Ferran Masanés

Inhibition of circulating immune cell activation: a molecular antiinflammatory effect of the Mediterranean diet

BACKGROUND Adherence to the Mediterranean diet (Med-Diet) is associated with a reduced risk of cardiovascular disease (CVD). However, the molecular mechanisms involved are not fully understood. OBJECTIVE The objective was to compare the effects of 2 Med-Diets with those of a low-fat diet on immune cell activation and soluble inflammatory biomarkers related to atherogenesis in subjects at high risk of CVD. DESIGN In a controlled study, we randomly assigned 112 older subjects with diabetes or > or =3 CVD risk factors to 3 dietary intervention groups: Med-Diet with supplemental virgin olive oil (VOO), Med-Diet with supplemental nuts, and low-fat diet. Changes from baseline in cellular and serum inflammatory biomarkers were assessed at 3 mo. RESULTS One hundred six participants (43% women; average age: 68 y) completed the study. At 3 mo, monocyte expression of CD49d, an adhesion molecule crucial for leukocyte homing, and of CD40, a proinflammatory ligand, decreased (P < 0.05) after both Med-Diets but not after the low-fat diet. Serum interleukin-6 and soluble intercellular adhesion molecule-1, inflammatory mediators crucial in firm adhesion of leukocytes to endothelial surfaces, decreased (P < 0.05) in both Med-Diet groups. Soluble vascular cellular adhesion molecule-1 and C-reactive protein decreased only after the Med-Diet with VOO (P < 0.05), whereas interleukin-6, soluble vascular cellular adhesion molecule-1, and soluble intercellular adhesion molecule-1 increased (P < 0.05) after the low-fat diet. CONCLUSIONS Med-Diets supplemented with VOO or nuts down-regulate cellular and circulating inflammatory biomarkers related to atherogenesis in subjects at high risk of CVD. The results support the recommendation of the Med-Diet as a useful tool against CVD.

Functional status and quality of life 12 months after discharge from a medical ICU in healthy elderly patients: a prospective observational study

IntroductionLong-term outcomes of elderly patients after medical ICU care are little known. The aim of the study was to evaluate functional status and quality of life of elderly patients 12 months after discharge from a medical ICU.MethodsWe prospectively studied 112/230 healthy elderly patients (≥65 years surviving at least 12 months after ICU discharge) with full functional autonomy without cognitive impairment prior to ICU entry. The main diagnoses at admission using the Acute Physiology and Chronic Health Evaluation III (APACHE III) classification diagnosis and length of ICU stay and ICU scores (APACHE II, Sepsis-related Organ Failure Assessment (SOFA) and OMEGA) at admission and discharge were collected. Comprehensive geriatric assessment included the presence of the main geriatric syndromes and the application of Lawton, Barthel, and Charlson Indexes and Informant Questionnaire on Cognitive Decline to evaluate functionality, comorbidity and cognitive status, respectively. The EuroQol-5D assessed quality of life. Data were collected at baseline, during ICU and ward stay and 3, 6 and 12 months after hospital discharge. Paired or unpaired T-tests compared differences between groups (continuous variables), whereas the chi-square and Fisher exact tests were used for comparing dichotomous variables. For variables significant (P ≤ 0.1) on univariate analysis, a forward multiple regression analysis was performed.ResultsOnly 48.9% of patients (mean age: 73.4 ± 5.5 years) were alive 12 months after discharge showing a significant decrease in functional autonomy (Lawton and Barthel Indexes) and quality of life (EuroQol-5D) compared to baseline status (P < 0.001, all). Multivariate analysis showed a higher Barthel Index and EQ-5D vas at hospital discharge to be associated factors of full functional recovery (P < 0.01, both). Thus, in patients with a Barthel Index ≥ 60 or EQ-5D vas ≥40 at discharge the hazard ratio for full functional recovery was 4.04 (95% CI: 1.58 to 10.33; P = 0.005) and 6.1 (95% CI: 1.9 to 19.9; P < 0.01), respectively. Geriatric syndromes increased after ICU stay and remained significantly increased during follow-up (P < 0.001).ConclusionsThe survival rate of elderly medical patients 12 months after discharge from the ICU is low (49%), although functional status and quality of life remained similar to baseline in most of the survivors. However, there was a two-fold increase in the prevalence of geriatric syndromes.

Valoración de la capacidad funcional después de un ingreso hospitalario en pacientes nonagenarios

Fundamento Despues de un ingreso hospita-lario puede existir una perdida en la capaci-dad funcional, posiblemente mas importan-te en las personas mas ancianas. Pacientes y metodo Se estudio de manera prospectiva a 125 pacientes nonagenarios ingresados en los hospitales de Bellvitge y Clinic de Barcelona, y se realizo un control a los 3 meses. Resultados Veinticuatro pacientes (19%) fa-llecieron durante el ingreso. En los 101 res-tantes la media del indice de Barthel (IB) previo fue de 75, al ingreso 33 (p Conclusiones En los pacientes nonagenarios despues de una hospitalizacion se produce una alteracion funcional que persiste a los 3 meses del alta.

Skeletal muscle studies in patients with HIV-related wasting syndrome

Previous reports have suggested that HIV-related wasting syndrome may be considered as a form of myopathy. The aim of the present study was to investigate histopathological muscle changes in HIV-related wasting syndrome in order to know if there is a common substrate and whether muscle plays a primary or secondary role in its development. Patients with wasting syndrome diagnosed by Centers for Disease Control (CDC) criteria were prospectively evaluated. Clinical, analytical, nutritional, anthropometrical and muscular data were recorded. The patients were subdivided into two groups: group A was constituted by patients in whom wasting syndrome was the AIDS-defining illness, and group B by patients in whom AIDS diagnosis was previously made. In all cases muscle biopsy was performed and processed for conventional stainings and histochemical reactions. Thirty patients were included (group A, 12; group B, 18). Clinical, analytical, nutritional and anthropometrical data did not essentially differ between the two groups. All patients were malnourished with respect to controls. Histopathological findings in muscle biopsy were heterogeneous and similar in both groups, except for HIV-related myopathies, which were more frequently seen in the patients from group A (P=0.05). In five cases (17%) an unsuspected and potentially treatable myopathy was diagnosed. Patients with polyarteritis nodosa (two) or polymyositis (one) were treated with prednisone, which improved their wasting syndrome. By contrast, patients with AZT-myopathy (two) did not improve when the drug was discontinued. We conclude that in most cases the wasting syndrome cannot be considered as a true myopathy, and probably metabolic and/or nutritional factors may account for wasting development. However, in a subset of patients muscle biopsy allows the diagnosis of a treatable myopathy leading to the improvement of wasting syndrome.

Clinical, histological and molecular reversibility of zidovudine myopathy.

The use of zidovudine in the treatment of human immunodeficiency virus infection has been associated with toxic mitochondrial myopathy. There are some reported cases of improvement after stopping the drug, but in only one were molecular studies performed. We therefore studied three patients with toxic AZT myopathy during AZT treatment and after drug withdrawal. Clinical complaints disappeared within the next three months after drug cessation. In all cases, histological data of mitochondrial abnormalities also disappeared. Molecular studies showed an initial depletion of the total amount of mitochondrial DNA with respect to healthy controls which was reversible after AZT withdrawal. This work demonstrates that AZT myopathy is reversible not only at a clinical and histological, but also at a molecular level.

Prophylaxis of Gastrointestinal Tract Bleeding with Magaldrate in Patients Admitted to a General Hospital Ward

A randomized, placebo-controlled trial was performed to assess the effect of magaldrate (800 mg every 4 h) in reducing the rate of upper gastrointestinal tract bleeding among 100 consecutive patients with severe diseases admitted to a general hospital ward. Upper gastrointestinal tract bleeding occurred in 11 of 48 placebo-treated patients and in only 1 of 52 magaldrate-treated patients (p less than 0.01). Endoscopic examination of these patients showed gastric ulcer (two cases), multiple gastric mucosa ulcerations (nine), and no lesions (one). In three patients who received placebo the hemorrhage was clinically relevant and required transfusion of two or more blood units. Patients with two or more risk factors showed a higher rate of gastrointestinal hemorrhage (p less than 0.05). Respiratory failure and treatment with a high dose of corticosteroids were associated with the highest incidence of bleeding (p less than 0.05 for both). The only adverse reaction associated with magaldrate was a mild and self-limiting diarrhea in two cases. We conclude that patients seriously ill admitted to a general hospital ward should be treated with a prophylactic agent against stress-induced ulcer bleeding. Magaldrate is an effective and safe antacid to prevent gastrointestinal tract bleeding in such patients.

Natural history of functional decline 1 year after hospital discharge in nonagenarian patients

To the Editor: The use of hospital care increases significantly with age, especially by extremely elderly patients such as nonagenarians. 1,2 Almost one-third of older adults hospitalized for acute medical illness decline in their ability to perform basic activities of daily living (ADLs) at discharge. 3 Rate of functional decline may be higher in oldold patients, 4 and this decline in ADLs related to hospitalization may persist 3 months later and in many patients 1 year after discharge. 2,5 We investigated the consequences of hospitalization on the nonagenarian patient’s functional capacity and the requirements of institutionalization in the first year after hospital discharge. A prospective longitudinal study was performed, focusing on 300 consecutive nonagenarian patients admitted to the hospital from the emergency department of two university hospitals during 2000. Exclusion criteria were hospital discharge (n 63) or death (n 27) in the first 72 hours of admission, patients admitted because of palliative care treatment (n 11), patients completely impaired in all ADLs (n 10), or patients with a cognitive or communication impairment in the absence of a caregiver (n 7). The admission assessment included baseline demographic information including current living situation. Functional status was assessed using the Barthel Index (BI). 6 Charlson Comorbidity Score (CCS) was used to measure comorbidity. 7 The office of Population Censuses and Surveys was contacted when the patient was not found to confirm their status. The results were analyzed using conventional descriptive statistics (chi-square test, paired t test, and one-way analysis of variance). All statistical tests were two-sided, with P .05 as the criterion to indicate statistical significance. One hundred eighty-two patients were included; 123 were women (67%), and their mean age was 92.3. The majority (80%) were widowed, 13% were married, and 7% were single. Mean hospitalization stay was 11.7 days. Ninety percent of patients lived at home before admission. Table 1 shows the main admission diagnoses. Mean BI previous to admission was 72; 26 patients (14%) maintained complete independence in ADLs (BI 100), and 93 patients (51%) had a BI superior to 79. The mean standard deviation CCS was 1.8 0.4. In-hospital mortality was 20%. In 83 patients, the scheduled follow-up was not possible 1 year after discharge; 52 had died, nine were lost to follow-up, and 21 had a hospital readmission. The mean BI of the remaining surviving 64 patients after 1 year of hospital admission was 67, significantly higher than their BI at discharge (52; P .001), although lower than before admission (81; P .001). The BI after 1 year was similar to that at 3-month follow-up (69; P .7). Seventy-nine percent of patients had similar BI at 3-month and 12-month follow-up. A decline in BI persisted in 64% of patients, and only 23 patients (36%) returned to their previous ability. Total mortality rate was 48%. Eleven percent of the patients could not return to their preadmission dwelling. These results, as supported by previous data from other studies about the oldest-old, indicate that the majority are women, usually widowed, and living at home. 8 A remarkably low prevalence of institutionalization (10%) previous to admission was found. Many nonagenarians are functionally independent despite their advanced age. 1 More than 50% of our patients had good functional status before admission. The functional decline after hospitalization has a multifactorial, interactive, cumulative etiology, 5 and often disability persists 12 months later. 9 The loss of functional capacity in our population after 1 year of hospital admission is important. The declines in functionality may be the cumulative result of the failure to recover and an additional functional losses. 3 Although the effect of a new hospitalization was excluded, only 36% of the patients maintained their previous BI 1 year later. In these patients, this functional decline showed a tendency to recover at 3month follow-up, but BI did not increase further in most of them during the period analyzed. Even though this decline in ADLs occurred, as previously reported, 2,10 most hospitalized nonagenarians returned to their previous living conditions after discharge. The high rate of mortality in this elderly population with a limiting heterogeneity of diagnosis may be due to high frailty of nonagenarians after any hospital admission. Acute care hospitals must adopt methods to implement approaches to prevent the persistent loss in ability to perform ADLs observed in hospitalized elderly. Alternative Table 1. Distribution of the Main Diagnoses at Admission of the 182 Nonagenarian Patients Included in the Study

Prevalence of sarcopenia in patients attending outpatient geriatric clinics: the ELLI study

OBJECTIVES the aim of this study is to know the prevalence of sarcopenia in geriatric outpatient clinics using the EGWSOP (European Working Group on Sarcopenia in Older People) diagnostic criteria that include muscle mass, muscle strength and physical performance. METHODS subjects over 69 years old, able to walk without help and who attended five geriatric outpatient clinics were recruited. Body composition was assessed using bioimpedance analysis (BIA), grip strength using a JAMAR dynamometer and physical performance by the 4 m gait speed. Sarcopenia was diagnosed using the EGWSOP criteria (gait speed <0.8 m/s; grip strength <30 kg in men or <20 kg in women, and muscle mass index (MMI) <8.31 kg/m(2) in men or <6.68 kg/m(2) in women). RESULTS two hundred and ninety-eight subjects were included (median age 83.2 years, 63.1% women). 19.1% had sarcopenia (12.7% men, 22.9% women); 20.1% had low muscle mass; 68.8% had low gait speed and 81.2% low grip strength. Only 21.9% of the subjects with low grip strength and 19.5% of those with low gait speed had sarcopenia. No correlations between muscle mass and either muscle strength or gait speed were detected. CONCLUSIONS sarcopenia is present in one out of five subjects attending geriatric outpatient clinics.

Cut-off points for muscle mass — not grip strength or gait speed — determine variations in sarcopenia prevalence

OBJECTIVES To study the importance of weight change with regard to mortality in older people. DESIGN Prospective cohort study. PARTICIPANTS The cohort includes participants in the Hordaland Health Study, Norway, 1997-99 (N=2935, age 71-74 years) who had previously participated in a survey in 1992-93. MEASUREMENTS Participants with weight measured at both surveys were followed for mortality through 2012. Cox proportional hazards models were used to calculate risk of death according to changes in weight. Hazard ratios (HR) with 95% confidence intervals (CIs) for people with stable weight (± <5% weight change) were compared to people who lost (≥5%) or gained (≥5%) weight. Cox regression with penalized spline was used to evaluate the association between weight change (in kg) and mortality. Analyses were adjusted for age, sex, physical activity, smoking, diabetes, hypertension, and previous myocardial infarction or stroke. Participants with cancer were excluded. RESULTS Compared to those with stable weight, participants who lost ≥5% weight had an increased mortality risk (HR 1.59 [95% CI: 1.35-1.89]) while the group with weight gain ≥5% did not (HR 1.07 [95% CI 0.90-1.28]). Penalized spline identified those who lost more than about three kg or gained more than about 12 kg as having increased risk of death. CONCLUSION Even a minor weight loss of ≥5% or >3 kg were significantly associated with increased risk of mortality. Thus, weight should be routinely measured in older adults.ObjectivesThe European Working Group on Sarcopenia in Older People (EWGSOP) has proposed different methods and cut-off points for the three parameters that define sarcopenia: muscle mass, muscle strength and physical performance. Although this facilitates clinical practice, it limits comparability between studies and leads to wide differences in published prevalence rates. The aim of this study was to assess how changes in cut-off points for muscle mass, gait speed and grip strength affected sarcopenia prevalence according to EWGSOP criteria.MethodsCross-sectional analysis of elderly individuals recruited from outpatient clinics (n=298) and nursing homes (n=276). We measured muscle mass, grip strength and gait speed and assessed how changes in cut-off points changed sarcopenia prevalence in both populations.ResultsAn increase from 5.45 kg/m2 to 6.68 kg/m2 in the muscle mass index for female outpatients and nursing-home residents increased sarcopenia prevalence from 4% to 23% and from 9% to 47%, respectively; for men, for an increase from 7.25 kg/m2 to 8.87 kg/m2, the corresponding increases were from 1% to 22% and from 6% to 41%, respectively. Changes in gait speed and grip strength had a limited impact on sarcopenia prevalence.ConclusionThe cut-off points used for muscle mass affect the reported prevalence rates for sarcopenia and, in turn, affect comparability between studies. The main factors influencing the magnitude of the change are muscle mass index distribution in the population and the absolute value of the cut-off points: the same difference between two references (e.g., 7.5 kg/m2 to 7.75 kg/m2 or 7.75 kg/m2 to 8 kg/m2) may produce different changes in prevalence. Changes in cut-off points for gait speed and grip strength had a limited impact on sarcopenia prevalence and on study comparability.

Prevalencia de sarcopenia en consultas de geriatría y residencias: estudio ELLI

BACKGROUND There are few systematic studies on the prevalence of sarcopenia using the new diagnostic criteria in different geriatric care settings. OBJECTIVE To estimate the prevalence of sarcopenia, using the European Working Group on Sarcopenia in Older People (EWGSOP) criteria in older subjects living in nursing homes and in those who attend geriatric outpatient clinics. MATERIAL AND METHODS A single country multicentre study in two samples of older subjects: patients cared for in outpatient geriatric clinics, and individuals living in nursing homes. Data collected will include demographic variables, medical history, medication, geriatric syndromes, functional status (assessment of basic and instrumental activities of daily living), mobility, cognitive status, comorbidity, quality of life, nutritional status, and laboratory parameters. For the diagnosis of sarcopenia, 4m walking speed, handgrip strength, and body composition measured by bioelectrical impedance analysis will be assessed. RESULTS Using the EWGSOP algorithm, the prevalence of sarcopenia in an elderly Spanish population will be estimated. In addition, concordance and correlation between the three parameters included in the definition (muscle mass, muscle strength, and physical performance) will be analysed, using the different existing cut-off points, and examining the diagnostic accuracy of each. Finally, demographic, anthropometric and functional data that define subjects with sarcopenia will be investigated. CONCLUSIONS The ELLI study should improve knowledge on the prevalence and characteristics of sarcopenia in older people in our population.