lesser extent, endothelial-independent dilations are significantly impaired in COPD, and the impairment is proportional to the severity of bronchial obstruction.

Portal vein thrombosis (PVT) is observed in 10-20% of patients with liver cirrhosis, which is responsible for 20% of all PVT cases. The main pathogenic factor of PVT in cirrhosis is the obstacle to portal flow, but acquired and inherited clotting abnormalities may play a role. The formation of collateral veins allows many patients to remain asymptomatic and prevents the onset of clinical complications also in patients with totally occlusive PVT. Gastrointestinal bleeding, thrombosis of superior mesenteric vein and refractory ascites are typical manifestations of PVT. Instrumental diagnosis can be obtained by colour-doppler ultrasonography. Future studies should verify whether asymptomatic PVT worsens liver failure, or if its life-threatening complications reduce survival in patients with cirrhosis. Moreover, randomized controlled trials should clarify the potential effectiveness of anticoagulant therapy in the treatment of PVT.

Objective— Atrial fibrillation (AF) is associated with a high incidence of vascular disease that may be related to a prothrombotic and inflammatory state. Soluble CD40 ligand (sCD40L), which stems essentially from platelet activation, possesses inflammatory and prothrombotic properties. The aim of the study was to assess whether sCD40L is a predictor of stroke or myocardial infarction (MI) in patients with nonvalvular AF. Methods and Results— Plasma levels of sCD40L were measured in 231 patients (177 [77%] had permanent or persistent AF, and 54 [23%] had paroxysmal AF). Patients were followed for a mean period of 27.8±8.8 months, and cardiovascular events such as fatal and nonfatal stroke and MI were recorded. AF population was divided in 2 groups according to sCD40L level above or below the median (4.76 ng/mL). The 2 patients’ groups had similar distribution of cardiovascular risk factors, age, gender, medications, or serum C-reactive protein levels. During the follow-up period, vascular events occurred in 6 (2 nonfatal MI and 4 nonfatal ischemic strokes) of 116 patients with low levels of sCD40L (5.1%) and in 29 (11 fatal and 3 nonfatal MI; 3 fatal and 12 nonfatal ischemic strokes) of 115 patients with high levels (25.2%) (log-rank test: P Conclusions— This study shows that enhanced soluble CD40L level is a predictor of vascular events in patients with nonvalvular AF, thus suggesting that enhanced platelet activation may play a role in its clinical progression.

Background. The restrictive, but not the obstructive respiratory dysfunction, is associated with an increased risk of developing type 2 diabetes mellitus. Our aim was to verify in an elderly nondiabetic population whether a restrictive respiratory pattern was associated with a higher prevalence of metabolic syndrome and increased insulin resistance than were obstructive and normal respiratory patterns. Methods. We performed a cross-sectional study of 159 consecutive nondiabetic elderly persons attending two social centers. According to their spirometric pattern, volunteers were classified into the following categories: normal spirometry, obstructive (forced expiratory volume in 1 second/forced vital capacity , 0.70), and restrictive pattern (forced vital capacity , 80% predicted, forced expiratory volume in 1 second/forced vital capacity � 0.70). Independent correlates of the metabolic syndrome were identified. Results. The prevalence of metabolic syndrome was higher in restrictive (56%) than in both normal (21.4%, p ¼.001) and obstructive volunteers (12.9%, p ¼.001). Insulin resistance, as assessed by the log transformation of the HOmeostasis Model Assessment (HOMA), was higher in restrictive than in obstructive and normal volunteers (1 6 0.6 vs 0.3 6 0.6 and 0.5 6 0.5, p , .001). Restriction was an independent correlate of metabolic syndrome, also after adjustment for waist circumference and body mass index (odds ratio ¼ 3.23, 95% confidence interval, 1.23‐8.48; p ¼ .01). Conclusion. Restrictive, but not obstructive respiratory pattern, is associated with metabolic syndrome and insulin resistance, and does not only reflect a limitation of ventilation due to visceral obesity. Metabolic abnormalities likely mediate cardiovascular risk in patients with restrictive respiratory impairment.

The epithelioid hemangioendothelioma of the liver has been recently characterized as a rare tumor with distinctive pathological features affecting young adults. Our report describes a case of histologically confirmed primary epithelioid hemangioendothelioma of the liver, diagnosed by clinical examination as well as radiological (CT/MR) and scintigraphic imaging (labelled red cells/ phytate-SPECT). This case highlights the usefulness of nuclear medicine techniques during the diagnostic of this rare tumor. Further it stresses the possibility of employing an easy and noninvasive method to adequately follow-up those patients who cannot be considered as disease-free even after orthotopic liver transplantation because of the recurrence of the disease in the transplanted liver.

Aim of this study was to analyse the relationship between the plasma levels of polyphenols and the antioxidant activity of red and white wine. Twenty healthy subjects (HS) were randomly allocated to drink 300 ml of red (n = 10) or white n = 10 wine for 15 days. Ten HS who refrained from any alcohol beverage for 15 days were used as control. Urinary PGF-2-III, a marker of oxidative stress and plasma levels of polyphenols were measured. Urinary PGF-2-III significantly fell in subjects taking wine with a higher percentage decrease in subjects given red wine (−38.5 ± 6%, p < 0.001) than in those given white wine (−23.1 ± 6%). Subjects taking red wine had higher plasma polyphenols than those taking white wine (1.9 ± 0.6M versus 1.5 ± 0.33M, p < 0.001). Plasma polyphenols were inversely correlated with urinary PGF2 (r = 0.77, p < 0.001). No changes of urinary isoprostanes were observed in subjects who refrained from wine intake. In vitro study demonstrated that only a mixture of polyphenols, all in a range corresponding to that found in human circulation, inhibited LDL oxidation and PKC-mediated NADPH oxidase activation. Such inhibitory effects were more marked using the concentrations of polyphenols detected in human circulation after red wine intake. This study shows that red wine is more antioxidant than white wine in virtue of its higher content of polyphenols, an effect that may be dependent upon a synergism among polyphenols. © 2005 Elsevier Ireland Ltd. All rights reserved.

D-dimer and factor VIII levels raise in advanced cirrhosis. We investigated the behavior and the diagnostic usefulness of D-dimer and factor VIII in cirrhotic patients with asymptomatic portal venous thrombosis. Factor VIII coagulant and D-dimer values were measured in 136 consecutive outpatients with stable cirrhosis divided according to Child-Pugh (CP) classification, who underwent color/power ultrasonography to detect portal thrombosis. Portal thrombosis was found in 33 patients (24.2%). In patients without thrombosis, factor VIII was significantly higher in CP class C compared with class A and B. Conversely, class C patients with portal thrombosis had lower factor VIII levels than those without thrombosis. In both groups, D-dimer was significantly increased in class C compared with class A and B. In class C, thrombotic patients showed higher D-dimer values than did patients without thrombosis. In class C, a D-dimer valueor = 0.55 microg/mL provided a sensitivity and a negative predictive value for portal thrombosis of 100%, and a factor VIII coagulant levelor = 80% showed a specificity and a negative predictive value of 76% and 84%, respectively. In class B, a D-dimer valueor = 0.225 microg/mL had a sensitivity of 89% and a negative predictive value of 82%. In conclusion, our study shows that factor VIII values increase in severe cirrhosis but significantly decrease in the presence of concomitant portal thrombosis, likely because of consumption during thrombosis; D-dimer is enhanced by both liver failure and portal thrombosis; in severe cirrhosis, normal D-dimer and factor VIII values may safely exclude the presence of asymptomatic portal thrombosis.

Cancer increases the risk for venous thromboembolism (VTE) and patients presenting with a seemingly idiopathic VTE often have an occult cancer. Aging also is a risk factor for VTE. Therefore, old patients with cancer are supposed to be at very high risk for VTE, but inherent data are sporadic and contrasting. We reviewed the literature about the relation between cancer and VTE, with particular attention to findings concerning elderly patients. While aging and postmenopausal status enhance the risk of chemotherapy-induced VTE in women with breast cancer, the rate of a cancer diagnosis in the first year after VTE seems to be even lower in elderly compared to young subjects. Thus, further studies are needed to understand whether or not aging and cancer have additive thrombogenic effects. Finally, we discuss prophylactic and therapeutic strategies.

A 67-year-old man with polycythemia, secondary to chronic obstructive pulmonary disease, had angina attacks at rest treated successfully by supplementing conventional therapy with frequent phlebotomies. Although phlebotomy reduces arterial oxygen content, it also decreases blood viscosity, improves peripheral oxygen consumption and thus yields the clinical benefit.

In order to assess high-pressure barocepture sensitivity and parasympathetic function in elderly patients with silent myocardial ischemia, we selected 45 inpatients in our geriatric unit for a prospective cohort study of patients with coronary heart disease. All patients were over 65 years of age (37 men and 8 women) and had coronary heart disease, documented by an angiographic study and electrocardiographic evidence of myocardial ischemia during exercise stress testing, performed according to the Bruce protocol. The subjects were divided in three subgroups: group 1 (22 patients) with electrocardiographic and echocardiographic history of myocardial infarction but no angina chest pain during exercise testing; group 2 (13 patients) with no exercise induced chest pain; and group 3 (10 patients) with exercise-induced chest pain. Baroceptor sensitivity was assessed in all subjects, by evaluating heart rate changes expressed in RR interval on the basis of changes in the mean arterial pressure during intravenous infusion of stepwise doses (50–100 and 150 μg) of phenylephrine hydrochloride. Heart rate changes were also evaluated during overshoot of the Valsalva maneuver (Valsalva max.), providing an index of parasympathetic activity. Our results showed that group two patients (only silent ischemia) had significantly (P>0.001) greater baroceptor sensitivity than the other two groups (group 2; 15.2±1.9 ms/mmHg; group 1: 10.0±1.7 ms/mmHg; and group 3: 9.8±1.7 ms/mmHg). Group two also showed a significant positive correlation (r=0.58; P

OBJECTIVE: The known association between systemic arterial hypertension in its initial stages and increased sympathetic nervous system drive prompted us to evaluate the influence of age on autonomic nervous system function in subjects with salt-sensitive arterial hypertension. DESIGN: In a randomized study, autonomic nervous system function was assessed by power spectral analysis of heart-rate variability calculated with an autoregressive algorithm in salt-sensitive hypertensives and controls at baseline and under sympathetic stress (passive head-up tilt). For 1 week before the study, all subjects kept to a diet supplying 120 mEq sodium. Sodium sensitivity was assessed by measuring and comparing arterial pressures after a 7-day controlled dietary sodium intake of 20 mEq per day and after a 7-day period on 220 mEq sodium/day. SETTING: Geriatric Division at the I Medical Clinic of the University of Rome “La Sapienza”. PARTICIPANTS: Sixty-five patients with salt-sensitive hypertension (age range 19 to 89 years) and 64 age-matched normotensive controls, divided for data comparison into three age-groups

Hypertension is often associated with findings of sympathetic hyperactivity. Evidence shows that adrenergic receptor stimulation can induce left ventricular hypertrophy. Using an autoregressive algorithm in a power spectrum analysis of heart-rate variability in 14 subjects with mild hypertension (mean age 41 +/- 9.0 years) and 9 age-matched normotensives we compared autonomic nervous system function at baseline (rest) and during sympathetic stress (passive head-up tilt). The spectrum comprised four spectral frequency-domains: total power (0.0033-0.40 Hz), high-frequency power (0.16-0.40 Hz), low-frequency power (0.04-0.15 Hz) and very-low-frequency power (0.0033-0.04). The high-frequency spectral component predominantly reflects vagal activity, the low-frequency component sympathetic nervous system activity. The ratio between low-and high-frequency power expresses the sympathovagal balance. Results were expressed as natural logarithms of power and normalized units. In addition, we compared spectral densities obtained, with the left ventricular mass index evaluated by M-mode echocardiography. Hypertensive subjects had greater low-frequency and low-high frequency ratio values (P < 0.001) than normotensive controls. They also had a low capacity for increase after tilt. Multiple regression analysis showed that the left-ventricular mass index was independently associated with the body mass index (P < 0.0027), very-low frequency (P < 0.043), and low frequency (P < 0.0138) expressed as the natural logarithm, low-high frequency ratio (P < 0.0172) and systolic blood pressure (P < 0.0353). Our findings confirm enhanced sympathetic activity in hypertensive subjects. They also indicate a close association between the left-ventricular mass index and spectral indices of sympathetic activation.