Containment of carbapenem-resistant Enterobacterales colonisations and infections: Results from an integrated infection control intervention in a large hospital trust of northern Italy.

PURPOSE: We describe the results of an infection control intervention, implemented in 4 tertiary hospitals in Romagna, Italy, aiming at containing the spread of carbapenem-resistant Enterobacterales (CRE). METHODS: The intervention consisted of rectal screening in patients at risk for CRE; pre-emptive contact precaution waiting for screening results; timely notification of CRE identification and concomitant computerized alert; contact precaution for confirmed CRE-positive patients. We performed an interrupted time series analysis to compare the incidence of CRE bacteraemia, of other CRE infections, and CRE-positive rectal swabs in the pre and postintervention period (January 2015-July 2017 and August 2017-June 2020, respectively). RESULTS: 4,332 CRE isolates were collected. Klebsiella pneumoniae was the most represented pathogen (n = 3,716, 85%); KPC production was the most common resistance mechanism (n = 3,896, 90%). The incidence rate of CRE bacteraemia significantly decreased from 0.554 to 0.447 episodes per 10.000 patient days in the early postintervention period (P = .001). The incidence rate of other CRE infections significantly decreased from 2.09 to 1.49 isolations per 10.000 patient days in the early postintervention period (P = .021). The monthly number of rectal swabs doubled in the postintervention period and there was a significant reduction trend of CRE-positive swabs, sustained over time (P < .001). CONCLUSIONS: The infection control intervention was successful in containing the spread of CRE infections and colonisations.

Cerebral low-density lipoprotein (LDL) uptake is stimulated by acute bile drainage.

Although the cholesterol pool in the central nervous system is considered to be relatively stable, few studies have tested this assumption. The aim of the study was to gain further information on the communication between the extracerebral organs and the brain as far as cholesterol and lipoprotein transport are concerned. Receptor-dependent as well as receptor-independent LDL uptake in the brain were measured, by established methods, after constant 1-h intravenous infusions of [14C]sucrose-labelled hamster LDL and methylated human LDL, both in hamsters with an acute bile fistula and in control animals with an intact enterohepatic circulation. The receptor-dependent LDL uptake in the brain promptly showed a significant increase after the construction of the bile fistula. However, there was no difference in the receptor-independent LDL uptake between the bile fistula and control animals. The studies indicate the presence of close communications between extracerebral and brain cholesterol. Changes in the extracerebral compartments of cholesterol are, apparently, readily sensed by the LDL receptor in the brain and promptly evoke appropriate modifications in its activity.

Body water distribution in severe obesity and its assessment from eight-polar bioelectrical impedance analysis.

OBJECTIVE: To measure body water distribution and to evaluate the accuracy of eight-polar bioelectrical impedance analysis (BIA) for the assessment of total body water (TBW) and extracellular water (ECW) in severe obesity. DESIGN: Cross-sectional study. SETTING: Obesity clinic. SUBJECTS: In all, 75 women aged 18-66 y, 25 with body mass index (BMI) between 19.1 and 29.9 kg/m(2) (ie not obese), 25 with BMI between 30.0 and 39.9 kg/m(2) (ie class I and II obese), and 25 with BMI between 40.0 and 48.2 kg/m(2) (ie class III obese). METHODS: TBW and ECW were measured by (2)H(2)O and Br dilution. Body resistance (R) was obtained by summing the resistances of arms, trunk and legs as measured by eight-polar BIA (InBody 3.0, Biospace, Seoul, Korea). The resistance index at a frequency of x kHz (RI(x)) was calculated as height (2)/R(x). RESULTS: ECW : TBW was similar in women with class III (46+/-3%, mean+/-s.d.) and class I-II obesity (45+/-3%) but higher than in nonobese women (39+/-3%, P<0.05). In a random subsample of 37 subjects, RI(500) explained 82% of TBW variance (P<0.0001) and cross-validation of the obtained algorithm in the remaining 38 subjects gave a percent root mean square error (RMSE%) of 5% and a pure error (PE) of 2.1 l. In the same subjects, RI(5) explained 87% of ECW variance (P<0.0001) and cross-validation of the obtained algorithm gave a RMSE% of 8% and a PE of 1.4 l. The contribution of weight and BMI to the prediction of TBW and ECW was nil or negligible on practical grounds. CONCLUSIONS: ECW : TBW is similar in women with class I-II and class III obesity up to BMI values of 48.2 kg/m(2). Eight-polar BIA offers accurate estimates of TBW and ECW in women with a wide range of BMI (19.1-48.2 kg/m(2)) without the need of population-specific formulae.

Accuracy of eight-polar bioelectrical impedance analysis for the assessment of total and appendicular body composition in peritoneal dialysis patients.

OBJECTIVE: To establish the accuracy of bioelectrical impedance analysis (BIA) for the assessment of total and appendicular body composition in peritoneal dialysis (PD) patients. DESIGN: Cross-sectional study. SETTING: University Nephrology Clinic. SUBJECTS: In all, 20 PD patients and 77 healthy controls matched for gender, age and body mass index. METHODS: Whole-body fat-free mass (FFM) and appendicular lean tissue mass (LTM) were measured by dual-energy X-ray absorptiometry. Resistance (R) of arms, trunk and legs was measured by eight-polar BIA at frequencies of 5, 50, 250 and 500 kHz. Whole-body resistance was calculated as the sum of R of arms, trunk and legs. The resistance index (RI) was calculated as the ratio between squared height and whole-body or segmental R. RESULTS: RI at 500 kHz was the best predictor of FFM, LTM(arm) and LTM(leg) in both PD patients and controls. Equations developed on controls overestimated FFM and LTM(arm) and underestimated LTM(leg) when applied to PD patients. Specific equations were thus developed for PD patients. Using these equations, the percent root mean-squared errors of the estimate for PD patients vs controls were 5 vs 6% for FFM, 8 vs 8% for LTM(arm) and 7 vs 8% for LTM(leg). CONCLUSION: Eight-polar BIA offers accurate estimates of total and appendicular body composition in PD patients, provided that population-specific equations are used.

Serum lipid and lipoprotein patterns in patients with liver cirrhosis and chronic active hepatitis.

BACKGROUND: An impaired lipid metabolism is often found in patients with chronic liver diseases. Unfortunately, few studies are available concerning serum lipid and lipoprotein levels in patients with liver cirrhosis and chronic active hepatitis (CAH). OBJECTIVES: To evaluate low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), and total cholesterol serum levels in patients with cirrhosis and CAH and control patients and to relate the findings to the severity of the cirrhosis (Child classification). METHODS: We measured the serum lipid pattern in 34 consecutive patients with liver cirrhosis (15 men and 19 women; mean [+/-SD] age, 55 +/- 14 years; Child classes: 14 in A, 9 in B, 11 in C; patients with biliary cirrhosis were excluded), 34 patients with CAH, and 34 control patients. The 3 groups were matched for sex and age. Total serum, HDL cholesterol, and triglyceride levels were measured by enzymatic methods; serum LDL and VLDL levels were calculated. RESULTS: In patients with cirrhosis, there was a significant decrease in LDL, HDL, and total cholesterol serum levels compared with both the patients with CAH and the control patients, while the VLDL cholesterol level in patients with cirrhosis was significantly lower compared with the control patients alone. A significant decrease in total cholesterol levels was also observed in the CAH group when compared with the control patients. In patients with cirrhosis, levels of LDL, HDL, and total serum cholesterol were progressively lower when comparing patients in Child class A with patients in class C. CONCLUSIONS: In this study, the striking decrease in the level of serum LDL cholesterol in patients with liver disease was related to the increasing severity of the disease. Accordingly, the assessment of the serum LDL cholesterol level is important for an effective treatment and prognostic evaluation of patients with chronic liver disease.

Effect of ursodeoxycholic acid on hepatic LDL binding and uptake in dietary hypercholesterolemic hamsters.

Administration of ursodeoxycholic acid (UDCA) has been shown to decrease serum total and low density lipoprotein (LDL) cholesterol in hypercholesterolemic patients with primary biliary cirrhosis. Results of previous studies prompted us to postulate that the cholesterol-lowering effect of UDCA may be due, at least in part, to a direct increment in hepatic LDL receptor binding [Bouscarel et al., Biochem J, 1991;280:589; Bouscarel et al., Lipids 1995;30:607]. The aim of the present investigation was to determine the ability of UDCA to enhance hepatocellular LDL receptor recruitment, as determined by its effect in vivo on LDL uptake, and its effect in vitro on LDL binding, under conditions of moderately elevated serum cholesterol. Study groups consisted of male golden Syrian hamsters fed either a standard chow diet (control), a 0.15% cholesterol-containing diet, or a 0.15% cholesterol-containing diet supplemented with either 0.1% UDCA, or 0.1% chenodeoxycholic acid (CDCA). Cholesterol feeding increased (P<0.01) total serum cholesterol by 44%, and was associated with a 10-fold accumulation of cholesteryl esters in the liver (P<0.01). In vivo, hepatic uptake of [U-(14)C]sucrose-labeled hamster LDL was increased (P<0.05) to a level of 454+/-101 microl in animals fed a cholesterol-containing diet supplemented with UDCA, compared to that either without UDCA (337+/-56 microl), or with CDCA (240+/-49 microl). The hepatic uptake of [U-(14)C]sucrose-labeled methylated human LDL, a marker of LDL receptor-independent LDL uptake, was unaffected by bile acid feeding. In vitro, specific binding of [125I]hamster LDL to isolated hepatocytes was determined at 4 degrees C, in presence and absence of 700 micromol/l UDCA. The K(D) ranged from 25 to 31 microg/ml, and was not affected by either cholesterol feeding or UDCA. In the presence of UDCA, the B(max) was increased by 19% (P<0.05) in cells isolated from control animals and by 29% (P<0.01) in cells isolated from hamsters fed a cholesterol-supplemented diet. In conclusion, in dietary hypercholesterolemic hamsters, both chronic in-vivo and acute in-vitro treatments with UDCA resulted in restoration of hepatic LDL binding and uptake to levels observed in control hamsters.

Effect of dietary oils containing different amounts of precursor and derivative fatty acids on prostaglandin E2 synthesis in liver, kidney and lung of rats.

The availability of the fatty acids which are precursors of prostaglandins is affected by dietary intake. We have studied, in particular, the effects of dietary intake of lipids with different amounts of precursor and derivative fatty acids on the synthesis of prostaglandin E2 (PGE2) in rat liver, kidney and lung. Fifteen-month-old rats were fed for 3 months diets containing different amounts of oleic, linoleic, alpha linolenic, gamma linolenic and stearidonic acids. The fatty acid compositions of total phospholipids and prostaglandin E2 levels of liver, kidney and lung were investigated. In the organs studied, the intake of lipids at different amount of precursor/derivative fatty acids caused variations in the fatty acid composition of phospholipids. PGE2 showed different values which did not seem directly affected by tissue availability of arachidonate but by the effect of dietary lipids on the metabolic pool of polyunsaturated fatty acids (PUFAs).

Effects of bile acid depletion and of ursodeoxycholic and chenodeoxycholic acids on biliary protein secretion in the hamster.

The effect of changes of both the rate of secretion and the composition of bile acids on biliary proteins was studied in a bile fistula hamster model. Biliary protein secretion as well as bile flow and bile acid secretion were studied in response to intravenous infusions of low, medium and high doses of ursodeoxycholic acid and chenodeoxycholic acid in comparison to the infusion of the normal saline carrier (control) solution. The control-infused animals showed a marked and statistically significant increase in both the concentration and total excretion of biliary proteins. All three doses of ursodeoxycholic acid either prevented the increase of protein concentration or led to its decrease. The low and medium doses of chenodeoxycholic acid had similar effects. However, the high dose of this bile acid was cholestatic and increased the biliary protein concentration. The results of the study indicate that decreases in bile acid secretion, as they occur after an interruption of the enterohepatic circulation, may lead to major increases in biliary protein concentration. The study also shows that these changes in protein secretion, which may promote nucleation, are reversed by the cholelitholytic bile acids, ursodeoxycholic acid and chenodeoxycholic acid.

Accuracy of an eight-point tactile-electrode impedance method in the assessment of total body water.

OBJECTIVE: To establish the accuracy of an eight-polar tactile-electrode impedance method in the assessment of total body water (TBW). DESIGN: Transversal study. SETTING: University department. SUBJECTS: Fifty healthy subjects (25 men and 25 women) with a mean (s.d.) age of 40 (12) y. METHODS: TBW measured by deuterium oxide dilution; resistance (R) of arms, trunk and legs measured at frequencies of 5, 50, 250 and 500 kHz with an eight-polar tactile-electrode impedance-meter (InBody 3.0, Biospace, Seoul, Korea). RESULTS: An algorithm for the prediction of TBW from the whole-body resistance index at 500 kHz (height (2)/R(500) where R is the sum of the segmental resistances of arms, trunk and legs) was developed in a randomly chosen subsample of 35 subjects. This algorithm had an adjusted coefficient of determination (r2(adj)) of 0.81 (P<0.0001) and a root mean square error (RMSE) of 3.6 l (9%). Cross-validation of the predictive algorithm in the remaining 15 subjects gave an r2(adj) of 0.87 (P<0.0001) and an RMSE of 3.0 l (8%). The precision of eight-polar BIA, determined by measuring R three times a day for five consecutive days in a fasting subject, was < or =2.8% for all segments and frequencies. CONCLUSION: Eight-polar BIA is a precise method that offers accurate estimates of TBW in healthy subjects. This promising method should undergo further studies of precision and its accuracy in assessing extracellular water and appendicular body composition should be determined. SPONSORSHIP: Modena and Reggio Emilia University.

Comparison of bioelectrical impedance analysis and dual-energy X-ray absorptiometry for the assessment of appendicular body composition in anorexic women.

OBJECTIVE: To establish the accuracy of bioelectrical impedance analysis (BIA) for the assessment of appendicular body composition in anorexic women. DESIGN: Cross-sectional study. SETTING: Outpatient University Clinic. SUBJECTS: A total of 39 anorexic and 25 control women with a mean (s.d.) age of 21 (3) y. METHODS: Total, arm and leg fat-free mass (FFM) were measured by dual-energy X-ray absorptiometry and predicted from total and segmental BIA at 50 kHz. The predictor variable was the resistance index (Rl), that is, the ratio of height (2) to body resistance for the whole body and the ratio of length(2)/limb resistance for the arm and leg. RESULTS: Predictive equations developed on controls overestimated total, arm and leg FFM in anorexics (P<0.0001). Population-specific equations gave a satisfactory estimate of total and appendicular FFM in anorexics (P=NS) but had higher percent root mean square errors (RMSEs%) as compared to those developed on controls (8% vs 5% for whole body, 12% vs 10% for arm and 10% vs 8% for leg). The accuracy of the estimate of total and leg FFM in anorexics was improved by adding body weight (Wt) as a predictor with Rl (RMSE%=5% vs 8% and 7% vs 10%, respectively). However, the same accuracy was obtained using Wt alone, suggesting that in anorexics, BIA at 50 kHz is not superior to Wt for assessing total and leg FFM. CONCLUSION: BIA shows some potential for the assessment of appendicular body composition in anorexic women. However, Wt is preferable to BIA at 50 kHz on practical grounds. Further studies should consider whether frequencies >50 kHz give better estimates of appendicular composition in anorexics as compared to Wt. SPONSORSHIP: University of Napoli.

Some applications of indirect calorimetry to sports medicine.

Some applications of indirect calorimetry to sports medicine are discussed and exemplified by case reports. In particular, it is suggested that oxigen consumption can be employed to assess the effects of physical activity on fat-free tissues and that the respiratory quotient may offer some insights into the food habits of athletes.

Interaction of potentially toxic bile acids with human plasma proteins: binding of lithocholic (3 alpha-hydroxy-5 beta-cholan-24-oic) acid to lipoproteins and albumin.

The binding of lithocholic acid to different plasma fractions was studied. When whole plasma was incubated for 8 hr, approximately 25% of the incubated [14C]lithocholic acid was bound to the lipoprotein and lipoprotein-free, albumin-rich fractions. An average of 87.6% of the bound-lithocholic acid was present in the lipoprotein-free, albumin-rich fraction, 7.2% in high density lipoproteins, 2.2% in low density lipoproteins, 1.0% in intermediate density lipoproteins and 2.0% in very low density lipoproteins. Expressed as binding per microgram protein, considerably less [14C]lithocholic acid was bound to the lipoprotein-free, albumin-rich fraction, than to the lipoproteins. The binding of [14C]lithocholic acid after the incubation of the isolated plasma fractions was similar to that found after the incubation of whole plasma. The highest transfer of [14C]lithocholic acid occurred from the lipoprotein-free, albumin-rich fraction to the lipoprotein fractions. The studies indicate, that, although the largest amount of lithocholic acid is bound to the lipoprotein-free, albumin-rich fraction, per microgram protein, the binding of lithocholic acid to lipoproteins is more pronounced and stable than that bound to the lipoprotein-free, albumin-rich fraction. Since lipoproteins, in contrast to albumin, are internalized by most tissues, they may be important carriers into cells of lithocholic acid and other potentially toxic or tumorigenic bile acids.

Treatment of constipation with chenodeoxycholic acid.

The aim of this study was to investigate whether the cathartic effect of chenodeoxycholic acid (CDCA) could be helpful in the management of chronic constipation. Twenty cholesterol gall-stone patients with chronic constipation were randomly treated with either CDCA (750 mg/day in three divided doses at meals) or placebo for a period of 4 weeks. The administration of CDCA produced a significant increase of stool frequency and a decrease of stool consistency, while placebo was not effective in improving the bowel habit of the patients. As some patients complained of diarrhoea, and some had no modification of bowel frequency, further studies are needed to determine the most appropriate dose for each patient.

Gestational weight gain in overweight and obese women enrolled in a healthy lifestyle and eating habits program.

OBJECTIVES: To determine whether changes in lifestyle in women with BMI > 25 could decrease gestational weight gain and unfavorable pregnancy outcomes. METHODS: Women with BMI > 25 were randomized at 1st trimester to no intervention or a Therapeutic Lifestyle Changes (TLC) Program including diet (overweight: 1700 kcal/day, obese: 1800 kcal/day) and mild physical activity (30 min/day, 3 times/week). At baseline and at the 36th week women filled-in a Food Frequency Questionnaire. OUTCOMES: gestational weight gain, gestational diabetes mellitus, gestational hypertension, preterm delivery. Data stratified by BMI categories. RESULTS: Socio-demographic features were similar between groups (TLC: 33 cases, CONTROLS: 28 cases). At term, gestational weight gain in obese women randomized to TLC group was lower (6.7 ± 4.3 kg) versus controls (10.1 ± 5.6 kg, p = 0.047). Gestational diabetes mellitus, gestational hypertension and preterm delivery were also significantly lower. TLC was an independent factor in preventing gestational weight gain, gestational diabetes mellitus, gestational hypertension. Significant changes in eating habits occurred in the TLC group, which increased the number of snacks, the intake of fruits-vegetables and decreased the consumption of sugar. CONCLUSIONS: A caloric restriction associated to changes in eating behavior and constant physical activity, is able to reduce gestational weight gain and related pregnancy complications in obese women.

Growth: healthy status and active food model in pediatrics.

OBJECTIVE: The brain integrates peripheral signals of nutrition in order to maintain a stable body weight. Nutritional status defined as the results of introduction, absorption, and utilization of the nutrients could be interpreted with the base of the relationship between nutritional status and healthy status. In this view, energy balance, body function, and body composition are three entities correlated to each other to the healthy status. AIM: To discuss the nutritional status in relation with healthy status, and its relationship with growth and nutrients. METHODS: A review of the available literature on food patterns and active food model was carried out. RESULTS: In the reviewed studies, strategies that could offer promising results to prevent overweight and obesity were discussed, in particular in the light of functional foods that effect energy metabolism and fat partitioning. CONCLUSION: At this moment it is necessary to proactively discuss and promote healthy eating behaviors among children at an early age and empower parents to promote children's ability to self-regulate energy intake while providing appropriate structure and boundaries around eating.

Bile acid dissolution therapy of gallbladder stones.

Oral cholelitholytic bile acid therapy has become established treatment for selected patients with cholesterol gallstones. The treatment finds its clinical application both alone and in combination with ESWL. UDCA alone or, less commonly, a combination of this bile acid with CDCA is used. Optimal results can be expected only in carefully selected patients. Bile acid dissolution therapy is most successful in patients with radiolucent gallstones which are < or = 0.5 cm in diameter or are shown by OCG to be floating. Dissolution is seldom seen when the stones are > 1 cm in size. Cholelitholytic treatment in combination with ESWL yields optimal results in single radiolucent gallstones which are not greater than 2 cm. ESWL thus makes it possible to use medical treatment effectively in single 1-2 cm gallstones when bile acids alone would not be successful. Bile acid treatment is extremely safe, especially if UDCA is given without the addition of CDCA.

Bile acid-induced diarrhoea.

Three types of bile acid-induced diarrhoea can be distinguished. The best documented and most common entity is represented by type I bile acid malabsorption, which occurs as the result of a pathologically, anatomically defined ileopathy. Type II bile acid malabsorption is found in the setting of a morphologically completely normal ileum. This primary disorder of bile acid transport, which has been described in only a few paediatric and adult patients, appears to be rare. The third variety of bile acid malabsorption is characterized by the history of a previous cholecystectomy and/or by the presence of other gastroenterological conditions. Severe bile acid malabsorption is relatively uncommon in the type III syndrome. Even in the presence of severe bile acid malabsorption, patients with this condition are rarely found to have secretory concentrations of faecal bile acids, and/or rarely respond satisfactorily to cholestyramine. Present data suggest that bile acids play no significant role in the pathogenesis of idiopathic diarrhoea. A careful history, the measurement of stool weight and pH, a therapeutic trial of cholestyramine and the performance of a bile acid test, such as a bile acid breath test, can be used to establish the diagnosis of bile acid diarrhoea. Cholestyramine is the treatment of choice and is virtually always effective in this syndrome.

Modulation of bile secretion by hepatic low-density lipoprotein uptake and by chenodeoxycholic acid and ursodeoxycholic acid treatment in the hamster.

The effects of both apolipoprotein B,E receptor-dependent and receptor-independent uptake of low-density lipoprotein (LDL) in the liver on bile secretion were studied in bile fistula hamsters. Three groups of animals were studied after 4 wk of feeding either a control, chenodeoxycholic acid-, or ursodeoxycholic acid-containing diet. The hepatic receptor-dependent and receptor-independent uptake of LDL was related to both bile flow and biliary lipid secretion. The correlation with bile flow and biliary lipid secretion was positive for the receptor-dependent, but negative for the receptor-independent uptake of LDL. Although the receptor-mediated LDL uptake appeared to exert a strong influence on bile acid-independent bile flow, the receptor-independent uptake showed a significant relation with biliary bile acid excretion. Differences between the two mechanisms of LDL uptake were also evident in the biliary bile acid-cholesterol coupling, which was significantly stronger during receptor-independent than during receptor-dependent uptake of LDL. The effects of LDL uptake on bile secretion were modulated by the experimentally induced changes in both the content and composition of bile acids in the enterohepatic circulation.

Isolation and identification of delta 6-lithocholenic acid (3 alpha-hydroxy-5 beta-6-cholen-24-oic acid) as an intestinal bacterial metabolite of chenodeoxycholic acid in man.

Fecal bacterial biotransformation studies of chenodeoxycholic acid were performed. Incubations were carried out for 30-s to 12-h time intervals. delta 6-Lithocholenic acid was isolated by thin-layer chromatography. Its structure was confirmed by gas-liquid chromatography and mass spectrometry. The proportion of chenodeoxycholic acid biotransformed to delta 6-lithocholenic acid consistently ranged from 5.5 to 14.0%.