Screening for frailty in elderly emergency department patients by using the Identification of Seniors At Risk (ISAR).

OBJECTIVES: Frail older adults are at an increased risk for adverse outcomes after an Emergency Department (ED) visit. Comprehensive geriatric assessment (CGA) has been proposed to screen for frailty in the ED, but it is difficult to carry out. We tested whether a CGA-based approach using the Identification of Seniors At Risk (ISAR) screening tool was associated with the brief deficit accumulation index (DAI) of frailty. DESIGN: Prospective observational study. SETTING: Two urban EDs in Italy. PARTICIPANTS: A cohort of 200 elderly (≥65 years) ED patients. MEASUREMENTS: Identifiers, triage, clinical and social data along with the administration of ISAR. CGA was performed using: Charlson Index, Short Portable Mental Status Questionnaire and Katz's ADL. Follow-up data at 30 and 180 days included: mortality, ED revisit, hospital admission, and functional decline. Frailty was defined according to a brief DAI. Logistic regression evaluated the consistency of the frailty definition; ROC curves evaluated ISAR ability in identifying frailty. RESULTS: Frailty was present in 117 (58.5%) subjects and predicted ED revisit and frequent ED return, hospitalization and 6-month mortality. ISAR had an AUC of 0.92 (95%CI 0.88-0.96, p<0.0001) in identifying frail elders in the ED and using a cut-off of 2 showed 94% sensitivity and 63% specificity. CONCLUSION: ISAR is a useful screening tool for frailty and identifies elderly patients at risk of adverse outcomes after an ED visit. ISAR can also be used to select high-risk patients more likely to benefit from a geriatric approach or intervention, independently of admission or discharge.

Dietary determinants of colorectal proliferation in the normal mucosa of subjects with previous colon adenomas.

Dietary determinants of colorectal mucosa proliferation were studied in 69 subjects previously operated for at least two sporadic colon adenomas. Information on recent dietary habits was collected by a validated food frequency questionnaire, and proliferation was measured by [3H]thymidine incorporation in colorectal biopsies by determining the labeling index (LI) and the percentage of LI in the upper part of the crypt, two parameters that are increased in subjects at high risk of colon cancer. The LI was significantly higher in women as compared with men (P = 0.01). Diet showed several associations with colorectal mucosa proliferation: (a) subjects in the highest tertile of fish consumption had a significantly lower LI (P = 0.0013) compared with those in the lower tertiles [5.20 +/- 1.87 versus 6.80 +/- 2.18 (mean +/- SD)]; (b) subjects with a low red meat consumption had lower proliferation in the upper part of the crypt [2.38 +/- 2.10, 5.30 +/- 4.62, and 5.89 +/- 4.82 in the low, middle, and high tertile of consumption, respectively (mean +/- SD); P = 0.0093]; (c) according to estimated nutrient intakes, the LI was lower in subjects reporting a high intake of starch (P = 0.006) and higher in subjects with a low intake of beta-carotene (P = 0.002). The results show that subjects reporting a diet rich in fish, starch, and beta-carotene and low in red meat had lower colorectal mucosa proliferation and a normal pattern of proliferation along the crypt. Given the correlation between colorectal proliferative activity and colon cancer risk, such a dietary pattern might be beneficial for subjects at high risk of colon cancer.

Slow-release pellets of sodium butyrate increase apoptosis in the colon of rats treated with azoxymethane, without affecting aberrant crypt foci and colonic proliferation.

We investigated whether sodium butyrate, administered orally as gastroresistant slow-release pellets to rats, could affect markers of colon carcinogenesis. F344 male rats were fed a high-fat diet (230 g/kg corn oil, wt/wt) and treated with two injections (1 wk apart) of azoxymethane (15 mg/kg sc) or saline. Rats were then divided into two groups: one received the diet with 1.5% (wt/wt) sodium butyrate for 10 weeks to provide 150 mg butyrate/day, and one group received no butyrate. At the end of this period, rats were sacrificed, and colonic proliferative activity, number of aberrant crypt foci (ACF), and apoptosis were assessed in the colon. The proliferative activity and ACF induction were not affected by butyrate pellet administration. On the contrary, in rats treated with butyrate, apoptotic index increased from 0.12 +/- 0.12 to 0.81 +/- 0.10 (means +/- SE, p < 0.05). The short-chain fatty acid concentration was significantly increased in the feces of rats treated with butyrate. In conclusion, the increase in the mucosal apoptotic index suggests that gastroresistant butyrate pellets have a beneficial effect against colon carcinogenesis. However, because butyrate pellets did not modify proliferation or ACF induction, this conclusion should be confirmed in long-term carcinogenesis experiments.

A dietary trial with a short-term low-sucrose diet in an Italian population: effects on colorectal mucosal proliferation.

Colorectal mucosal proliferation is supposed to predict colon cancer risk. We investigated whether a low-sucrose diet might reduce colorectal mucosal proliferation in a group of patients at higher risk of colorectal cancer after at least two colon adenoma resections. In a pilot phase, 14 patients [12 men and 2 women, 60.3 +/- 5 (SD) yr] were instructed to adopt a low-sucrose diet for one month. Colorectal biopsies were taken twice in the same patients, at the start and the end of the intervention period, and mucosal proliferation was measured by [3H]thymidine uptake in vitro and autoradiography. Although compliance of study participants to dietary modification was high, only a few agreed to two consecutive endoscopies; thus we carried out a randomized study, and 107 patients were assigned to a low-sucrose diet (50 treated patients: 31 men and 19 women, 59.7 +/- 7.5 yr) or instructed to continue their usual diet for one month (55 control patients: 32 men and 23 women, 59.6 +/- 7.7 yr). At the end of this period, colorectal biopsies were obtained. The results of the pilot phase and the randomized study showed that a low-sucrose diet for one-month did not affect proliferation or the distribution of proliferation activity along the crypt. The food-frequency questionnaires indicated that treated patients consumed significantly less sucrose (and fewer total calories) during the dietary modification. Urinary fructose, a measure of dietary sucrose intake, was also reduced at the end of the intervention period. In conclusion, we found no evidence that a low-sucrose diet for one month influences colorectal mucosal proliferation.

Dietary sucrose and starch affect dysplastic characteristics in carcinogen-induced aberrant crypt foci in rat colon.

To study whether dietary carbohydrates affect dysplasia in aberrant crypt foci (ACF), rats treated with 1,2-dimethilhydrazine (DMH) were fed for three months with diets containing 46% sucrose or corn starch. The number of ACF/colon in the two dietary groups was similar (P = 0.58), but ACF were smaller in the starch than in sucrose group (P < 0.05). ACF in the starch group also showed less severe goblet cell dysplasia, more sulphomucins and less sialomucins than in the sucrose group (P < 0.05), indicating that corn starch protects against colon carcinogenesis while sucrose in the diet is detrimental, promoting the dysplasia of preneoplastic lesions like ACF.

Aberrant crypt foci in human colon carcinogenesis.

We developed a procedure for the endoscopic visualization in humans of aberrant crypt foci (ACF), preneoplastic lesions of the colon mucosa, and we determined the frequency of ACF in resected sections of human colon. For the endoscopy we studied 12 consenting adults (6 controls and 6 colon cancer cases) by dyeing colon mucosa with 0.5% methylene blue and searching ACF with a magnifying endoscope. ACF of varying dimensions were visualized in all subjects. We also studied colon surgical specimens from patients with colon cancer or diverticulitis. After staining the mucosa with 2% methylene blue, we found approximately the same density of ACF in the colon mucosa of the patients with colon cancer as in that of patients with diverticulitis (ACF/cm2 were 0.124 +/- 0.143 [N = 14] and 0.108 +/- 0.210 [N = 4], respectively [mean +/- SD]). In conclusion, the visualization of ACF with methylene blue in humans does not identify groups at low and high risk of colon cancer.

Modification of azoxymethane intestinal carcinogenesis in rats by feeding sucrose boluses, pasta, and glucose.

We studied whether repeated boluses of sucrose or diets containing carbohydrates with a variable glycemic index (GI) affect intestinal carcinogenesis in rats. Male F344 rats were treated twice (1 wk apart) with 15 mg/kg sc azoxymethane (AOM) and then divided into four experimental dietary groups with different carbohydrate composition and administration schedules: the sucrose group was fed 44% (wt/wt) sucrose (GI = 65), the bolus group was fed sucrose as carbohydrate and 43 boluses of sucrose (10-15 g/kg) at various time intervals, the pasta group was fed pasta [77% (wt/wt) cooked pasta, GI = 55], and the glucose group was fed 44% (wt/wt) glucose (GI = 97). All nutrients, including carbohydrates, were provided in similar amount to the different groups. The experiment was terminated between Day 230 and Day 245 after AOM administration. At this time the pasta group had significantly higher cecal short-chain fatty acids than the other groups. Intestinal adenomas and cancers occurred with the same frequency in the bolus, sucrose, and glucose groups. On the contrary, we observed a significant decrease (p = 0.03) in the cumulative incidence of intestinal adenomas, but not adenocarcinomas, in the pasta group compared with the sucrose group (intestinal adenoma incidence in the pasta group was 31% compared with 63% in the sucrose group, 46% in the bolus group, and 37% in the glucose group). In conclusion, these results do not support the hypothesis that sucrose boluses or carbohydrates with a high GI stimulate colon carcinogenesis, but they indicate that foods such as pasta may exert a protective effect.

Urinary excretion of sucrose and fructose as a predictor of sucrose intake in dietary intervention studies.

The urinary excretion of sucrose, glucose, and fructose was measured in 9 healthy subjects consuming a common Italian diet and after 3 days of a low sucrose diet, in which the intake of sucrose was restricted but the other main nutrients were unmodified. After the low sucrose diet, we observed a significant drop in the average urinary excretion of sucrose, glucose, and fructose determined at four different times (8:00 and 10:00 a.m.; 3:00 and 10:00 p.m.). The average urinary excretion of fructose in the four urine samples was significantly correlated with dietary sucrose intake. We also found a significant correlation between the average urinary excretion of sucrose and dietary sucrose intake. Urinary fructose can be used as a marker of sucrose intake in dietary intervention studies aimed at studying the effect of variation of carbohydrate intake on specific cancers.

Dietary sucrose, glucose, fructose, and starches affect colonic functions in rats.

To study the effect of dietary sugars and starches on parameters linked to colon carcinogenesis, female Sprague-Dawley rats were fed for one month five different diets containing sucrose, glucose, fructose, cornstarch, or Hylon 7, a starch with a high amylose content. After this period, colon proliferation, assessed by [3H] thymidine incorporation in vitro, was higher (p < 0.05) in rats fed sucrose than in rats fed glucose, fructose, or cornstarch [labeling index was 7.17 +/- 0.75, 5.03 +/- 0.07, 4.55 +/- 0.72, 4.00 +/- 0.70, and 5.89 +/- 1.05 (SE) in sucrose, glucose, fructose, cornstarch, and Hylon 7 diets, respectively]. Cecal pH was lower in rats fed cornstarch and Hylon 7 than in rats fed sucrose, glucose, or fructose. Content of short-chain fatty acids (SCFAs) in the cecum was higher in rats fed Hylon 7 than in those fed glucose and fructose. In conclusion, glucose and fructose, compared with sucrose, decrease mucosal proliferation and may be considered protective factors in colon carcinogenesis, although they do not affect SCFA production and cecal pH. On the contrary, Hylon 7 does not change mucosal proliferation but increases SCFAs and lowers cecal pH, two conditions associated with a lower risk of colon cancer.

Effects of repeated boluses of sucrose on proliferation and on AOM-induced aberrant crypt foci in rat colon.

Colonic mucosal proliferation, aberrant crypt foci (ACF) induction, and fecal bile acids, parameters connected to the risk of colon cancer development, were studied in female F344 rats treated with starch or sucrose boluses or with a sucrose diet. Cell proliferation was higher in animals treated with a single sucrose bolus than in those given a starch bolus (15 g/kg body wt), with 4.3 +/- 0.64 and 2.17 +/- 0.57 (SE) mitotic figures (MF) per crypt in the sucrose and starch bolus groups, respectively (p < 0.01). When azoxymethane (AOM, 20 mg/kg) was administered 24 hours after a single sucrose or starch bolus, the number of ACF per colon after 30 days was higher in the sucrose bolus group [107.5 +/- 9.5 (SE)] than in the starch bolus group (67.8 +/- 0.9, p < 0.01). In additional experiments, colon cell proliferation (MF/crypt) was higher in rats given boluses of sucrose three times per week for 40 days after AOM (20 mg/kg) [5.9 +/- 0.7 (SE)] than in rats given starch boluses (2.96 +/- 0.4) or fed sucrose continuously (3.6 +/- 0.5). On the contrary, after 40 days of dietary treatment, the number, dimension, and percentage of ACF secreting sulfomucins and sialomucins were not varied among these three groups. However, the percentage of "large ACF" (ACF with > or = 4 crypts) secreting sialomucins or predominantly sialomucins was higher (p < 0.05) in the sucrose bolus group than in the starch group. The concentration of fecal bile acids and long-chain fatty acids was the same in the sucrose and starch groups, but the concentrations of deoxycholic and oleic acid were significantly higher in the sucrose bolus group. In conclusion, the administration of sucrose as a bolus had a stronger effect than continuous sucrose feeding on some parameters related to colon carcinogenesis and might be considered a risk factor in colon carcinogenesis.

Characterisation of aberrant crypt foci in carcinogen-treated rats: association with intestinal carcinogenesis.

Carcinogen-treated rats develop foci of aberrant crypts in the colon (ACFs) that have been interpreted as preneoplastic lesions. To characterise ACFs further, we studied in the unsectioned colon of rats the number, multiplicity, some morphological characteristics and the type of mucin production in ACFs. In ACFs observed 115 days after the administration of 50 mg kg-1 1,2-dimethylhydrazine (DMH), crypt multiplicity [number of aberrant crypts (AC) per focus] was positively correlated (P < 0.0001) with the reduction of goblet cells, and with luminal and nuclear alterations in the cells surrounding the lumen of the ACs. We studied mucin production in the unsectioned colon, demonstrating that ACFs producing sulphomucins (like the normal distal rat colon) were progressively reduced when ACF multiplicity increased, whereas ACFs containing sialomucins (correlated with an increased risk of colon cancer) or both sulphomucins and sialomucins increased with crypt multiplicity. We also studied ACFs in the colon and the occurrence of intestinal tumours in rats treated with azoxymethane (AOM; 64 mg kg-1). A significant association was found (P = 0.04) between tumours and the presence of 'large' ACFs (AC/ACF > 14 crypts) and a borderline significant association (P = 0.057) between the presence of tumours and sialomucin-producing ACFs. We found no association between the number of ACFs, ACF multiplicity and the presence of tumours.