Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia

Sarcopenia, the age-associated loss of skeletal muscle mass and function, has considerable societal consequences for the development of frailty, disability, and health care planning. A group of geriatricians and scientists from academia and industry met in Rome, Italy, on November 18, 2009, to arrive at a consensus definition of sarcopenia. The current consensus definition was approved unanimously by the meeting participants and is as follows: Sarcopenia is defined as the age-associated loss of skeletal muscle mass and function. The causes of sarcopenia are multifactorial and can include disuse, altered endocrine function, chronic diseases, inflammation, insulin resistance, and nutritional deficiencies. Although cachexia may be a component of sarcopenia, the 2 conditions are not the same. The diagnosis of sarcopenia should be considered in all older patients who present with observed declines in physical function, strength, or overall health. Sarcopenia should specifically be considered in patients who are bedridden, cannot independently rise from a chair, or who have a measured gait speed less that 1 m/s(-1). Patients who meet these criteria should further undergo body composition assessment using dual energy x-ray absorptiometry with sarcopenia being defined using currently validated definitions. A diagnosis of sarcopenia is consistent with a gait speed of less than 1 m·s(-1) and an objectively measured low muscle mass (eg, appendicular mass relative to ht(2) that is ≤ 7.23 kg/m(2) in men and ≤ 5.67 kg/m(2) in women). Sarcopenia is a highly prevalent condition in older persons that leads to disability, hospitalization, and death.     

氯菊酯和溴氰菊酯对大鼠血清及脑甲状腺激素水平的影响

目的探讨拟除虫菊酯对大鼠甲状腺激素（TH）水平的影响。方法经口连续１５d给予大鼠氯菊酯（PM）１００、２００、４００mg·kg－１·d－１和溴氰菊酯（DM）６．２５、１２．５０、２５．００mg·kg－１·d－１。用放射免疫分析法检测大鼠血清、脑组织及其亚细胞结构中的TH水平。结果（１）PM：２００、４００mg·kg－１·d－１组大鼠血清三碘甲腺原氨酸（T３）、四碘甲腺原氨酸（T４）、游离T３（fT３）、游离T４（fT４）均下降，而促甲状腺激素（TSH）上升，且现PM呈现剂量依赖关系（T４：r＝０．６７９，fT４：r＝０．５１１，TSH：r＝０．７３８，均P＜０．０１）；１００mg·kg－１·d－１组大鼠T４和fT４下降，T３、fT３、TSH无明显变化。３个处理组大鼠大脑皮层T４分别为（３９．９±５．０）、（３３．４±９．２）、（３２．３±８．２）pg／mgpro，明显低于对照［（４４．２±７．１）g／mgpro］，且有剂量依赖性（r＝０．５２９，P＜０．０１）；而PM染毒４００mg·kg－１·d－１组的T３［（２１．２±５．２）pg／mgpro比对照［（３０．９±１０．０）pg／mgpro］明显降低。２００、４００mg·kg－１·d－１组大鼠海马T４为（１９．１±５．５）、（１９．２±６．５）pg／mgpro，T３为（３     

Determinants of arsenic metabolism: blood arsenic metabolites, plasma folate, cobalamin, and homocysteine concentrations in maternal-newborn pairs

BACKGROUND: In Bangladesh, tens of millions of people have been consuming waterborne arsenic for decades. The extent to which As is transported to the fetus during pregnancy has not been well characterized. OBJECTIVES: We therefore conducted a study of 101 pregnant women who gave birth in Matlab, Bangladesh. METHODS: Maternal and cord blood pairs were collected and concentrations of total As were analyzed for 101 pairs, and As metabolites for 30 pairs. Maternal urinary As metabolites and plasma folate, cobalamin, and homocysteine levels in maternal cord pairs were also measured. Household tube well-water As concentrations exceeded the World Health Organization guideline of 10 microg/L in 38% of the cases. RESULTS: We observed strong associations between maternal and cord blood concentrations of total As (r = 0.93, p < 0.0001). Maternal and cord blood arsenic metabolites (n = 30) were also strongly correlated: in dimethylarsinate (DMA) (r = 0.94, p < 0.0001), monomethylarsonate (r = 0.80, p < 0.0001), arsenite (As(+3)) (r = 0.80, p < 0.0001), and arsenate (As(+5)) (r = 0.89, p < 0.0001). Maternal homocysteine was a strong predictor of %DMA in maternal urine, maternal blood, and cord blood (beta = -6.2, p < 0.02; beta = -10.9, p < 0.04; and beta = -13.7, p < 0.04, respectively). Maternal folate was inversely associated with maternal blood As(5+) (beta = 0.56, p < 0.05), and maternal cobalamin was inversely associated with cord blood As(5+) (beta = -1.2, p < 0.01). CONCLUSIONS: We conclude that exposure to all metabolites of inorganic As occurs in the prenatal period.     

Prognostic markers in resected stage I and II non small-cell lung cancer: an analysis of 260 patients with 5 year follow-up

We performed a retrospective analysis of potential prognostic markers in 260 patients with surgically resected stage I and II non small-cell lung cancer (NSCLC) with a minimum 5-year follow-up. Cox proportional hazard models and Wilcoxon tests were employed to analyze the effect of patient characteristics on survival and disease-free survival (DFS). In the univariate analysis, the following were significant predictors of shorter overall survival: N-stage (N1 vs N0) (p<0.001); T-stage (T2 vs T1) (p<0.001); antigen A (loss vs presence) (p<0.01); cough (present vs absent) (p=0.01); bcl-2 expression (positive vs negative) (p=0.03); age (>63.5 vs <63.5) (p=0.03); mucin (positive vs negative) (p<0.03). The following were significant predictors of shorter DFS: N-stage (p<0.001); T-stage (p=0.001); loss of antigen A (p=0.01); mucin expression (p<0.01); cough (p=0.02); Ki-67 expression (p=0.02) and negative bcl-2 expression (p=0.03). Analysis of survival difference for histologic subtype, degree of differentiation, aneuploidy, %S-phase, codon 12 K-ras mutation, and immunohistochemistry staining for Lewisy, p53, Rb, microvessel count, HER2, E-cadherin and neuroendocrine markers did not reach statistical significance. In multivariate analysis, the following predicted for shorter overall survival: N-stage (p<0.01), antigen A (p=0.01), age (p<0.01), and bcl-2 (p=0.05); and for DFS, N-stage (p<0.01), antigen A (p<0.01), Ki-67 (p=0.03), mucin (p=0.04) and T-stage (p=0.05). Of all the clinical-pathological, proliferative, and biological markers studied, only a few carried independent prognostic significance.     

Impact of hospitalization on blood pressure control in Italy: results from the Italian Group of Pharmacoepidemiology in the Elderly (GIFA)

STUDY OBJECTIVES: To evaluate whether hospitalization affects blood pressure control in hypertensive patients, and to identify factors associated with attainment of adequate blood pressure control and with aggressive pharmacologic treatment. DESIGN: Retrospective study. SETTING: Eighty-one hospitals throughout Italy. PATIENTS: A total of 3,304 patients (59% women, 41% men) with a diagnosis of hypertension and uncontrolled blood pressure values at hospital admission. MEASUREMENTS AND MAIN RESULTS: Patients' blood pressures were surveyed during study periods from 1988-1997. Controlled blood pressure was defined according to the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (systolic < 140 mm Hg, diastolic < 90 mm Hg). Aggressive pharmacologic treatment was defined as an increase in the number of antihypertensive drugs that the patient was receiving at hospital discharge compared with the number of drugs on admission. Adequate blood pressure control was achieved in only 767 (23.2%) patients, but the proportion increased in each subsequent survey Age (odds ratio [OR] for 10-year increase 0.82, 95% confidence interval [CI] 0.76-0.88) and male sex (OR 0.79, 95% CI 0.65-0.94) were associated with reduced likelihood of achieving adequate blood pressure control. In contrast, coronary heart disease (OR 1.38, 95% CI 1.14-1.66), year of survey (1995 vs 1988: OR 1.47, 95% CI 1.19-1.82; 1997 vs 1988: OR 1.27, 95% CI 1.02-1.42), length of hospital stay (medium vs lower tertile OR 1.20, 95% CI 0.96-1.49; higher vs lower tertile OR 1.42, 95% CI 1.13-1.77), and increase in number of antihypertensive drugs prescribed (OR 1.21, 95% CI 1.02-1.42 for one drug increase) were associated with improved blood pressure control. In 1753 (53.1%) patients, the number of antihypertensive drugs increased during their hospital stay. Younger age, fewer drugs on admission, lower comorbidity index, diagnosis of chronic heart failure, lengthy hospital stay, and increasing baseline values of systolic and diastolic blood pressure were associated with aggressive pharmacologic treatment. CONCLUSION: Adequate blood pressure control was achieved in only 25% of patients with hypertension despite a trend toward improvement in recent years. Advanced age was one of the main factors associated with less aggressive pharmacologic treatment and with inadequate blood pressure control.     

The G/A nucleotide change at cDNA position 2494 in the E-cadherin gene (CDH1): analysis in Italian patients.

Current studies are investigating new E-cadherin gene (CDH1) mutations that may be responsible for diffuse gastric cancer susceptibility. Recently, a novel CDH1 germline variant presenting a G/A nucleotide change at cDNA position 2494 has been found in Japanese patients with familial diffuse gastric cancer. The consequent amino acid variation (Val/Met) may alter the binding activity to beta-catenin and the adhesive function of the E-cadherin protein. We have investigated its frequency in Italian cases of sporadic diffuse gastric cancer a well as in healthy controls. Peripheral blood samples were collected from consecutive patients with sporadic, diffuse gastric cancer and from healthy controls in the District of Urbino, Marche Region, Central Italy. After DNA extraction, standard techniques for molecular analyses were used to investigate the 2494 G/A germline nucleotide change in CDH1 cDNA. None of the 48 patients and 48 controls showed the G/A 2494 nucleotide change. Assuming a binomial distribution of the mutation among individuals and the absence of mutations in the 48 patients, the 95% upper bound for the underlying mutation frequency was 7.4%. The novel CDH1 nucleotide change is uncommon in Italian patients with sporadic diffuse gastric cancer. Given these results, further analyses in large population-based studies are not advisable.     

Effect of number of lymph nodes sampled on outcome in patients with stage I non-small-cell lung cancer.

PURPOSE: We postulate that surgical sampling and pathologic evaluation of lymph nodes of surgical specimens from patients with stage I non-small-cell lung cancer (NSCLC) can have an effect on the time to recurrence and survival of these patients. PATIENTS AND METHODS: We analyzed data on 442 patients with stage I NSCLC who were treated with surgical resection and some form of lymph node sampling. Associations between total lymph nodes sampled and disease-free survival (DFS) and overall survival (OS) were investigated. The effect of total lymph node stations sampled and the surgical techniques (random lymph node sampling, systematic sampling [SS], or complete mediastinal lymph node dissection [MLND]) on DFS and OS was also studied. Complete MLND and SS were defined as dissection or sampling of levels 4, 7, and 10 for right-sided lesions and levels 5 or 6 and 7 for left-sided lesions. RESULTS: Patients were divided into quartiles on the basis of total number of lymph nodes sampled. Improved DFS and OS were associated with greater number of lymph nodes sampled. SS and MLND were associated with improved survival compared with random lymph node sampling. The total number of lymph nodes sampled maintained strong significance in the multivariate analysis. CONCLUSION: These results indicate that examining a greater number of lymph nodes in patients with stage I NSCLC treated with resection increases the likelihood of proper staging and affects patient outcome. Such information is important not only for therapy and prognosis of individuals but also for identifying those who may benefit from adjuvant therapy.     

Weekly gemcitabine and cisplatin chemotherapy: a well-tolerated but ineffective chemotherapeutic regimen in advanced pancreatic cancer patients. A report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).

BACKGROUND: This phase II study was initiated to determine the activity and toxicity of a combination of gemcitabine (GEM) and cisplatin (CDDP) in patients with pancreatic cancer. PATIENTS AND METHODS: CDDP 35 mg/m(2) was given as a 30-min infusion and GEM 1000 mg/m(2) as a 30-min infusion. Both drugs were administered once weekly for 2 consecutive weeks out of every 3 weeks to chemonaive patients with locally advanced or metastatic pancreatic cancer. RESULTS: Forty-five advanced pancreatic cancer patients received this regimen for a total of 180 cycles of chemotherapy. One complete and four partial responses have been observed for an overall response rate of 9% (95% confidence interval 10% to 11%). Twenty-one patients (46%) had stable disease and 19 progressed on therapy. The median time to progression was 3.6 months, with a median survival of 5.6 months. A clinical benefit was obtained in nine of 37 patients (24%). Side-effects were mainly represented by hematological toxicity. Grade 3/4 WHO toxicities included neutropenia (6% of the patients) and thrombocytopenia (11%). The dose of GEM and CDDP was reduced in 14 patients (31%) and treatment was delayed in 10 patients (22%). CONCLUSIONS: Our results in terms of response rate, clinical benefit and survival do not support an advantage for the combination of GEM and CDDP given by this schedule.     

In a prospective observational study, influenza vaccination prevented hospitalization among older home care patients

OBJECTIVE: The aim of the study is (1) to describe the prevalence of vaccination against influenza in older home care patients and (2) to investigate the protective effect of influenza vaccination for hospitalization events. STUDY DESIGN AND SETTING: This is an observational study conducted in four large cohorts of elderly patients in home care during the 1998-1999, 1999-2000, 2000-2001, and 2001-2002 influenza seasons. We analyzed data from the Italian Silver Network Home Care project. A total of 2,201 patients were enrolled in the present study. The main outcome measures were prevalence of vaccination against influenza and the rate of hospitalization according to vaccination status and influenza season. RESULTS: The rate of influenza vaccination was around 48% of the studied sample. During the follow-up including the peak of influenza and the total influenza season, 412 subjects (40%) were hospitalized among vaccinated compared to 610 subjects (59%) among not vaccinated (P<0.001). After adjusting for age, gender, location of home care program, and all the variables significantly different between vaccinated and not-vaccinated subjects, vaccinated subjects were less likely to be hospitalized compared to not-vaccinated subjects (OR, 0.73; 95% CI 0.60-0.90). CONCLUSIONS: Vaccination against influenza has an important prognostic implication for frail geriatric patients living in the community.     

The role of 5-fluorouracil (5-FU) reintroduction with irinotecan or oxaliplatin in truly 5-FU-refractory advanced colorectal cancer patients

OBJECTIVES: Although several evidences have demonstrated a synergistic activity of 5-fluorouracil with irinotecan and oxaliplatin, thus explaining the use of this drug combination in the first-line treatment of advanced colorectal cancer, the need for the reintroduction of 5-FU in the second-line setting is more questionable. METHODS: We retrospectively evaluated the outcome of patients developing progressive disease while on an infusional 5-FU-based front-line chemotherapy and subsequently treated with one of the four following chemotherapy regimens: irinotecan, oxaliplatin and irinotecan or oxaliplatin both combined with the de Gramont schedule (LV5-FU2). RESULTS: 225 patients (137 males and 88 females), were eligible for analysis. Second-line chemotherapy consisted of irinotecan in 79 patients (35%, group A), oxaliplatin in 47 patients (21%, group B), irinotecan with LV5-FU2 in 53 patients (24%, group C) and oxaliplatin with LV5-FU2 in the remaining 46 cases (20%, group D). The response rate to second-line chemotherapy was obtained in 6/79 patients (8%) in group A, in 4/47 patients (9%) in group B, in 11/53 patients (21%) in group C and in 10/46 patients (22%) in group D (p = 0.04). CONCLUSIONS: These data suggest that reintroduction of 5-FU could increase irinotecan and oxaliplatin activity in patients progressing during a 5-FU-based first-line chemotherapy.