http://www.ncbi.nlm.nih.gov/pubmed/22327200
Curr Opin Anaesthesiol. 2012 Feb 9. [Epub ahead of print]
Cardiopulmonary exercise testing: does it improve perioperative care and outcome?
Stringer W, Casaburi R, Older P.
Source
aDepartment of Medicine, Geffen School of Medicine at UCLA, Harbor-UCLA Medical Center, Torrance, California, USA bDepartment of Anesthesia, Swinburne University of Technology cDepartment of Anesthesia, University of Melbourne Medical School, Melbourne, Australia.
Abstract
PURPOSE OF REVIEW:
We reviewed recent articles, guidelines, and meta-analyses concerning the use of cardiopulmonary exercise testing (CPET) in preoperative risk evaluation and fitness for surgery. When the risk of surgery mortality is high (e.g. >5%), and/or the preoperative state of the patient indicates increased propensity toward morbidity and mortality (advanced age, presence of cardiovascular risk factors, multisystem disease, poor functional status, and so on), the thoroughness of the perioperative assessment should be intensified beyond the standard history and physical, basic laboratories, and electrocardiogram stress testing to include CPET.
RECENT FINDINGS:
The CPET variables of peak oxygen uptake, anaerobic threshold, oxygen pulse, and ventilatory efficiency appropriately focus upon the cardiopulmonary reserve required to respond to metabolic stress and, therefore, are ideal to predict operative surgery outcomes. The focus should not be on using CPET to deny surgery to patients, but rather to define the level of postoperative care required to minimize risk.
SUMMARY:
Using a small number of important variables obtained from CPET an accurate picture of the patient's future response to perioperative stress can be obtained. Consideration should be given to performing a CPET in any preoperative patient who has increased risk or is scheduled to undergo a high risk surgical intervention. This strategy assists the anesthetist, surgeon, patients, and their families in appropriate perioperative planning.
Friday, February 17, 2012
Fitness and performance genomics: 2011
http://www.ncbi.nlm.nih.gov/pubmed/22330029
Med Sci Sports Exerc. 2012 Feb 9. [Epub ahead of print]
Advances in Exercise, Fitness, and Performance Genomics in 2011.
Roth SM, Rankinen T, Hagberg JM, Loos RJ, Perusse L, Sarzynski MA, Wolfarth B, Bouchard C.
Source
1Department of Kinesiology, School of Public Health, University of Maryland, College Park, MD 2Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 3Medical Research Council Epidemiological Unit, Institute of Metabolic Science, Cambridge, United Kingdom 4Charles R. Bronfman, Institute of Personalized Medicine, Mount Sinai School of Medicine, New York, NY 5Department of Kinesiology, Laval University, Ste-Foy, Québec, Canada 6Preventive and Rehabilitative Sports Medicine, Technical University Munich, Munich, Germany.
ABSTRACT: This review of the exercise genomics literature emphasizes the highest quality papers published in 2011. Given this emphasis on the best publications, only a small number of published papers are reviewed. One study found that physical activity levels were significantly lower in patients with mitochondrial DNA mutations compared to controls. A two-stage fine mapping follow-up of a previous linkage peak found strong associations between sequence variation in the activin A receptor, type-1B (ACVR1B) gene and knee extensor strength, with rs2854464 emerging as the most promising candidate polymorphism. The association of higher muscular strength with the rs2854464 A-allele was confirmed in two separate cohorts. A study using a combination of transcriptomic and genomic data identified a comprehensive map of the transcriptomic features important for aerobic exercise training-induced improvements in maximal oxygen consumption, but no genetic variants derived from candidate transcripts were associated with trainability. A large-scale de novo meta-analysis confirmed that the effect of sequence variation in the fat mass and obesity-associated (FTO) gene on the risk of obesity differs between sedentary and physically active adults. Evidence for gene-physical activity interactions on type 2 diabetes risk was found in two separate studies. A large study of women found that physical activity modified the effect of polymorphisms in the lipoprotein lipase (LPL), hepatic lipase (LIPC), and cholesteryl ester transfer protein (CETP) genes, identified in previous genome-wide association study (GWAS) reports, on HDL-C. We conclude that a strong exercise genomics corpus of evidence would not only translate into powerful genomic predictors but would also have a major impact on exercise biology and exercise behavior research.
Med Sci Sports Exerc. 2012 Feb 9. [Epub ahead of print]
Advances in Exercise, Fitness, and Performance Genomics in 2011.
Roth SM, Rankinen T, Hagberg JM, Loos RJ, Perusse L, Sarzynski MA, Wolfarth B, Bouchard C.
Source
1Department of Kinesiology, School of Public Health, University of Maryland, College Park, MD 2Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 3Medical Research Council Epidemiological Unit, Institute of Metabolic Science, Cambridge, United Kingdom 4Charles R. Bronfman, Institute of Personalized Medicine, Mount Sinai School of Medicine, New York, NY 5Department of Kinesiology, Laval University, Ste-Foy, Québec, Canada 6Preventive and Rehabilitative Sports Medicine, Technical University Munich, Munich, Germany.
ABSTRACT: This review of the exercise genomics literature emphasizes the highest quality papers published in 2011. Given this emphasis on the best publications, only a small number of published papers are reviewed. One study found that physical activity levels were significantly lower in patients with mitochondrial DNA mutations compared to controls. A two-stage fine mapping follow-up of a previous linkage peak found strong associations between sequence variation in the activin A receptor, type-1B (ACVR1B) gene and knee extensor strength, with rs2854464 emerging as the most promising candidate polymorphism. The association of higher muscular strength with the rs2854464 A-allele was confirmed in two separate cohorts. A study using a combination of transcriptomic and genomic data identified a comprehensive map of the transcriptomic features important for aerobic exercise training-induced improvements in maximal oxygen consumption, but no genetic variants derived from candidate transcripts were associated with trainability. A large-scale de novo meta-analysis confirmed that the effect of sequence variation in the fat mass and obesity-associated (FTO) gene on the risk of obesity differs between sedentary and physically active adults. Evidence for gene-physical activity interactions on type 2 diabetes risk was found in two separate studies. A large study of women found that physical activity modified the effect of polymorphisms in the lipoprotein lipase (LPL), hepatic lipase (LIPC), and cholesteryl ester transfer protein (CETP) genes, identified in previous genome-wide association study (GWAS) reports, on HDL-C. We conclude that a strong exercise genomics corpus of evidence would not only translate into powerful genomic predictors but would also have a major impact on exercise biology and exercise behavior research.
Does eating right make up for "obesigenic" lifestyle of Quebec children?
http://www.ncbi.nlm.nih.gov/pubmed/22332048
Adv Nutr. 2011 Mar;2(2):167S-70S. Epub 2011 Mar 10.
Healthy eating at school to compensate for the activity-related obesigenic lifestyle in children and adolescents: the quebec experience.
Tremblay A, Arguin H.
Source
Division of Kinesiology, Laval University, Quebec City, Canada, G1V 0A6.
Abstract
In this article, we describe the Quebec experience about the determinants of childhood obesity and the search for solutions, which are well adapted to the constraints of the current lifestyle. As expected, it is likely that a decrease in physical fitness and its related sedentariness as well as suboptimal food habits have contributed to the increase in overweight prevalence that was observed between 1980 and 2000. Our research experience suggests that other less suspected activity related factors have also played an important role in the occurrence of the obesity epidemic. This is particularly the case for short sleeping and demanding mental work, which are features of our modern lifestyle. Because there is no foreseeable prospect for a change in sleep and mental work habits, we argue that compensations in other factors may be necessary to prevent weight gain in this new context. We thus developed a concept of food design aiming at the maximization of the satiating properties of a food or a meal course. In this context, we were successful in the design of healthy lunch bags for students of a school located in a low socioeconomic area. Indeed, for a majority of menus, an optimal compromise seemed to be reached between nutrient composition, satiating potential, palatability, and financial accessibility. In summary, the Quebec experience reveals that childhood obesity is a complex problem that partly results from unsuspected environmental factors that deserve creative solutions to at least partly compensate for their effect.
Adv Nutr. 2011 Mar;2(2):167S-70S. Epub 2011 Mar 10.
Healthy eating at school to compensate for the activity-related obesigenic lifestyle in children and adolescents: the quebec experience.
Tremblay A, Arguin H.
Source
Division of Kinesiology, Laval University, Quebec City, Canada, G1V 0A6.
Abstract
In this article, we describe the Quebec experience about the determinants of childhood obesity and the search for solutions, which are well adapted to the constraints of the current lifestyle. As expected, it is likely that a decrease in physical fitness and its related sedentariness as well as suboptimal food habits have contributed to the increase in overweight prevalence that was observed between 1980 and 2000. Our research experience suggests that other less suspected activity related factors have also played an important role in the occurrence of the obesity epidemic. This is particularly the case for short sleeping and demanding mental work, which are features of our modern lifestyle. Because there is no foreseeable prospect for a change in sleep and mental work habits, we argue that compensations in other factors may be necessary to prevent weight gain in this new context. We thus developed a concept of food design aiming at the maximization of the satiating properties of a food or a meal course. In this context, we were successful in the design of healthy lunch bags for students of a school located in a low socioeconomic area. Indeed, for a majority of menus, an optimal compromise seemed to be reached between nutrient composition, satiating potential, palatability, and financial accessibility. In summary, the Quebec experience reveals that childhood obesity is a complex problem that partly results from unsuspected environmental factors that deserve creative solutions to at least partly compensate for their effect.
From San Diego State U: Latino children and physical activity during recess
http://www.ncbi.nlm.nih.gov/pubmed/22332049
Adv Nutr. 2011 Mar;2(2):171S-6S. Epub 2011 Mar 10.
Effects of a Multi-Pronged Intervention on Children's Activity Levels at Recess: The Aventuras para Niños Study.
Elder JP, McKenzie TL, Arredondo EM, Crespo NC, Ayala GX.
Source
Graduate School of Public Health, and Institute for Behavioral and Community Health, San Diego State University Research Foundation, San Diego, CA 9245.
Abstract
Latino children spend more time in sedentary activities than other American children, and only ~1 in 5 Latino children in public elementary and middle schools meet all 6 fitness standards in statewide fitness testing. Schools that facilitate physical activity (PA) by maintaining playgrounds and providing physical education classes have children who are more active and less overweight. The aims of the present study were to examine the extent to which several social and physical environmental changes in school settings resulted in observed changes in area characteristics and children's activity levels during recess. Thirteen elementary schools serving predominately Mexican American children were randomized into control or activity and nutrition environmental intervention conditions. Playgrounds and activities were restructured in 6 intervention schools to promote more PA. After 1 y, there were no overall statistical differences between treatment groups in PA or sedentary behavior in these settings and results did not differ by gender. Changing the social and physical environments to promote children's moderate-to-vigorous PA is important to the design of active and healthy recess environments. The present results are not conclusive as to the link between these interventions and actual behavior, but show sufficient promise for further population and setting specific research.
Adv Nutr. 2011 Mar;2(2):171S-6S. Epub 2011 Mar 10.
Effects of a Multi-Pronged Intervention on Children's Activity Levels at Recess: The Aventuras para Niños Study.
Elder JP, McKenzie TL, Arredondo EM, Crespo NC, Ayala GX.
Source
Graduate School of Public Health, and Institute for Behavioral and Community Health, San Diego State University Research Foundation, San Diego, CA 9245.
Abstract
Latino children spend more time in sedentary activities than other American children, and only ~1 in 5 Latino children in public elementary and middle schools meet all 6 fitness standards in statewide fitness testing. Schools that facilitate physical activity (PA) by maintaining playgrounds and providing physical education classes have children who are more active and less overweight. The aims of the present study were to examine the extent to which several social and physical environmental changes in school settings resulted in observed changes in area characteristics and children's activity levels during recess. Thirteen elementary schools serving predominately Mexican American children were randomized into control or activity and nutrition environmental intervention conditions. Playgrounds and activities were restructured in 6 intervention schools to promote more PA. After 1 y, there were no overall statistical differences between treatment groups in PA or sedentary behavior in these settings and results did not differ by gender. Changing the social and physical environments to promote children's moderate-to-vigorous PA is important to the design of active and healthy recess environments. The present results are not conclusive as to the link between these interventions and actual behavior, but show sufficient promise for further population and setting specific research.
Childhood fitness in the Czech Republic
http://www.ncbi.nlm.nih.gov/pubmed/22332050
Adv Nutr. 2011 Mar;2(2):177S-81S. Epub 2011 Mar 10.
From an inactive and obese to a fit child: how long is the way? Czech experiences.
Pařízková J.
Source
Obesity Management Centre, Institute of Endocrinology, Prague 1, 116 94 Czech Republic.
Abstract
To achieve a higher level of overall fitness and to prevent obesity with accompanying comorbidities requires life-long effort starting early in life during the prenatal period. A sufficiently intense, regular, and ongoing physical activity regime and adequate exercise are indispensable, along with monitored diet. Once acquired, a desirable level of body composition and functional capacity can be lost relatively quickly due to regime interruption. Adhering to the optimal regime of diet and activity that not long ago used to be the norm is especially difficult under present life conditions, and new and innovative procedures have to be defined and introduced.
Adv Nutr. 2011 Mar;2(2):177S-81S. Epub 2011 Mar 10.
From an inactive and obese to a fit child: how long is the way? Czech experiences.
Pařízková J.
Source
Obesity Management Centre, Institute of Endocrinology, Prague 1, 116 94 Czech Republic.
Abstract
To achieve a higher level of overall fitness and to prevent obesity with accompanying comorbidities requires life-long effort starting early in life during the prenatal period. A sufficiently intense, regular, and ongoing physical activity regime and adequate exercise are indispensable, along with monitored diet. Once acquired, a desirable level of body composition and functional capacity can be lost relatively quickly due to regime interruption. Adhering to the optimal regime of diet and activity that not long ago used to be the norm is especially difficult under present life conditions, and new and innovative procedures have to be defined and introduced.
Thursday, February 16, 2012
From U Florida: Pharmacokinetics of fructose
http://www.ncbi.nlm.nih.gov/pubmed/22152650
Metabolism. 2011 Dec 5. [Epub ahead of print]
Effects of high-fructose corn syrup and sucrose on the pharmacokinetics of fructose and acute metabolic and hemodynamic responses in healthy subjects.
Le MT, Frye RF, Rivard CJ, Cheng J, McFann KK, Segal MS, Johnson RJ, Johnson JA.
Source
Department of Pharmacotherapy and Translational Research, University of Florida, Gainesville, FL 32610, USA.
Abstract
It is unclear whether high-fructose corn syrup (HFCS), which contains a higher amount of fructose and provides an immediate source of free fructose, induces greater systemic concentrations of fructose as compared with sucrose. It is also unclear whether exposure to higher levels of fructose leads to increased fructose-induced adverse effects. The objective was to prospectively compare the effects of HFCS- vs sucrose-sweetened soft drinks on acute metabolic and hemodynamic effects. Forty men and women consumed 24 oz of HFCS- or sucrose-sweetened beverages in a randomized crossover design study. Blood and urine samples were collected over 6 hours. Blood pressure, heart rate, fructose, and a variety of other metabolic biomarkers were measured. Fructose area under the curve and maximum concentration, dose-normalized glucose area under the curve and maximum concentration, relative bioavailability of glucose, changes in postprandial concentrations of serum uric acid, and systolic blood pressure maximum levels were higher when HFCS-sweetened beverages were consumed as compared with sucrose-sweetened beverages. Compared with sucrose, HFCS leads to greater fructose systemic exposure and significantly different acute metabolic effects.
Metabolism. 2011 Dec 5. [Epub ahead of print]
Effects of high-fructose corn syrup and sucrose on the pharmacokinetics of fructose and acute metabolic and hemodynamic responses in healthy subjects.
Le MT, Frye RF, Rivard CJ, Cheng J, McFann KK, Segal MS, Johnson RJ, Johnson JA.
Source
Department of Pharmacotherapy and Translational Research, University of Florida, Gainesville, FL 32610, USA.
Abstract
It is unclear whether high-fructose corn syrup (HFCS), which contains a higher amount of fructose and provides an immediate source of free fructose, induces greater systemic concentrations of fructose as compared with sucrose. It is also unclear whether exposure to higher levels of fructose leads to increased fructose-induced adverse effects. The objective was to prospectively compare the effects of HFCS- vs sucrose-sweetened soft drinks on acute metabolic and hemodynamic effects. Forty men and women consumed 24 oz of HFCS- or sucrose-sweetened beverages in a randomized crossover design study. Blood and urine samples were collected over 6 hours. Blood pressure, heart rate, fructose, and a variety of other metabolic biomarkers were measured. Fructose area under the curve and maximum concentration, dose-normalized glucose area under the curve and maximum concentration, relative bioavailability of glucose, changes in postprandial concentrations of serum uric acid, and systolic blood pressure maximum levels were higher when HFCS-sweetened beverages were consumed as compared with sucrose-sweetened beverages. Compared with sucrose, HFCS leads to greater fructose systemic exposure and significantly different acute metabolic effects.
Fructose diet in mice induces cardiomyocyte disturbance
http://www.ncbi.nlm.nih.gov/pubmed/22198170
Am J Physiol Heart Circ Physiol. 2012 Feb;302(4):H964-72. Epub 2011 Dec 23.
Fructose diet treatment in mice induces fundamental disturbance of cardiomyocyte Ca2+ handling and myofilament responsiveness.
Mellor KM, Wendt IR, Ritchie RH, Delbridge LM.
Abstract
High fructose intake has been linked to insulin resistance and cardiac pathology. Dietary fructose-induced myocardial signaling and morphological alterations have been described, but whether cardiomyocyte function is influenced by chronic high fructose intake is yet to be elucidated. The goal of this study was to evaluate the cardiomyocyte excitation-contraction coupling effects of high dietary fructose and determine the capacity for murine cardiomyocyte fructose transport. Male C57Bl/6J mice were fed a high fructose diet for 12 wk. Fructose- and control-fed mouse cardiomyocytes were isolated and loaded with the fura 2 Ca(2+) fluorescent dye for analysis of twitch and Ca(2+) transient characteristics (4 Hz stimulation, 37°C, 2 mM Ca(2+)). Myocardial Ca(2+)-handling protein expression was determined by Western blot. Gene expression of the fructose-specific transporter, GLUT5, in adult mouse cardiomyocytes was detected by real-time and conventional RT-PCR techniques. Diastolic Ca(2+) and Ca(2+) transient amplitude were decreased in isolated cardiomyocytes from fructose-fed mice relative to control (16 and 42%, respectively), coincident with an increase in the time constant of Ca(2+) transient decay (24%). Dietary fructose increased the myofilament response to Ca(2+) (as evidenced by a left shift in the shortening-Ca(2+) phase loop). Protein expression of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a), phosphorylated (P) phospholamban (Ser(16)), and P-phospholamban (Thr(17)) was reduced, and protein phosphatase 2A expression increased, in fructose-fed mouse hearts. Hypertension and cardiac hypertrophy were not evident. These findings demonstrate that fructose diet-associated myocardial insulin resistance induces profound disturbance of cardiomyocyte Ca(2+) handling and responsiveness in the absence of altered systemic loading conditions.
PMID: 22198170 [PubMed - in process]
Am J Physiol Heart Circ Physiol. 2012 Feb;302(4):H964-72. Epub 2011 Dec 23.
Fructose diet treatment in mice induces fundamental disturbance of cardiomyocyte Ca2+ handling and myofilament responsiveness.
Mellor KM, Wendt IR, Ritchie RH, Delbridge LM.
Abstract
High fructose intake has been linked to insulin resistance and cardiac pathology. Dietary fructose-induced myocardial signaling and morphological alterations have been described, but whether cardiomyocyte function is influenced by chronic high fructose intake is yet to be elucidated. The goal of this study was to evaluate the cardiomyocyte excitation-contraction coupling effects of high dietary fructose and determine the capacity for murine cardiomyocyte fructose transport. Male C57Bl/6J mice were fed a high fructose diet for 12 wk. Fructose- and control-fed mouse cardiomyocytes were isolated and loaded with the fura 2 Ca(2+) fluorescent dye for analysis of twitch and Ca(2+) transient characteristics (4 Hz stimulation, 37°C, 2 mM Ca(2+)). Myocardial Ca(2+)-handling protein expression was determined by Western blot. Gene expression of the fructose-specific transporter, GLUT5, in adult mouse cardiomyocytes was detected by real-time and conventional RT-PCR techniques. Diastolic Ca(2+) and Ca(2+) transient amplitude were decreased in isolated cardiomyocytes from fructose-fed mice relative to control (16 and 42%, respectively), coincident with an increase in the time constant of Ca(2+) transient decay (24%). Dietary fructose increased the myofilament response to Ca(2+) (as evidenced by a left shift in the shortening-Ca(2+) phase loop). Protein expression of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a), phosphorylated (P) phospholamban (Ser(16)), and P-phospholamban (Thr(17)) was reduced, and protein phosphatase 2A expression increased, in fructose-fed mouse hearts. Hypertension and cardiac hypertrophy were not evident. These findings demonstrate that fructose diet-associated myocardial insulin resistance induces profound disturbance of cardiomyocyte Ca(2+) handling and responsiveness in the absence of altered systemic loading conditions.
PMID: 22198170 [PubMed - in process]
From Harvard: Sweeteners, obesity, and diabetes
http://www.ncbi.nlm.nih.gov/pubmed/22289979
Curr Diab Rep. 2012 Jan 31. [Epub ahead of print]
Sweeteners and Risk of Obesity and Type 2 Diabetes: The Role of Sugar-Sweetened Beverages.
Malik VS, Hu FB.
Source
Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA.
Abstract
Temporal patterns over the past three to four decades have shown a close parallel between the rise in added sugar intake and the global obesity and type 2 diabetes (T2D) epidemics. Sugar-sweetened beverages (SSBs), which include the full spectrum of soft drinks, fruit drinks, energy and vitamin water drinks, are composed of naturally derived caloric sweeteners such as sucrose, high fructose corn syrup, or fruit juice concentrates. Collectively they are the largest contributor to added sugar intake in the US diet. Over the past 10 years a number of large observational studies have found positive associations between SSB consumption and long-term weight gain and development of T2D and related metabolic conditions. Experimental studies provide insight into potential biological mechanisms and illustrate that intake of SSBs increases T2D and cardiovascular risk factors. SSBs promote weight gain by incomplete compensation of liquid calories and contribute to increased risk of T2D not only through weight gain, but also independently through glycemic effects of consuming large amounts of rapidly absorbable sugars and metabolic effects of fructose.
Curr Diab Rep. 2012 Jan 31. [Epub ahead of print]
Sweeteners and Risk of Obesity and Type 2 Diabetes: The Role of Sugar-Sweetened Beverages.
Malik VS, Hu FB.
Source
Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA.
Abstract
Temporal patterns over the past three to four decades have shown a close parallel between the rise in added sugar intake and the global obesity and type 2 diabetes (T2D) epidemics. Sugar-sweetened beverages (SSBs), which include the full spectrum of soft drinks, fruit drinks, energy and vitamin water drinks, are composed of naturally derived caloric sweeteners such as sucrose, high fructose corn syrup, or fruit juice concentrates. Collectively they are the largest contributor to added sugar intake in the US diet. Over the past 10 years a number of large observational studies have found positive associations between SSB consumption and long-term weight gain and development of T2D and related metabolic conditions. Experimental studies provide insight into potential biological mechanisms and illustrate that intake of SSBs increases T2D and cardiovascular risk factors. SSBs promote weight gain by incomplete compensation of liquid calories and contribute to increased risk of T2D not only through weight gain, but also independently through glycemic effects of consuming large amounts of rapidly absorbable sugars and metabolic effects of fructose.
Metabolic Syndrome: Caused by a high fructose, low fat/cholesterol diet?
http://www.ncbi.nlm.nih.gov/pubmed/22291727
Arch Med Sci. 2011 Feb;7(1):8-20. Epub 2011 Mar 8.
Is the metabolic syndrome caused by a high fructose, and relatively low fat, low cholesterol diet?
Seneff S, Wainwright G, Mascitelli L.
Source
Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA, USA.
Abstract
The metabolic syndrome (MetS) is manifested by a lipid triad which includes elevated serum triglycerides, small LDL particles, and low high-density lipoprotein (HDL) cholesterol, by central obesity (central adiposity), insulin resistance, glucose intolerance and elevated blood pressure, and it is associated with an increased risk of type 2 diabetes and coronary heart disease. We have developed a new hypothesis regarding MetS as a consequence of a high intake in carbohydrates and food with a high glycemic index, particularly fructose, and relatively low intake of cholesterol and saturated fat. We support our arguments through animal studies which have shown that exposure of the liver to increased quantities of fructose leads to rapid stimulation of lipogenesis and accumulation of triglycerides. The adipocytes store triglycerides in lipid droplets, leading to adipocyte hypertrophy. Adipocyte hypertrophy is associated with macrophage accumulation in adipose tissue. An important modulator of obesity-associated macrophage responses in white adipose tissue is the death of adipocytes. Excess exposure to fructose intake determines the liver to metabolize high doses of fructose, producing increased levels of fructose end products, like glyceraldehyde and dihydroxyacetone phosphate, that can converge with the glycolytic pathway. Fructose also leads to increased levels of advanced glycation end products. The macrophages exposed to advanced glycation end products become dysfunctional and, on entry into the artery wall, contribute to plaque formation and thrombosis.
Arch Med Sci. 2011 Feb;7(1):8-20. Epub 2011 Mar 8.
Is the metabolic syndrome caused by a high fructose, and relatively low fat, low cholesterol diet?
Seneff S, Wainwright G, Mascitelli L.
Source
Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA, USA.
Abstract
The metabolic syndrome (MetS) is manifested by a lipid triad which includes elevated serum triglycerides, small LDL particles, and low high-density lipoprotein (HDL) cholesterol, by central obesity (central adiposity), insulin resistance, glucose intolerance and elevated blood pressure, and it is associated with an increased risk of type 2 diabetes and coronary heart disease. We have developed a new hypothesis regarding MetS as a consequence of a high intake in carbohydrates and food with a high glycemic index, particularly fructose, and relatively low intake of cholesterol and saturated fat. We support our arguments through animal studies which have shown that exposure of the liver to increased quantities of fructose leads to rapid stimulation of lipogenesis and accumulation of triglycerides. The adipocytes store triglycerides in lipid droplets, leading to adipocyte hypertrophy. Adipocyte hypertrophy is associated with macrophage accumulation in adipose tissue. An important modulator of obesity-associated macrophage responses in white adipose tissue is the death of adipocytes. Excess exposure to fructose intake determines the liver to metabolize high doses of fructose, producing increased levels of fructose end products, like glyceraldehyde and dihydroxyacetone phosphate, that can converge with the glycolytic pathway. Fructose also leads to increased levels of advanced glycation end products. The macrophages exposed to advanced glycation end products become dysfunctional and, on entry into the artery wall, contribute to plaque formation and thrombosis.
Fructose activates sweet taste receptors and synergizes with glucose to amplify insulin release
http://www.ncbi.nlm.nih.gov/pubmed/22315413
Proc Natl Acad Sci U S A. 2012 Feb 6. [Epub ahead of print]
Sweet taste receptor signaling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion.
Kyriazis GA, Soundarapandian MM, Tyrberg B.
Source
Metabolic Signaling and Disease, Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL 32827.
Abstract
Postprandial insulin release is regulated by glucose, but other circulating nutrients may target beta cells and potentiate glucose-stimulated insulin secretion via distinct signaling pathways. We demonstrate that fructose activates sweet taste receptors (TRs) on beta cells and synergizes with glucose to amplify insulin release in human and mouse islets. Genetic ablation of the sweet TR protein T1R2 obliterates fructose-induced insulin release and its potentiating effects on glucose-stimulated insulin secretion in vitro and in vivo. TR signaling in beta cells is triggered, at least in part, in parallel with the glucose metabolic pathway and leads to increases in intracellular calcium that are dependent on the activation of phospholipase C (PLC) and transient receptor potential cation channel, subfamily M, member 5 (TRPM5). Our results unveil a pathway for the regulation of insulin release by postprandial nutrients that involves beta cell sweet TR signaling.
Proc Natl Acad Sci U S A. 2012 Feb 6. [Epub ahead of print]
Sweet taste receptor signaling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion.
Kyriazis GA, Soundarapandian MM, Tyrberg B.
Source
Metabolic Signaling and Disease, Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL 32827.
Abstract
Postprandial insulin release is regulated by glucose, but other circulating nutrients may target beta cells and potentiate glucose-stimulated insulin secretion via distinct signaling pathways. We demonstrate that fructose activates sweet taste receptors (TRs) on beta cells and synergizes with glucose to amplify insulin release in human and mouse islets. Genetic ablation of the sweet TR protein T1R2 obliterates fructose-induced insulin release and its potentiating effects on glucose-stimulated insulin secretion in vitro and in vivo. TR signaling in beta cells is triggered, at least in part, in parallel with the glucose metabolic pathway and leads to increases in intracellular calcium that are dependent on the activation of phospholipase C (PLC) and transient receptor potential cation channel, subfamily M, member 5 (TRPM5). Our results unveil a pathway for the regulation of insulin release by postprandial nutrients that involves beta cell sweet TR signaling.
Factors related to quicker pulmonary exacerbation in adults with Cystic Fibrosis
http://www.ncbi.nlm.nih.gov/pubmed/22308550
Chron Respir Dis. 2012;9(1):9-16.
Factors associated with a shorter time until the next pulmonary exacerbation in adult patients with cystic fibrosis.
Sequeiros IM, Jarad N.
Source
Department of Respiratory Medicine, Bristol Royal Infirmary, Bristol, UK.
Abstract
Time until the subsequent exacerbation (PEx) in cystic fibrosis (CF) is a significant health outcome and one of the significant end points in clinical trials. Risk factors associated with shorter time until the next exacerbation (TUNE) have not been reported. This is a prospective study. TUNE was the number of days from the end of intravenous (IV) antibiotic treatment of a PEx until the day of start of IV antibiotics for the following PEx. Factors assessed were age, gender, site of treatment, CF-related diabetes (CFRD), allergic bronchopulmonary aspergillosis (ABPA) and infection with Pseudomonas aeruginosa (PA). In addition, we examined parameters obtained at day 14 of treatment including forced expiratory volume in the first second (FEV1), body mass index, CF respiratory symptom score, C-reactive protein (CRP) and serum cytokines. A total of 170 exacerbations in 58 adult CF patients (27 female), mean (SD) age 25.8 (6.7) years were analysed. When analysing individual variables, patients with lower FEV1, greater symptom score and higher CRP at the end of exacerbation were associated with shorter TUNE. Patients with ABPA and CFRD had a shorter TUNE than those without. When applying multiple regression analysis, factors associated with shorter TUNE were older age and lower day-14 FEV1 values. Shorter periods until the following PEx are expected in older CF patients and those with lower FEV1 at the end of course of treatment. When these risk factors are present, there may be a justification to take therapeutic steps to increase the time until the following PEx.
Chron Respir Dis. 2012;9(1):9-16.
Factors associated with a shorter time until the next pulmonary exacerbation in adult patients with cystic fibrosis.
Sequeiros IM, Jarad N.
Source
Department of Respiratory Medicine, Bristol Royal Infirmary, Bristol, UK.
Abstract
Time until the subsequent exacerbation (PEx) in cystic fibrosis (CF) is a significant health outcome and one of the significant end points in clinical trials. Risk factors associated with shorter time until the next exacerbation (TUNE) have not been reported. This is a prospective study. TUNE was the number of days from the end of intravenous (IV) antibiotic treatment of a PEx until the day of start of IV antibiotics for the following PEx. Factors assessed were age, gender, site of treatment, CF-related diabetes (CFRD), allergic bronchopulmonary aspergillosis (ABPA) and infection with Pseudomonas aeruginosa (PA). In addition, we examined parameters obtained at day 14 of treatment including forced expiratory volume in the first second (FEV1), body mass index, CF respiratory symptom score, C-reactive protein (CRP) and serum cytokines. A total of 170 exacerbations in 58 adult CF patients (27 female), mean (SD) age 25.8 (6.7) years were analysed. When analysing individual variables, patients with lower FEV1, greater symptom score and higher CRP at the end of exacerbation were associated with shorter TUNE. Patients with ABPA and CFRD had a shorter TUNE than those without. When applying multiple regression analysis, factors associated with shorter TUNE were older age and lower day-14 FEV1 values. Shorter periods until the following PEx are expected in older CF patients and those with lower FEV1 at the end of course of treatment. When these risk factors are present, there may be a justification to take therapeutic steps to increase the time until the following PEx.
From Children's Memorial-Chicago: Hispanic Cystic Fibrosis patients show low CFTR mutation rates
http://www.ncbi.nlm.nih.gov/pubmed/22311127
J Genet Couns. 2012 Feb 4. [Epub ahead of print]
Hispanic Infants with Cystic Fibrosis Show Low CFTR Mutation Detection Rates in the Illinois Newborn Screening Program.
Watts KD, Layne B, Harris A, McColley SA.
Source
The Division of Pulmonary Medicine, Children's Memorial Hospital, Chicago, IL, USA, kwatts@childrensmemorial.org.
Abstract
States develop specific protocols for cystic fibrosis (CF) newborn screening to reflect the population served. We hypothesized that mutation distribution and detection rates would differ between Hispanic and non-Hispanic CF patients diagnosed by IL newborn screen with more Hispanic infants carrying mutations not detected by the state panel. Data from CF cases diagnosed via newborn screen in IL between 3/1/2008 and 10/31/2010 were reviewed. More Hispanic infants with CF had one or more undefined mutations after screening, in comparison to non-Hispanic Caucasian patients (40% vs. 9.5%; p < 0.002). The risk of having a positive diagnosis of CF with only one mutation noted by positive newborn screen increases 2-fold in Hispanic Caucasian versus non-Hispanic Caucasian infants (5% vs. 2.4%). Health care providers must be aware of the limitations of CF newborn screening to ensure appropriate counseling and prompt referral for a positive newborn screen, even when zero or one mutations are identified.
J Genet Couns. 2012 Feb 4. [Epub ahead of print]
Hispanic Infants with Cystic Fibrosis Show Low CFTR Mutation Detection Rates in the Illinois Newborn Screening Program.
Watts KD, Layne B, Harris A, McColley SA.
Source
The Division of Pulmonary Medicine, Children's Memorial Hospital, Chicago, IL, USA, kwatts@childrensmemorial.org.
Abstract
States develop specific protocols for cystic fibrosis (CF) newborn screening to reflect the population served. We hypothesized that mutation distribution and detection rates would differ between Hispanic and non-Hispanic CF patients diagnosed by IL newborn screen with more Hispanic infants carrying mutations not detected by the state panel. Data from CF cases diagnosed via newborn screen in IL between 3/1/2008 and 10/31/2010 were reviewed. More Hispanic infants with CF had one or more undefined mutations after screening, in comparison to non-Hispanic Caucasian patients (40% vs. 9.5%; p < 0.002). The risk of having a positive diagnosis of CF with only one mutation noted by positive newborn screen increases 2-fold in Hispanic Caucasian versus non-Hispanic Caucasian infants (5% vs. 2.4%). Health care providers must be aware of the limitations of CF newborn screening to ensure appropriate counseling and prompt referral for a positive newborn screen, even when zero or one mutations are identified.
From U Washington/Seattle Children's: Future directions in Cystic Fibrosis research
http://www.ncbi.nlm.nih.gov/pubmed/22312017
Am J Respir Crit Care Med. 2012 Feb 3. [Epub ahead of print]
Future Directions in Early Cystic Fibrosis Lung Disease Research.
Ramsey BW, Banks-Schlegel S, Accurso FJ, Boucher RC, Cutting GR, Engelhardt JF, Guggino WB, Karp CL, Knowles MR, Kolls JK, Lipuma JJ, Lynch S, McCray Jr PB Jr, Rubenstein RC, Singh PK, Sorscher E, Welsh M.
Source
Seattle Children's Research Institute and University of Washington School of Medicine, Seattle, Washington, United States.
Abstract
Since the 1989 discovery that mutations in the CFTR gene cause cystic fibrosis (CF), there has been substantial progress towards understanding the molecular basis for CF lung disease leading to the discovery and development of new therapeutic approaches. However, the earliest impact of the loss of CFTR function on airway physiology and structure and its relationship to initial infection and inflammation is poorly understood. Universal newborn screening for CF in the United States represents an unprecedented opportunity for investigating CF clinical manifestations very early in life. Recently developed animal models with pulmonary phenotypic manifestations also provide a window into the early consequences of this genetic disorder. For these reasons, the National Heart, Lung, and Blood Institute (NHLBI) convened a working group of extramural experts, entitled "Future Research Directions in Early CF Lung Disease" on September 21-22, 2010, to identify future research directions of great promise in CF. The priority areas identified included: 1) exploring pathogenic mechanisms of early CF lung disease; 2) leveraging newborn screening to elucidate the natural history of early lung disease; 3) developing a spectrum of biomarkers of early lung disease that reflect CF pathophysiology, clinical outcome and response to treatment; 4) exploring the role of genetics/genomics (e.g., modifier genes, gene-environmental interactions, epigenetics, etc.) in early CF pathogenesis; 5) defining early microbiologic events in CF lung disease; and 6) elucidating the initial airway inflammatory, remodeling, and repair mechanisms in CF lung disease.
Am J Respir Crit Care Med. 2012 Feb 3. [Epub ahead of print]
Future Directions in Early Cystic Fibrosis Lung Disease Research.
Ramsey BW, Banks-Schlegel S, Accurso FJ, Boucher RC, Cutting GR, Engelhardt JF, Guggino WB, Karp CL, Knowles MR, Kolls JK, Lipuma JJ, Lynch S, McCray Jr PB Jr, Rubenstein RC, Singh PK, Sorscher E, Welsh M.
Source
Seattle Children's Research Institute and University of Washington School of Medicine, Seattle, Washington, United States.
Abstract
Since the 1989 discovery that mutations in the CFTR gene cause cystic fibrosis (CF), there has been substantial progress towards understanding the molecular basis for CF lung disease leading to the discovery and development of new therapeutic approaches. However, the earliest impact of the loss of CFTR function on airway physiology and structure and its relationship to initial infection and inflammation is poorly understood. Universal newborn screening for CF in the United States represents an unprecedented opportunity for investigating CF clinical manifestations very early in life. Recently developed animal models with pulmonary phenotypic manifestations also provide a window into the early consequences of this genetic disorder. For these reasons, the National Heart, Lung, and Blood Institute (NHLBI) convened a working group of extramural experts, entitled "Future Research Directions in Early CF Lung Disease" on September 21-22, 2010, to identify future research directions of great promise in CF. The priority areas identified included: 1) exploring pathogenic mechanisms of early CF lung disease; 2) leveraging newborn screening to elucidate the natural history of early lung disease; 3) developing a spectrum of biomarkers of early lung disease that reflect CF pathophysiology, clinical outcome and response to treatment; 4) exploring the role of genetics/genomics (e.g., modifier genes, gene-environmental interactions, epigenetics, etc.) in early CF pathogenesis; 5) defining early microbiologic events in CF lung disease; and 6) elucidating the initial airway inflammatory, remodeling, and repair mechanisms in CF lung disease.
From Thorax: Determining the optimal newborn screening protocol for Cystic Fibrosis
http://www.ncbi.nlm.nih.gov/pubmed/22318162
Thorax. 2012 Feb 8. [Epub ahead of print]
Determining the optimal newborn screening protocol for cystic fibrosis.
Southern KW.
Source
Department for Women's and Children's Health, University of Liverpool, Liverpool, UK.
"There is more published research examining newborn screening (NBS) for cystic fibrosis (CF) than for any other condition.1 Overall, the evidence for clinical benefit supports this strategy in an appropriate population with accessible healthcare provision.2 3 However, the evidence base is not as strong as one might expect, and this highlights the importance of ensuring that CF NBS programmes are designed and implemented in a rigorous and thoughtful manner that minimises potential distress for families.4 5"
Thorax. 2012 Feb 8. [Epub ahead of print]
Determining the optimal newborn screening protocol for cystic fibrosis.
Southern KW.
Source
Department for Women's and Children's Health, University of Liverpool, Liverpool, UK.
"There is more published research examining newborn screening (NBS) for cystic fibrosis (CF) than for any other condition.1 Overall, the evidence for clinical benefit supports this strategy in an appropriate population with accessible healthcare provision.2 3 However, the evidence base is not as strong as one might expect, and this highlights the importance of ensuring that CF NBS programmes are designed and implemented in a rigorous and thoughtful manner that minimises potential distress for families.4 5"
From Nature: "Drug bests Cystic Fibrosis mutation"
http://www.ncbi.nlm.nih.gov/pubmed/22318583
Nature. 2012 Feb 7;482(7384):145. doi: 10.1038/482145a.
Drug bests cystic-fibrosis mutation.
Ledford H.
Unfortunately, no abstract.
Nature. 2012 Feb 7;482(7384):145. doi: 10.1038/482145a.
Drug bests cystic-fibrosis mutation.
Ledford H.
Unfortunately, no abstract.
Cystic Fibrosis: Less invasive environmental strains of Burkholderia cenocepacia still effect epithelial integrity
http://www.ncbi.nlm.nih.gov/pubmed/22322958
Microbiology. 2012 Feb 9. [Epub ahead of print]
Interaction of environmental B. cenocepacia strains with cystic fibrosis and non-cystic fibrosis bronchial epithelial cells in vitro.
Bevivino A, Pirone L, Pilkington R, Cifani N, Dalmastri C, Callaghan M, Ascenzioni F, McClean S.
Source
ENEA Casaccia Research Center, Rome, Italy;
Abstract
Burkholderia cenocepacia is an important human pathogen in patients with cystic fibrosis (CF). Non-clinical reservoirs may play a role in the acquisition of infections, so it is important to evaluate the pathogenic potential of environmental B. cenocepacia isolates. In this study, we investigated the interactions of two environmental B. cenocepacia strains (Mex1 and MCII-168) with two bronchial epithelial cell lines, 16HBE14o- and CFBE41o-, which have a non-CF and a CF phenotype, respectively. The environmental strains showed a significantly lower level of invasion into both CF- and non-CF cells in comparison with the clinical B. cenocepacia LMG16656(T) strain. Exposure of polarized CFBE41o- or 16HBE14o- cells to the environmental strains resulted in a significant reduction in transepithelial resistance (TER), comparable to that observed following exposure to the clinical strain. A different mechanism of tight junction disruption in CF versus non-CF epithelia was found. In the 16HBE41o- cells, the environmental strains resulted in a drop in TER without any apparent effect on tight junction proteins such as zonula occludens-1 (ZO-1). In contrast, in CF cells, the amount of ZO-1 and its localisation were clearly altered by the presence of both the environmental strains, comparable to the effect of LMG16656. This study demonstrates that even if the environmental strains are significantly less invasive than the clinical strain, they have an effect on epithelial integrity comparable to that of the clinical strain. Finally, the tight junction regulatory protein ZO-1 appears to be more susceptible to the presence of environmental strains in CF cells than in the cells which express functional CFTR.
Microbiology. 2012 Feb 9. [Epub ahead of print]
Interaction of environmental B. cenocepacia strains with cystic fibrosis and non-cystic fibrosis bronchial epithelial cells in vitro.
Bevivino A, Pirone L, Pilkington R, Cifani N, Dalmastri C, Callaghan M, Ascenzioni F, McClean S.
Source
ENEA Casaccia Research Center, Rome, Italy;
Abstract
Burkholderia cenocepacia is an important human pathogen in patients with cystic fibrosis (CF). Non-clinical reservoirs may play a role in the acquisition of infections, so it is important to evaluate the pathogenic potential of environmental B. cenocepacia isolates. In this study, we investigated the interactions of two environmental B. cenocepacia strains (Mex1 and MCII-168) with two bronchial epithelial cell lines, 16HBE14o- and CFBE41o-, which have a non-CF and a CF phenotype, respectively. The environmental strains showed a significantly lower level of invasion into both CF- and non-CF cells in comparison with the clinical B. cenocepacia LMG16656(T) strain. Exposure of polarized CFBE41o- or 16HBE14o- cells to the environmental strains resulted in a significant reduction in transepithelial resistance (TER), comparable to that observed following exposure to the clinical strain. A different mechanism of tight junction disruption in CF versus non-CF epithelia was found. In the 16HBE41o- cells, the environmental strains resulted in a drop in TER without any apparent effect on tight junction proteins such as zonula occludens-1 (ZO-1). In contrast, in CF cells, the amount of ZO-1 and its localisation were clearly altered by the presence of both the environmental strains, comparable to the effect of LMG16656. This study demonstrates that even if the environmental strains are significantly less invasive than the clinical strain, they have an effect on epithelial integrity comparable to that of the clinical strain. Finally, the tight junction regulatory protein ZO-1 appears to be more susceptible to the presence of environmental strains in CF cells than in the cells which express functional CFTR.
Lung clearance index and early detection of Cystic Fibrosis lung disease
http://www.ncbi.nlm.nih.gov/pubmed/22323305
Am J Respir Crit Care Med. 2012 Feb 9. [Epub ahead of print]
Early Cystic Fibrosis Lung Disease Detected by Bronchoalveolar Lavage and Lung Clearance Index.
Belessis Y, Dixon B, Hawkins G, Pereira J, Peat J, Macdonald R, Field P, Numa A, Morton J, Lui K, Jaffe A.
Source
Department of Respiratory Medicine, Sydney Children's Hospital, Randwick, Sydney, New South Wales, Australia.
Abstract
RATIONALE:
Unrecognised airway infection and inflammation in young children with cystic fibrosis (CF) may lead to irreversible lung disease therefore early detection and treatment is highly desirable.
OBJECTIVES:
To determine whether the lung clearance index (LCI) is a sensitive and repeatable non-invasive measure of airway infection and inflammation in newborn-screened children with CF.
METHODS:
Forty-seven well children with CF (mean age, 1.55 years) and 25 healthy children (mean age, 1.26 years) underwent multiple-breath washout testing. LCI within and between-test variability was assessed. Children with CF also had surveillance bronchoalveolar lavage (BAL) performed.
MEASUREMENTS AND
MAIN RESULTS:
Mean (SD) LCI in healthy children was 6.45 (0.49). LCI was higher in children with CF, 7.21 (0.81), P < 0.001. The upper limit of normal for LCI was 7.41. Fifteen (32%) children with CF had an elevated LCI. LCI measurements were repeatable and reproducible. Airway infection was present in 17 (36%) children with CF including 7 (15%) with Pseudomonas aeruginosa. Polymicrobial growth was associated with worse inflammation. LCI was higher in children with Pseudomonas, 7.92 (1.16), than in children without Pseudomonas, 7.02 (0.56), P = 0.038. LCI correlated with BAL interleukin-8, R2 =0.20, P =0.004 and neutrophil count R2 =0.21, P =0.001. A LCI below the upper limit of normality had a high negative predictive value (93%) in excluding Pseudomonas.
CONCLUSIONS:
LCI is elevated early in CF especially in the presence of Pseudomonas and airway inflammation. LCI is a feasible, repeatable and sensitive non-invasive marker of lung disease in young children with CF.
Am J Respir Crit Care Med. 2012 Feb 9. [Epub ahead of print]
Early Cystic Fibrosis Lung Disease Detected by Bronchoalveolar Lavage and Lung Clearance Index.
Belessis Y, Dixon B, Hawkins G, Pereira J, Peat J, Macdonald R, Field P, Numa A, Morton J, Lui K, Jaffe A.
Source
Department of Respiratory Medicine, Sydney Children's Hospital, Randwick, Sydney, New South Wales, Australia.
Abstract
RATIONALE:
Unrecognised airway infection and inflammation in young children with cystic fibrosis (CF) may lead to irreversible lung disease therefore early detection and treatment is highly desirable.
OBJECTIVES:
To determine whether the lung clearance index (LCI) is a sensitive and repeatable non-invasive measure of airway infection and inflammation in newborn-screened children with CF.
METHODS:
Forty-seven well children with CF (mean age, 1.55 years) and 25 healthy children (mean age, 1.26 years) underwent multiple-breath washout testing. LCI within and between-test variability was assessed. Children with CF also had surveillance bronchoalveolar lavage (BAL) performed.
MEASUREMENTS AND
MAIN RESULTS:
Mean (SD) LCI in healthy children was 6.45 (0.49). LCI was higher in children with CF, 7.21 (0.81), P < 0.001. The upper limit of normal for LCI was 7.41. Fifteen (32%) children with CF had an elevated LCI. LCI measurements were repeatable and reproducible. Airway infection was present in 17 (36%) children with CF including 7 (15%) with Pseudomonas aeruginosa. Polymicrobial growth was associated with worse inflammation. LCI was higher in children with Pseudomonas, 7.92 (1.16), than in children without Pseudomonas, 7.02 (0.56), P = 0.038. LCI correlated with BAL interleukin-8, R2 =0.20, P =0.004 and neutrophil count R2 =0.21, P =0.001. A LCI below the upper limit of normality had a high negative predictive value (93%) in excluding Pseudomonas.
CONCLUSIONS:
LCI is elevated early in CF especially in the presence of Pseudomonas and airway inflammation. LCI is a feasible, repeatable and sensitive non-invasive marker of lung disease in young children with CF.
Transmittable strains of Psudomonas in Cystic Fibrosis lung infections
http://www.ncbi.nlm.nih.gov/pubmed/22323572
Eur Respir J. 2012 Feb 9. [Epub ahead of print]
Transmissible strains of Pseudomonas aeruginosa in Cystic Fibrosis lung infections.
Fothergill JL, Walshaw MJ, Winstanley C.
Source
University of Liverpool, UK.
Abstract
Pseudomonas aeruginosa chronic lung infections are the major cause of morbidity and mortality associated with cystic fibrosis (CF). For many years, the consensus was that CF patients acquire P. aeruginosa from the environment, and hence harbour their own individual clones. However, in the last 15 years the emergence of transmissible strains, in some cases associated with greater morbidity and increased antimicrobial resistance, has changed the way that many clinics treat their patients. Here we provide a summary of reported transmissible strains in the United Kingdom, other parts of Europe, Australia and North America. In particular, we discuss the prevalence, epidemiology, unusual genotypic and phenotypic features and virulence of the most intensively studied transmissible strain, the Liverpool Epidemic Strain. We also discuss the clinical impact of transmissible strains, in particular the diagnostic and infection control approaches adopted to counter their spread. Genomic analysis carried out so far has provided little evidence that transmissibility is due to shared genetic characteristics between different strains. Previous experiences with transmissible strains should help us to learn lessons for the future. In particular, there is a clear need for strain surveillance if emerging problem strains are to be detected before they are widely transmitted.
Eur Respir J. 2012 Feb 9. [Epub ahead of print]
Transmissible strains of Pseudomonas aeruginosa in Cystic Fibrosis lung infections.
Fothergill JL, Walshaw MJ, Winstanley C.
Source
University of Liverpool, UK.
Abstract
Pseudomonas aeruginosa chronic lung infections are the major cause of morbidity and mortality associated with cystic fibrosis (CF). For many years, the consensus was that CF patients acquire P. aeruginosa from the environment, and hence harbour their own individual clones. However, in the last 15 years the emergence of transmissible strains, in some cases associated with greater morbidity and increased antimicrobial resistance, has changed the way that many clinics treat their patients. Here we provide a summary of reported transmissible strains in the United Kingdom, other parts of Europe, Australia and North America. In particular, we discuss the prevalence, epidemiology, unusual genotypic and phenotypic features and virulence of the most intensively studied transmissible strain, the Liverpool Epidemic Strain. We also discuss the clinical impact of transmissible strains, in particular the diagnostic and infection control approaches adopted to counter their spread. Genomic analysis carried out so far has provided little evidence that transmissibility is due to shared genetic characteristics between different strains. Previous experiences with transmissible strains should help us to learn lessons for the future. In particular, there is a clear need for strain surveillance if emerging problem strains are to be detected before they are widely transmitted.
From Science: Cystic Fibrosis and personalized medicine. Upcoming cost-benefit analyses will be painful
http://www.ncbi.nlm.nih.gov/pubmed/22323790
Science. 2012 Feb 10;335(6069):645.
Personalized medicine. New cystic fibrosis drug offers hope, at a price.
Kaiser J.
"Last week, U.S. regulators approved a new drug for cystic fibrosis (CF). The drug, called Kalydeco and made by Vertex Pharmaceuticals, is the first to target the genetic defect discovered 23 years ago that causes a protein to malfunction in CF, resulting in a sticky buildup of mucus in the lungs and digestive tract that eventually causes fatal health problems. But the approval of Kalydeco illustrates both the promise and peril of personalized medicine, which in this case has resulted in a drug that's extremely expensive and helps only 4% of people with the disease, or 1200 patients."
Science. 2012 Feb 10;335(6069):645.
Personalized medicine. New cystic fibrosis drug offers hope, at a price.
Kaiser J.
"Last week, U.S. regulators approved a new drug for cystic fibrosis (CF). The drug, called Kalydeco and made by Vertex Pharmaceuticals, is the first to target the genetic defect discovered 23 years ago that causes a protein to malfunction in CF, resulting in a sticky buildup of mucus in the lungs and digestive tract that eventually causes fatal health problems. But the approval of Kalydeco illustrates both the promise and peril of personalized medicine, which in this case has resulted in a drug that's extremely expensive and helps only 4% of people with the disease, or 1200 patients."
Antibiotic susceptibility patterns for Pseudomonas in adults with and without Cystic Fibrosis
http://www.ncbi.nlm.nih.gov/pubmed/22325689
J Cyst Fibros. 2012 Feb 9. [Epub ahead of print]
Comparison of antibiotic susceptibility patterns in Pseudomonas aeruginosa isolated from adult patients with cystic fibrosis (CF) with invasive Pseudomonas aeruginosa from non-CF patients.
Rao P, McCaughan J, McCalmont M, Goldsmith CE, Hall V, Millar BC, McCann MA, Downey DG, Rendall JC, Elborn JS, Moore JE.
Source
Northern Ireland Public Health Laboratory, Department of Bacteriology, Belfast City Hospital, Lisburn Road, Belfast, Northern Ireland, BT9 7AD, UK; Bloomfield Collegiate, Astoria Gardens, Belfast, Northern Ireland, BT5 6HW, UK.
Interesting article; unfortunately no abstract.
J Cyst Fibros. 2012 Feb 9. [Epub ahead of print]
Comparison of antibiotic susceptibility patterns in Pseudomonas aeruginosa isolated from adult patients with cystic fibrosis (CF) with invasive Pseudomonas aeruginosa from non-CF patients.
Rao P, McCaughan J, McCalmont M, Goldsmith CE, Hall V, Millar BC, McCann MA, Downey DG, Rendall JC, Elborn JS, Moore JE.
Source
Northern Ireland Public Health Laboratory, Department of Bacteriology, Belfast City Hospital, Lisburn Road, Belfast, Northern Ireland, BT9 7AD, UK; Bloomfield Collegiate, Astoria Gardens, Belfast, Northern Ireland, BT5 6HW, UK.
Interesting article; unfortunately no abstract.
From J Cystic Fibrosis: Genetic counseling difficulties due to novel CFTR gene mutations
http://www.ncbi.nlm.nih.gov/pubmed/22326559
J Cyst Fibros. 2012 Feb 11. [Epub ahead of print]
Cystic fibrosis genetic counseling difficulties due to the identification of novel mutations in the CFTR gene.
Poulou M, Fylaktou I, Fotoulaki M, Kanavakis E, Tzetis M.
Source
Department of Medical Genetics, Medical School, University of Athens, Greece.
Abstract
BACKGROUND:
The Cystic Fibrosis database includes amongst the 1893 gene mutations and polymorphisms a lot of missense mutations, the disease status of which still remains unproven. In populations with high rates of CFTR mutation heterogeneity, molecular diagnosis is difficult often causing counseling difficulties especially in cases of rare and/or novel mutations.
METHODS:
Approaches to counseling in cases of novel variants.
RESULTS:
Thirty-seven novel variants (4 synonymous, 24 missense, 2 frameshift and 10 intronic substitutions) were identified and evaluated with the help of in silico tools.
CONCLUSIONS:
In a diagnostic environment the answers have to be given within a specific timeframe, the in silico tools in combination with the phenotype offer some help but their diagnostic value is limited and cannot be used in isolation for the determination of the severity of the mutation.
J Cyst Fibros. 2012 Feb 11. [Epub ahead of print]
Cystic fibrosis genetic counseling difficulties due to the identification of novel mutations in the CFTR gene.
Poulou M, Fylaktou I, Fotoulaki M, Kanavakis E, Tzetis M.
Source
Department of Medical Genetics, Medical School, University of Athens, Greece.
Abstract
BACKGROUND:
The Cystic Fibrosis database includes amongst the 1893 gene mutations and polymorphisms a lot of missense mutations, the disease status of which still remains unproven. In populations with high rates of CFTR mutation heterogeneity, molecular diagnosis is difficult often causing counseling difficulties especially in cases of rare and/or novel mutations.
METHODS:
Approaches to counseling in cases of novel variants.
RESULTS:
Thirty-seven novel variants (4 synonymous, 24 missense, 2 frameshift and 10 intronic substitutions) were identified and evaluated with the help of in silico tools.
CONCLUSIONS:
In a diagnostic environment the answers have to be given within a specific timeframe, the in silico tools in combination with the phenotype offer some help but their diagnostic value is limited and cannot be used in isolation for the determination of the severity of the mutation.
Evaluating cross-sectional area of the trachea in children with Cystic Fibrosis
http://www.ncbi.nlm.nih.gov/pubmed/22326722
Respir Physiol Neurobiol. 2012 Feb 6. [Epub ahead of print]
Evaluation of the trachea and intrathoracic airways by the acoustic reflection method in children with cystic fibrosis.
Leboulanger N, Louis B, Corvol H, Ramirez A, Fodil R, Lofaso F, Fauroux B.
Source
UPMC University Paris 06, France; Otolaryngology-Head and Neck Surgery Department, AP-HP, Armand-Trousseau Children's Hospital, 26 Avenue du Dr Arnold Netter, 75012 Paris, France; INSERM, Unité U955, 94010 Créteil, France; INSERM UMR S-938, 75012 Paris, France.
Abstract
Tracheomalacia has been observed in older patients with cystic fibrosis (CF). The acoustic reflection method (ARM) allows a noninvasive calculation of the longitudinal cross-sectional area of the trachea (MTAv) and the airway resistance (Raw). ARM measurements were performed in 20 CF children and 20 controls during spontaneous breathing (SB), forced inspiration (FI), and forced expiration (FE). The mean MTAv value was comparable in the CF patients and the control subjects during SB, FI, and FE. The Raw was also comparable during SB and FI. However, the Raw during FE was higher in the CF patients than in the control subjects (7.9±2.3 vs 5.0±1.5cmH(2)Ol(-1)s(-1), respectively, p<0.001). In the patients with CF, only the Raw during FE correlated with the predicted forced expiratory volume in 1s (R(2)=0.37, p=0.04). The tracheal cross-sectional area measured by the ARM is normal in children with CF but the increase in Raw during FE suggests an increase in intrathoracic airway distensibility.
Respir Physiol Neurobiol. 2012 Feb 6. [Epub ahead of print]
Evaluation of the trachea and intrathoracic airways by the acoustic reflection method in children with cystic fibrosis.
Leboulanger N, Louis B, Corvol H, Ramirez A, Fodil R, Lofaso F, Fauroux B.
Source
UPMC University Paris 06, France; Otolaryngology-Head and Neck Surgery Department, AP-HP, Armand-Trousseau Children's Hospital, 26 Avenue du Dr Arnold Netter, 75012 Paris, France; INSERM, Unité U955, 94010 Créteil, France; INSERM UMR S-938, 75012 Paris, France.
Abstract
Tracheomalacia has been observed in older patients with cystic fibrosis (CF). The acoustic reflection method (ARM) allows a noninvasive calculation of the longitudinal cross-sectional area of the trachea (MTAv) and the airway resistance (Raw). ARM measurements were performed in 20 CF children and 20 controls during spontaneous breathing (SB), forced inspiration (FI), and forced expiration (FE). The mean MTAv value was comparable in the CF patients and the control subjects during SB, FI, and FE. The Raw was also comparable during SB and FI. However, the Raw during FE was higher in the CF patients than in the control subjects (7.9±2.3 vs 5.0±1.5cmH(2)Ol(-1)s(-1), respectively, p<0.001). In the patients with CF, only the Raw during FE correlated with the predicted forced expiratory volume in 1s (R(2)=0.37, p=0.04). The tracheal cross-sectional area measured by the ARM is normal in children with CF but the increase in Raw during FE suggests an increase in intrathoracic airway distensibility.
From U Paris-Sud, Orsay: MLVA, epidemiology, and Cystic Fibrosis
http://www.ncbi.nlm.nih.gov/pubmed/22327344
Eur J Clin Microbiol Infect Dis. 2012 Feb 11. [Epub ahead of print]
A new highly discriminatory multiplex capillary-based MLVA assay as a tool for the epidemiological survey of Pseudomonas aeruginosa in cystic fibrosis patients.
Sobral D, Mariani-Kurkdjian P, Bingen E, Vu-Thien H, Hormigos K, Lebeau B, Loisy-Hamon F, Munck A, Vergnaud G, Pourcel C.
Source
Institut de Génétique et Microbiologie, University Paris-Sud, UMR 8621, 91405, Orsay, France.
Abstract
Multiple locus variable number of tandem repeats (VNTR) analysis (MLVA) has been shown to provide a high level of information for epidemiological investigations and the follow-up of Pseudomonas aeruginosa chronic infection. In the present study, an automatized MLVA assay has been developed for the analysis of 16 VNTRs in two multiplex polymerase chain reactions (PCRs), followed by capillary electrophoresis. The result in the form of a code is directly usable for clustering analyses. This MLVA-16(Orsay) scheme was applied to the genotyping of 83 isolates from eight cystic fibrosis patients, demonstrating that the same genotype persisted during eight years of chronic infection in the majority of cases. Comparison with pulsed-field gel electrophoresis (PFGE) analysis showed that both methods were congruent, MLVA providing, in some cases, additional informativity. The evolution of strains during long-term infection was revealed by the presence of VNTR variants.
Eur J Clin Microbiol Infect Dis. 2012 Feb 11. [Epub ahead of print]
A new highly discriminatory multiplex capillary-based MLVA assay as a tool for the epidemiological survey of Pseudomonas aeruginosa in cystic fibrosis patients.
Sobral D, Mariani-Kurkdjian P, Bingen E, Vu-Thien H, Hormigos K, Lebeau B, Loisy-Hamon F, Munck A, Vergnaud G, Pourcel C.
Source
Institut de Génétique et Microbiologie, University Paris-Sud, UMR 8621, 91405, Orsay, France.
Abstract
Multiple locus variable number of tandem repeats (VNTR) analysis (MLVA) has been shown to provide a high level of information for epidemiological investigations and the follow-up of Pseudomonas aeruginosa chronic infection. In the present study, an automatized MLVA assay has been developed for the analysis of 16 VNTRs in two multiplex polymerase chain reactions (PCRs), followed by capillary electrophoresis. The result in the form of a code is directly usable for clustering analyses. This MLVA-16(Orsay) scheme was applied to the genotyping of 83 isolates from eight cystic fibrosis patients, demonstrating that the same genotype persisted during eight years of chronic infection in the majority of cases. Comparison with pulsed-field gel electrophoresis (PFGE) analysis showed that both methods were congruent, MLVA providing, in some cases, additional informativity. The evolution of strains during long-term infection was revealed by the presence of VNTR variants.
From Thorax: Genetic studies for primary ciliary dyskinesia
http://www.ncbi.nlm.nih.gov/pubmed/22328589
Thorax. 2012 Feb 10. [Epub ahead of print]
Cutting edge genetic studies in primary ciliary dyskinesia.
Knowles MR, Leigh MW, Zariwala MA.
Source
Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
"We would describe our genetic studies in primary ciliary dyskinesia1 as ‘cutting edge’, rather than ‘beyond the fringe’.2 Indeed, we predict that in 5 years genetic testing will be more readily available and used worldwide for diagnostic studies in primary ciliary dyskinesia than high speed ciliary waveform analysis."
Thorax. 2012 Feb 10. [Epub ahead of print]
Cutting edge genetic studies in primary ciliary dyskinesia.
Knowles MR, Leigh MW, Zariwala MA.
Source
Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
"We would describe our genetic studies in primary ciliary dyskinesia1 as ‘cutting edge’, rather than ‘beyond the fringe’.2 Indeed, we predict that in 5 years genetic testing will be more readily available and used worldwide for diagnostic studies in primary ciliary dyskinesia than high speed ciliary waveform analysis."
Pediatric lung involvement with Langerhans Cell Histiocytosis
http://www.ncbi.nlm.nih.gov/pubmed/22284564
J Pediatr. 2012 Jan 26. [Epub ahead of print]
Pulmonary Involvement in Pediatric-Onset Multisystem Langerhans Cell Histiocytosis: Effect on Course and Outcome.
Ronceray L, Pötschger U, Janka G, Gadner H, Minkov M; German Society for Pediatric Hematology and Oncology, Langerhans Cell Histiocytosis Study Group.
Source
Children's Cancer Research Institute, Vienna, Austria.
Abstract
OBJECTIVES:
To assess the effect of pulmonary involvement on the course and outcome of multisystem Langerhans cell histiocytosis (MS-LCH) in children.
STUDY DESIGN:
We conducted a retrospective analysis of 420 consecutive patients with MS-LCH. In this analysis, the term "risk organs" is defined as involvement of the liver, spleen, and/or hematopoietic system. The effect of pulmonary involvement on survival was assessed with multivariate Cox regression with adjustment for risk organs involvement and age.
RESULTS:
Pulmonary involvement in MS-LCH was present at diagnosis in 102 patients (24%). Of the 318 patients without pulmonary involvement at diagnosis, it developed in 28 within a median of 10 months (range, 1 month-5.5 years). The 5-year overall survival rate in patients without risk organ involvement at diagnosis was 96% in patients without pulmonary involvement and 94% in those with pulmonary involvement. In patients with risk organ involvement at diagnosis, the 5-year overall survival rate was 73% in patients without pulmonary involvement and 65% in patients with pulmonary involvement. In multivariate analysis, pulmonary involvement at diagnosis had no significant impact on survival rats (P = .109, hazard ratio = 1.5).
CONCLUSIONS:
In multivariate analysis, pulmonary involvement was not an independent prognostic variable and should therefore be excluded from the definition of risk organ involvement in MS-LCH.
J Pediatr. 2012 Jan 26. [Epub ahead of print]
Pulmonary Involvement in Pediatric-Onset Multisystem Langerhans Cell Histiocytosis: Effect on Course and Outcome.
Ronceray L, Pötschger U, Janka G, Gadner H, Minkov M; German Society for Pediatric Hematology and Oncology, Langerhans Cell Histiocytosis Study Group.
Source
Children's Cancer Research Institute, Vienna, Austria.
Abstract
OBJECTIVES:
To assess the effect of pulmonary involvement on the course and outcome of multisystem Langerhans cell histiocytosis (MS-LCH) in children.
STUDY DESIGN:
We conducted a retrospective analysis of 420 consecutive patients with MS-LCH. In this analysis, the term "risk organs" is defined as involvement of the liver, spleen, and/or hematopoietic system. The effect of pulmonary involvement on survival was assessed with multivariate Cox regression with adjustment for risk organs involvement and age.
RESULTS:
Pulmonary involvement in MS-LCH was present at diagnosis in 102 patients (24%). Of the 318 patients without pulmonary involvement at diagnosis, it developed in 28 within a median of 10 months (range, 1 month-5.5 years). The 5-year overall survival rate in patients without risk organ involvement at diagnosis was 96% in patients without pulmonary involvement and 94% in those with pulmonary involvement. In patients with risk organ involvement at diagnosis, the 5-year overall survival rate was 73% in patients without pulmonary involvement and 65% in patients with pulmonary involvement. In multivariate analysis, pulmonary involvement at diagnosis had no significant impact on survival rats (P = .109, hazard ratio = 1.5).
CONCLUSIONS:
In multivariate analysis, pulmonary involvement was not an independent prognostic variable and should therefore be excluded from the definition of risk organ involvement in MS-LCH.
Wednesday, February 15, 2012
PRAME and differentiating serous carcinoma from mesothelioma
http://www.ncbi.nlm.nih.gov/pubmed/22261449
Am J Clin Pathol. 2012 Feb;137(2):240-7.
PRAME (Preferentially Expressed Antigen of Melanoma) Is a Novel Marker for Differentiating Serous Carcinoma From Malignant Mesothelioma.
Brenne K, Nymoen DA, Reich R, Davidson B.
Source
Dept of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Montebello N-0310 Oslo, Norway.
Abstract
The PRAME (preferentially expressed antigen of melanoma) gene was previously shown to be overexpressed in ovarian/primary peritoneal serous carcinoma compared with malignant mesothelioma using gene expression arrays. The objective of this study was to validate this finding at the messenger RNA (mRNA) and protein levels. Quantitative real-time polymerase chain reaction analysis of 126 müllerian carcinomas and 23 malignant mesotheliomas showed significantly higher PRAME mRNA expression in the former tumor (P < .001; test sensitivity and specificity, 89% and 91%, respectively). PRAME protein was expressed in 41 of 50 müllerian carcinomas and 0 of 30 mesotheliomas using Western blotting (P < .001; test sensitivity and specificity, 82% and 100%, respectively). PRAME levels in müllerian carcinoma were unrelated to survival; however, PRAME protein expression was up-regulated in solid metastases compared with primary carcinoma and effusions (P < .001). Our data confirm that PRAME effectively differentiates müllerian carcinoma from malignant mesothelioma at the mRNA and protein levels, suggesting a role in the diagnostic workup of serosal cancers.
Am J Clin Pathol. 2012 Feb;137(2):240-7.
PRAME (Preferentially Expressed Antigen of Melanoma) Is a Novel Marker for Differentiating Serous Carcinoma From Malignant Mesothelioma.
Brenne K, Nymoen DA, Reich R, Davidson B.
Source
Dept of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Montebello N-0310 Oslo, Norway.
Abstract
The PRAME (preferentially expressed antigen of melanoma) gene was previously shown to be overexpressed in ovarian/primary peritoneal serous carcinoma compared with malignant mesothelioma using gene expression arrays. The objective of this study was to validate this finding at the messenger RNA (mRNA) and protein levels. Quantitative real-time polymerase chain reaction analysis of 126 müllerian carcinomas and 23 malignant mesotheliomas showed significantly higher PRAME mRNA expression in the former tumor (P < .001; test sensitivity and specificity, 89% and 91%, respectively). PRAME protein was expressed in 41 of 50 müllerian carcinomas and 0 of 30 mesotheliomas using Western blotting (P < .001; test sensitivity and specificity, 82% and 100%, respectively). PRAME levels in müllerian carcinoma were unrelated to survival; however, PRAME protein expression was up-regulated in solid metastases compared with primary carcinoma and effusions (P < .001). Our data confirm that PRAME effectively differentiates müllerian carcinoma from malignant mesothelioma at the mRNA and protein levels, suggesting a role in the diagnostic workup of serosal cancers.
Asbestos fiber burden and mesothelioma in patients who lived near asbestos-cement factories
http://www.ncbi.nlm.nih.gov/pubmed/22247179
Ann Occup Hyg. 2012 Jan 12. [Epub ahead of print]
Asbestos Fibre Burden in the Lungs of Patients with Mesothelioma Who Lived Near Asbestos-Cement Factories.
Barbieri PG, Mirabelli D, Somigliana A, Cavone D, Merler E.
Source
Mesothelioma Registry, Occupational Health Unit, Local Health Authority, 25128 Brescia, Italy.
Abstract
BackgroundEpidemics of malignant mesothelioma are occurring among inhabitants of Casale Monferrato and Bari never employed in the local asbestos-cement (AC) factories. The mesothelioma risk increased with proximity of residence to both plants.ObjectivesTo provide information on the intensity of environmental asbestos exposure, in the general population living around these factories, through the evaluation of the lung fibre burden in mesothelioma patients.MethodsWe analysed by a scanning electron microscope equipped with X-ray microanalysis wet (formalin-fixed) lung tissue samples from eight mesothelioma patients who lived in Casale Monferrato or Bari and underwent surgery. Their occupational and residential history was obtained during face-to-face interviews. Semi-quantitative and quantitative indices of cumulative environmental exposure to asbestos were computed, based on residential distance from the AC plants and duration of stay.ResultsThe lung fibre burden ranged from 110 000 to 4 300 000 fibres per gram of dry lung (f/g) and was >1 000 000 f/g in three subjects. In four cases, only amphibole fibres were detected. Environmental exposures had ceased at least 10 years before samples were taken. No patient had other definite or probable asbestos exposures. A linear relationship was observed between the lung fibre burden and all three indices of environmental cumulative exposure to asbestos.ConclusionsEnvironmental exposure to a mixture of asbestos fibres may lead to a high lung fibre burden of amphiboles years after exposure cessation. The epidemiological evidence of an increased mesothelioma risk for the general population of Casale Monferrato and Bari, associated with asbestos contamination of the living environment, is corroborated.
Ann Occup Hyg. 2012 Jan 12. [Epub ahead of print]
Asbestos Fibre Burden in the Lungs of Patients with Mesothelioma Who Lived Near Asbestos-Cement Factories.
Barbieri PG, Mirabelli D, Somigliana A, Cavone D, Merler E.
Source
Mesothelioma Registry, Occupational Health Unit, Local Health Authority, 25128 Brescia, Italy.
Abstract
BackgroundEpidemics of malignant mesothelioma are occurring among inhabitants of Casale Monferrato and Bari never employed in the local asbestos-cement (AC) factories. The mesothelioma risk increased with proximity of residence to both plants.ObjectivesTo provide information on the intensity of environmental asbestos exposure, in the general population living around these factories, through the evaluation of the lung fibre burden in mesothelioma patients.MethodsWe analysed by a scanning electron microscope equipped with X-ray microanalysis wet (formalin-fixed) lung tissue samples from eight mesothelioma patients who lived in Casale Monferrato or Bari and underwent surgery. Their occupational and residential history was obtained during face-to-face interviews. Semi-quantitative and quantitative indices of cumulative environmental exposure to asbestos were computed, based on residential distance from the AC plants and duration of stay.ResultsThe lung fibre burden ranged from 110 000 to 4 300 000 fibres per gram of dry lung (f/g) and was >1 000 000 f/g in three subjects. In four cases, only amphibole fibres were detected. Environmental exposures had ceased at least 10 years before samples were taken. No patient had other definite or probable asbestos exposures. A linear relationship was observed between the lung fibre burden and all three indices of environmental cumulative exposure to asbestos.ConclusionsEnvironmental exposure to a mixture of asbestos fibres may lead to a high lung fibre burden of amphiboles years after exposure cessation. The epidemiological evidence of an increased mesothelioma risk for the general population of Casale Monferrato and Bari, associated with asbestos contamination of the living environment, is corroborated.
CT-derived mesothelioma tumor volume and survival
http://www.ncbi.nlm.nih.gov/pubmed/22268178
AJR Am J Roentgenol. 2012 Feb;198(2):359-63.
Epithelial Malignant Pleural Mesothelioma After Extrapleural Pneumonectomy: Stratification of Survival With CT-Derived Tumor Volume.
Gill RR, Richards WG, Yeap BY, Matsuoka S, Wolf AS, Gerbaudo VH, Bueno R, Sugarbaker DJ, Hatabu H.
Source
Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115.
Abstract
OBJECTIVE:
The purpose of this study was to assess the usefulness of CT-derived tumor volume, with control for other prognostic factors, for stratifying survival after surgery-based multimodality treatment of a large cohort of patients with epithelial malignant pleural mesothelioma.
MATERIALS AND METHODS:
We retrospectively reviewed 338 patients with mesothelioma who underwent extrapleural pneumonectomy between 2001 and 2007. The study cohort comprised 88 patients with epithelial subtype tumors, DICOM-format CT scans, and data regarding neoadjuvant and adjuvant therapy. Tumor volume was calculated, and Kaplan-Meier survival and Cox regression analyses were performed to compare the estimated survival functions of patient subgroups based on volume and other covariates related to outcome (sex, age, preoperative platelet count, hemoglobin concentration, WBC count, clinical and pathologic TNM category, and administration of neoadjuvant and adjuvant therapy). A multivariate regression model was derived on the basis of the most significant univariate predictors.
RESULTS:
The median estimated tumor volume was 319 cm(3) (range, 4-3256 cm(3)). In univariate analysis, tumor volume, hemoglobin concentration, platelet count, pathologic TNM category, and administration of adjuvant chemotherapy or radiation therapy met the criteria for inclusion in the reverse stepwise regression analysis. In the final model, tumor volume, hemoglobin concentration, and administration of adjuvant chemotherapy or radiotherapy were identified as independently associated with overall survival.
CONCLUSION:
With control of prognostic covariates, CT-derived tumor volume can be used to stratify survival of patients with epithelial mesothelioma after extrapleural pneumonectomy and should be included in prognostic evaluation of patients for whom resection is being considered.
AJR Am J Roentgenol. 2012 Feb;198(2):359-63.
Epithelial Malignant Pleural Mesothelioma After Extrapleural Pneumonectomy: Stratification of Survival With CT-Derived Tumor Volume.
Gill RR, Richards WG, Yeap BY, Matsuoka S, Wolf AS, Gerbaudo VH, Bueno R, Sugarbaker DJ, Hatabu H.
Source
Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115.
Abstract
OBJECTIVE:
The purpose of this study was to assess the usefulness of CT-derived tumor volume, with control for other prognostic factors, for stratifying survival after surgery-based multimodality treatment of a large cohort of patients with epithelial malignant pleural mesothelioma.
MATERIALS AND METHODS:
We retrospectively reviewed 338 patients with mesothelioma who underwent extrapleural pneumonectomy between 2001 and 2007. The study cohort comprised 88 patients with epithelial subtype tumors, DICOM-format CT scans, and data regarding neoadjuvant and adjuvant therapy. Tumor volume was calculated, and Kaplan-Meier survival and Cox regression analyses were performed to compare the estimated survival functions of patient subgroups based on volume and other covariates related to outcome (sex, age, preoperative platelet count, hemoglobin concentration, WBC count, clinical and pathologic TNM category, and administration of neoadjuvant and adjuvant therapy). A multivariate regression model was derived on the basis of the most significant univariate predictors.
RESULTS:
The median estimated tumor volume was 319 cm(3) (range, 4-3256 cm(3)). In univariate analysis, tumor volume, hemoglobin concentration, platelet count, pathologic TNM category, and administration of adjuvant chemotherapy or radiation therapy met the criteria for inclusion in the reverse stepwise regression analysis. In the final model, tumor volume, hemoglobin concentration, and administration of adjuvant chemotherapy or radiotherapy were identified as independently associated with overall survival.
CONCLUSION:
With control of prognostic covariates, CT-derived tumor volume can be used to stratify survival of patients with epithelial mesothelioma after extrapleural pneumonectomy and should be included in prognostic evaluation of patients for whom resection is being considered.
From Eur Respir J: Mesothelioma incidence projections in SE England
http://www.ncbi.nlm.nih.gov/pubmed/22282545
Eur Respir J. 2012 Jan 26. [Epub ahead of print]
Mesothelioma incidence projections in South East England.
Riaz SP, Coupland VH, Lüchtenborg M, Peake MD, Møller H.
Source
Thames Cancer Registry, 1st Floor, Capital House, 42 Weston Street, London SE1 3QD.
Abstract
We estimated the past and future age-standardised incidence rates of mesothelioma by birth cohort and by period of diagnosis in South East England.We extracted data on patients diagnosed with mesothelioma (ICD-10 C45) between 1960 and 2009 from the Thames Cancer Registry. We calculated the age-standardised incidence rates using the European standard population. We used age-cohort and age-period modelling to estimate the age-specific incidence rates for the 1900 to 1950 birth cohorts and the 1935 to 2034 calendar periods.A much more pronounced increase in mesothelioma incidence between 1972 and 2007 was observed in males than in females. In both sexes, the incidence rates increased in successive generations up to the 1945 birth cohort. Projection of rates in the future showed an increase in incidence in males until 2022 and a decrease thereafter. Among females, the incidence rate was predicted to increase gradually until reaching its maximum around 2027, and to remain stable thereafter.The occurrence of mesothelioma is closely linked to occupational exposure to asbestos in the 1960s and 1970s and due to the long latency period the incidence of mesothelioma is projected to increase until the 2020s.
Eur Respir J. 2012 Jan 26. [Epub ahead of print]
Mesothelioma incidence projections in South East England.
Riaz SP, Coupland VH, Lüchtenborg M, Peake MD, Møller H.
Source
Thames Cancer Registry, 1st Floor, Capital House, 42 Weston Street, London SE1 3QD.
Abstract
We estimated the past and future age-standardised incidence rates of mesothelioma by birth cohort and by period of diagnosis in South East England.We extracted data on patients diagnosed with mesothelioma (ICD-10 C45) between 1960 and 2009 from the Thames Cancer Registry. We calculated the age-standardised incidence rates using the European standard population. We used age-cohort and age-period modelling to estimate the age-specific incidence rates for the 1900 to 1950 birth cohorts and the 1935 to 2034 calendar periods.A much more pronounced increase in mesothelioma incidence between 1972 and 2007 was observed in males than in females. In both sexes, the incidence rates increased in successive generations up to the 1945 birth cohort. Projection of rates in the future showed an increase in incidence in males until 2022 and a decrease thereafter. Among females, the incidence rate was predicted to increase gradually until reaching its maximum around 2027, and to remain stable thereafter.The occurrence of mesothelioma is closely linked to occupational exposure to asbestos in the 1960s and 1970s and due to the long latency period the incidence of mesothelioma is projected to increase until the 2020s.
From Respiration: Mechanisms of pleurodesis
http://www.ncbi.nlm.nih.gov/pubmed/22286268
Respiration. 2012;83(2):91-8. Epub 2012 Jan 20.
Mechanisms of pleurodesis.
Rodriguez-Panadero F, Montes-Worboys A.
Source
Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, and CIBER Enfermedades Respiratorias, Sevilla, Spain.
Abstract
Pleurodesis aims to obliterate the pleural space by producing extensive adhesion of the visceral and parietal pleura, in order to control relapse of either pleural effusions (mostly malignant) or pneumothorax. A tight and complete apposition between the two pleural layers is a necessary condition to obtain a successful pleurodesis, but - besides this mechanical aspect - there are many biological mechanisms that appear to be common to most of the sclerosing agents currently used. Following intrapleural application of the sclerosing agent, diffuse inflammation, pleural coagulation-fibrinolysis imbalance (favoring the formation of fibrin adhesions), recruitment and subsequent proliferation of fibroblasts, and collagen production are findings in the pleural space. The pleural mesothelial lining is the primary target for the sclerosant and plays a pivotal role in the whole pleurodesis process, including the release of several mediators like interleukin-8, transforming growth factor-β and basic fibroblast growth factor. When the tumor burden is high, normal mesothelial cells are scarce, and consequently the response to the sclerosing agent is decreased, leading to failure of pleurodesis. Also, the type of tumor in the pleural cavity may also affect the outcome of pleurodesis (diffuse malignant mesothelioma and metastatic lung carcinomas have a poorer response). There is general agreement that talc obtains the best results, and there are also preliminary experimental studies suggesting that it can induce apoptosis in tumor cells and inhibit angiogenesis, thus contributing to a better control of the malignant pleural effusion. There is concern about complications (possibly associated with talc but other agents as well) related to systemic inflammation and possible activation of the coagulation cascade. In order to prevent extrapleural talc dissemination, large-particle talc is recommended. Although it could - to some degree - interfere with the mechanisms leading to pleurodesis and a carefully balanced clinical decision has therefore to be made, prophylactic treatment with subcutaneous heparin is recommended during hospitalization (immediately before and after the pleurodesis procedure).
Respiration. 2012;83(2):91-8. Epub 2012 Jan 20.
Mechanisms of pleurodesis.
Rodriguez-Panadero F, Montes-Worboys A.
Source
Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, and CIBER Enfermedades Respiratorias, Sevilla, Spain.
Abstract
Pleurodesis aims to obliterate the pleural space by producing extensive adhesion of the visceral and parietal pleura, in order to control relapse of either pleural effusions (mostly malignant) or pneumothorax. A tight and complete apposition between the two pleural layers is a necessary condition to obtain a successful pleurodesis, but - besides this mechanical aspect - there are many biological mechanisms that appear to be common to most of the sclerosing agents currently used. Following intrapleural application of the sclerosing agent, diffuse inflammation, pleural coagulation-fibrinolysis imbalance (favoring the formation of fibrin adhesions), recruitment and subsequent proliferation of fibroblasts, and collagen production are findings in the pleural space. The pleural mesothelial lining is the primary target for the sclerosant and plays a pivotal role in the whole pleurodesis process, including the release of several mediators like interleukin-8, transforming growth factor-β and basic fibroblast growth factor. When the tumor burden is high, normal mesothelial cells are scarce, and consequently the response to the sclerosing agent is decreased, leading to failure of pleurodesis. Also, the type of tumor in the pleural cavity may also affect the outcome of pleurodesis (diffuse malignant mesothelioma and metastatic lung carcinomas have a poorer response). There is general agreement that talc obtains the best results, and there are also preliminary experimental studies suggesting that it can induce apoptosis in tumor cells and inhibit angiogenesis, thus contributing to a better control of the malignant pleural effusion. There is concern about complications (possibly associated with talc but other agents as well) related to systemic inflammation and possible activation of the coagulation cascade. In order to prevent extrapleural talc dissemination, large-particle talc is recommended. Although it could - to some degree - interfere with the mechanisms leading to pleurodesis and a carefully balanced clinical decision has therefore to be made, prophylactic treatment with subcutaneous heparin is recommended during hospitalization (immediately before and after the pleurodesis procedure).
From Osaka Prefectural Med Ctr: Mesothelioma chemotherapy with and without pemetrexed
http://www.ncbi.nlm.nih.gov/pubmed/22287752
Anticancer Res. 2012 Feb;32(2):609-13.
A Retrospective Study of Chemotherapy with and without Pemetrexed in Malignant Pleural Mesothelioma.
Higashiguchi M, Suzuki H, Hirashima T, Kobayashi M, Goya S, Okamoto N, Matsuura Y, Tamiya M, Morishita N, Tsumori T, Kawase I.
Source
Department of Thoracic Malignancy, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, 3-7-1 Habikino Habikino-shi, Osaka, 583-8588 Japan. puer_aeternus_0308@goo.jp.
Abstract
BACKGROUND:
The current standard first-line chemotherapy for malignant pleural mesothelioma (MPM) is pemetrexed and cisplatin. However, other regimens, with or without a platinum agent, are reported to be effective in the treatment of MPM.
PATIENTS AND METHODS:
Patients who were diagnosed with MPM and treated with chemotherapy between January 1999 and June 2010 at the Osaka Prefectural Medical Center for Respiratory and Allergic Diseases were studied, and the outcomes of these patients were retrospectively analyzed in relation to therapy.
RESULTS:
In total, 48 patients with MPM (42 men and 6 women) treated with chemotherapy were included in the current analysis. The median survival time (MST) and one-year survival rate in the pemetrexed-containing group were 541 days and 63.2%, respectively. The MST and one-year survival rate in the non-pemetrexed group were 516 days and 66.7%, respectively. Overall survival did not differ significantly with respect to the pemetrexed-containing regimen.
CONCLUSION:
The superiority of pemetrexed-containing regimens is equivocal. Non-pemetrexed-containing regimens may be potent alternatives.
Anticancer Res. 2012 Feb;32(2):609-13.
A Retrospective Study of Chemotherapy with and without Pemetrexed in Malignant Pleural Mesothelioma.
Higashiguchi M, Suzuki H, Hirashima T, Kobayashi M, Goya S, Okamoto N, Matsuura Y, Tamiya M, Morishita N, Tsumori T, Kawase I.
Source
Department of Thoracic Malignancy, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, 3-7-1 Habikino Habikino-shi, Osaka, 583-8588 Japan. puer_aeternus_0308@goo.jp.
Abstract
BACKGROUND:
The current standard first-line chemotherapy for malignant pleural mesothelioma (MPM) is pemetrexed and cisplatin. However, other regimens, with or without a platinum agent, are reported to be effective in the treatment of MPM.
PATIENTS AND METHODS:
Patients who were diagnosed with MPM and treated with chemotherapy between January 1999 and June 2010 at the Osaka Prefectural Medical Center for Respiratory and Allergic Diseases were studied, and the outcomes of these patients were retrospectively analyzed in relation to therapy.
RESULTS:
In total, 48 patients with MPM (42 men and 6 women) treated with chemotherapy were included in the current analysis. The median survival time (MST) and one-year survival rate in the pemetrexed-containing group were 541 days and 63.2%, respectively. The MST and one-year survival rate in the non-pemetrexed group were 516 days and 66.7%, respectively. Overall survival did not differ significantly with respect to the pemetrexed-containing regimen.
CONCLUSION:
The superiority of pemetrexed-containing regimens is equivocal. Non-pemetrexed-containing regimens may be potent alternatives.
Novel targeted therapeutic strategies for treating mesothelioma
http://www.ncbi.nlm.nih.gov/pubmed/22289125
Br J Pharmacol. 2012 Jan 31. doi: 10.1111/j.1476-5381.2012.01873.x. [Epub ahead of print]
Preclinical studies identify novel targeted pharmacological strategies for treatment of human malignant pleural mesothelioma.
Favoni RE, Daga A, Malatesta P, Florio T.
Source
Department of Translational Oncology Research, Laboratory of Gene Transfer, National Cancer Institute, Department of Experimental Medicine, Department of Internal Medicine, Section of Pharmacology, University of Genoa, Largo Rosanna Benzi, 10 16132 - Genoa, ITALY; Center of Excellence for Biomedical Research, University of Genoa, Viale Benedetto XV, 2 16132 - Genoa, ITALY.
Abstract
The incidence of human malignant pleural mesothelioma (hMPM) is still increasing worldwide. hMPM prognosis is poor even if the median survival time has been slightly improved after the introduction of the up-to-date chemotherapy. Nevertheless, large phase II/III trials support the combination of platinum-derivatives and pemetrexed or raltitrexed, as preferred first-line schedule. Better understanding of the molecular machinery of hMPM will lead to the design and synthesis of novel compounds targeted against pathways identified as crucial for hMPM cell proliferation and spreading. Among them, several receptors tyrosine kinase show altered activity in subsets of hMPM. This observation suggests that these kinases might represent novel therapeutic targets in this chemotherapy-resistant disease. Over these foundations several promising studies are ongoing at preclinical level and novel molecules are currently under evaluation as well. Yet, established tumor cell lines, used for decades to investigate the efficacy of anticancer agents, although still the main source of drug efficacy studies, after long-term cultures tend to biologically diverge from the original tumor, limiting the predictive potential of in vivo efficacy. Cancer stem cells (CSCs), a subpopulation of malignant cells capable of self-renewal and multilineage differentiation, are believed to play an essential role in cancer initiation, growth, metastasization and relapse, being responsible of chemo- and radiotherapy refractoriness. According to current carcinogenesis theory, CSCs represent the tumor-initiating cell (TIC) fraction, the only clonogenic subpopulation able to originate a tumor mass. Consequently, the recently described isolation of TICs from hMPM, the proposed main pharmacological target for novel antitumoral drugs, may contribute to better dissect the biology and multidrug-resistance pathways controlling hMPM growth.
Br J Pharmacol. 2012 Jan 31. doi: 10.1111/j.1476-5381.2012.01873.x. [Epub ahead of print]
Preclinical studies identify novel targeted pharmacological strategies for treatment of human malignant pleural mesothelioma.
Favoni RE, Daga A, Malatesta P, Florio T.
Source
Department of Translational Oncology Research, Laboratory of Gene Transfer, National Cancer Institute, Department of Experimental Medicine, Department of Internal Medicine, Section of Pharmacology, University of Genoa, Largo Rosanna Benzi, 10 16132 - Genoa, ITALY; Center of Excellence for Biomedical Research, University of Genoa, Viale Benedetto XV, 2 16132 - Genoa, ITALY.
Abstract
The incidence of human malignant pleural mesothelioma (hMPM) is still increasing worldwide. hMPM prognosis is poor even if the median survival time has been slightly improved after the introduction of the up-to-date chemotherapy. Nevertheless, large phase II/III trials support the combination of platinum-derivatives and pemetrexed or raltitrexed, as preferred first-line schedule. Better understanding of the molecular machinery of hMPM will lead to the design and synthesis of novel compounds targeted against pathways identified as crucial for hMPM cell proliferation and spreading. Among them, several receptors tyrosine kinase show altered activity in subsets of hMPM. This observation suggests that these kinases might represent novel therapeutic targets in this chemotherapy-resistant disease. Over these foundations several promising studies are ongoing at preclinical level and novel molecules are currently under evaluation as well. Yet, established tumor cell lines, used for decades to investigate the efficacy of anticancer agents, although still the main source of drug efficacy studies, after long-term cultures tend to biologically diverge from the original tumor, limiting the predictive potential of in vivo efficacy. Cancer stem cells (CSCs), a subpopulation of malignant cells capable of self-renewal and multilineage differentiation, are believed to play an essential role in cancer initiation, growth, metastasization and relapse, being responsible of chemo- and radiotherapy refractoriness. According to current carcinogenesis theory, CSCs represent the tumor-initiating cell (TIC) fraction, the only clonogenic subpopulation able to originate a tumor mass. Consequently, the recently described isolation of TICs from hMPM, the proposed main pharmacological target for novel antitumoral drugs, may contribute to better dissect the biology and multidrug-resistance pathways controlling hMPM growth.
The role of regulatory T cells in mesothelioma
http://www.ncbi.nlm.nih.gov/pubmed/22302659
Cancer Microenviron. 2012 Feb 1. [Epub ahead of print]
The Role of Regulatory T Cells in Mesothelioma.
Ireland DJ, Kissick HT, Beilharz MW.
Source
School of Pathology and Laboratory Medicine (M502), Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia, demelza.ireland@uwa.edu.au.
Abstract
Malignant mesothelioma (MM) appears to be responsive to immunotherapy. The lack of complete tumour cure as a result of many immunotherapies tested to date suggests that the immune response to MM is complex and multi-parametric. Regulatory T (Treg) cells are prevalent within murine and human mesotheliomas with their removal shown to result in tumour growth inhibition and the release of anti-tumour effector T cells from immunosuppression. The targeting of immune checkpoints as treatments for various solid tumours has recently shown promise in clinical settings. In addition, synergy between chemotherapy and immunotherapy has been demonstrated for many cancers, including mesothelioma. Here we demonstrate Treg cells as critical mediators of the anti-tumour immune response to MM and potential targets for anti-tumour immunotherapy; though the timing and dosage of Treg cell manipulating immunotherapies need to be optimised.
Cancer Microenviron. 2012 Feb 1. [Epub ahead of print]
The Role of Regulatory T Cells in Mesothelioma.
Ireland DJ, Kissick HT, Beilharz MW.
Source
School of Pathology and Laboratory Medicine (M502), Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia, demelza.ireland@uwa.edu.au.
Abstract
Malignant mesothelioma (MM) appears to be responsive to immunotherapy. The lack of complete tumour cure as a result of many immunotherapies tested to date suggests that the immune response to MM is complex and multi-parametric. Regulatory T (Treg) cells are prevalent within murine and human mesotheliomas with their removal shown to result in tumour growth inhibition and the release of anti-tumour effector T cells from immunosuppression. The targeting of immune checkpoints as treatments for various solid tumours has recently shown promise in clinical settings. In addition, synergy between chemotherapy and immunotherapy has been demonstrated for many cancers, including mesothelioma. Here we demonstrate Treg cells as critical mediators of the anti-tumour immune response to MM and potential targets for anti-tumour immunotherapy; though the timing and dosage of Treg cell manipulating immunotherapies need to be optimised.
Pleural fluid cytologic yield and visceral pleural invasion in mesothelioma patients
http://www.ncbi.nlm.nih.gov/pubmed/22307010
J Thorac Oncol. 2012 Feb 2. [Epub ahead of print]
Pleural Fluid Cytological Yield and Visceral Pleural Invasion in Patients with Epithelioid Malignant Pleural Mesothelioma.
Pinelli V, Laroumagne S, Sakr L, Marchetti GP, Tassi GF, Astoul P.
Source
*Divisione di Pneumologia, Spedali Civili, Brescia, Italy; †Division of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonology, North Hospital, University of The Mediterranean, Marseille, France; and ‡Division of Pulmonary Diseases, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada.
Abstract
INTRODUCTION:
Malignant pleural mesothelioma (MPM) is an aggressive malignancy arising from mesothelial cells lining the pleura. Most commonly, it presents as a unilateral pleural effusion. MPM usually develops on the parietal pleural surface and later spreads to the visceral pleura. Visceral pleural involvement entails a more advanced disease stage and is therefore an important prognostic factor. Pleural fluid (PF) cytology is often the first diagnostic test, but the sensitivity in the literature varies from 4 to 77%. However, no data are available for the diagnostic yield of cytological PF analysis with regard to the visceral pleural involvement. The aim of this study is to assess whether PF cytological yield is related to the extent and pattern of visceral pleural invasion, as assessed by thoracoscopy.
METHODS:
Medical records of all patients who underwent thoracoscopy for suspicion of malignant pleural effusion from two hospitals were reviewed. Patients were selected if they initially underwent a diagnostic thoracentesis before thoracoscopy, if visceral pleural appearance during thoracoscopy was clearly documented, and MPM confirmed on pleural tissue biopsy.
RESULTS:
Seventy-five patients were selected. Forty-five patients had a positive PF cytology on thoracentesis, while 30 had a negative PF cytology. Thoracoscopy showed parietal pleural invasion in all subjects. Interestingly, 82% of patients with positive PF cytology on thoracentesis had visceral pleural involvement, whereas only 30% of those with negative PF cytology had visceral pleural invasion. The pattern of visceral pleural invasion consisted of pleural masses, nodules, or pleural thickening. A multivariate regression identified visceral pleural invasion (p < 0.001) as the only independent factor predicting the positivity of cytology on pleural effusion.
CONCLUSION:
In epithelioid MPM, PF cytological yield was significantly higher in patients with visceral pleural invasion assessed by thoracoscopy. Positive PF cytology is associated with a more advanced disease.
J Thorac Oncol. 2012 Feb 2. [Epub ahead of print]
Pleural Fluid Cytological Yield and Visceral Pleural Invasion in Patients with Epithelioid Malignant Pleural Mesothelioma.
Pinelli V, Laroumagne S, Sakr L, Marchetti GP, Tassi GF, Astoul P.
Source
*Divisione di Pneumologia, Spedali Civili, Brescia, Italy; †Division of Thoracic Oncology, Pleural Diseases, and Interventional Pulmonology, North Hospital, University of The Mediterranean, Marseille, France; and ‡Division of Pulmonary Diseases, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada.
Abstract
INTRODUCTION:
Malignant pleural mesothelioma (MPM) is an aggressive malignancy arising from mesothelial cells lining the pleura. Most commonly, it presents as a unilateral pleural effusion. MPM usually develops on the parietal pleural surface and later spreads to the visceral pleura. Visceral pleural involvement entails a more advanced disease stage and is therefore an important prognostic factor. Pleural fluid (PF) cytology is often the first diagnostic test, but the sensitivity in the literature varies from 4 to 77%. However, no data are available for the diagnostic yield of cytological PF analysis with regard to the visceral pleural involvement. The aim of this study is to assess whether PF cytological yield is related to the extent and pattern of visceral pleural invasion, as assessed by thoracoscopy.
METHODS:
Medical records of all patients who underwent thoracoscopy for suspicion of malignant pleural effusion from two hospitals were reviewed. Patients were selected if they initially underwent a diagnostic thoracentesis before thoracoscopy, if visceral pleural appearance during thoracoscopy was clearly documented, and MPM confirmed on pleural tissue biopsy.
RESULTS:
Seventy-five patients were selected. Forty-five patients had a positive PF cytology on thoracentesis, while 30 had a negative PF cytology. Thoracoscopy showed parietal pleural invasion in all subjects. Interestingly, 82% of patients with positive PF cytology on thoracentesis had visceral pleural involvement, whereas only 30% of those with negative PF cytology had visceral pleural invasion. The pattern of visceral pleural invasion consisted of pleural masses, nodules, or pleural thickening. A multivariate regression identified visceral pleural invasion (p < 0.001) as the only independent factor predicting the positivity of cytology on pleural effusion.
CONCLUSION:
In epithelioid MPM, PF cytological yield was significantly higher in patients with visceral pleural invasion assessed by thoracoscopy. Positive PF cytology is associated with a more advanced disease.
From J Thoracic Oncology: Inflammation-based prognostic indices in pleural mesothelioma
http://www.ncbi.nlm.nih.gov/pubmed/22307011
J Thorac Oncol. 2012 Feb 2. [Epub ahead of print]
Inflammation-Based Prognostic Indices in Malignant Pleural Mesothelioma.
Pinato DJ, Mauri FA, Ramakrishnan R, Wahab L, Lloyd T, Sharma R.
Source
*Department of Investigative Sciences, Imperial College London, Hammersmith Campus, London, United Kingdom; †Department of Clinical and Experimental Medicine, Universitá degli Studi del Piemonte Orientale "A. Avogadro," Via Solaroli, Novara, Italy; ‡Department of Histopathology, Imperial College London, Hammersmith Campus, London, United Kingdom; and §Department of Histopathology, Imperial College London, St. Mary's Campus, London, United Kingdom.
Abstract
INTRODUCTION:
Chronic inflammation plays a key role in the pathogenesis of malignant pleural mesothelioma (MPM) as a result of asbestos exposure. Biomarkers of systemic inflammation have been shown to predict the natural history of MPM; however, this observation lacks independent validation. Our aim was to compare the prognostic performance of three inflammation-based biomarkers in predicting overall survival (OS) in MPM.
METHODS:
In patients with histologically proven MPM, the inflammation-based prognostic scores modified Glasgow Prognostic Score (mGPS), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio were studied and compared with the European Organization for the Research and Treatment of Cancer Prognostic Score (EPS) and other known potential prognostic factors such as gender, histologic subtype, Eastern Cooperative Oncology Group performance status, and baseline blood parameters.
RESULTS:
A total of 171 MPM patients presenting to Imperial College NHS Trust were studied. In univariate analyses, the following parameters were predictors of OS: female gender (p = 0.03), epithelioid histology (p = 0.03), normal C-reactive protein (p = 0.03), baseline white blood cell count <8.3 × 10/liter (p = 0.04), EPS (p = 0.003), mGPS (p < 0.001), NLR (p = 0.006), and platelet-to-lymphocyte ratio (p = 0.03). Multivariate survival analysis confirmed the mGPS (hazard ratio = 2.6; p < 0.001) and NLR (hazard ratio = 2.0; p = 0.008), but not the EPS, as independent predictors of OS. Tissue expression of Ki-67 (p < 0.001) and vascular endothelial growth factor (p < 0.001) was higher in a subgroup of patients with high-risk inflammatory scores.
CONCLUSIONS:
The mGPS and NLR are externally validated prognostic indices in patients with MPM and correlate with sustained neoangiogenesis and increased proliferative index.
J Thorac Oncol. 2012 Feb 2. [Epub ahead of print]
Inflammation-Based Prognostic Indices in Malignant Pleural Mesothelioma.
Pinato DJ, Mauri FA, Ramakrishnan R, Wahab L, Lloyd T, Sharma R.
Source
*Department of Investigative Sciences, Imperial College London, Hammersmith Campus, London, United Kingdom; †Department of Clinical and Experimental Medicine, Universitá degli Studi del Piemonte Orientale "A. Avogadro," Via Solaroli, Novara, Italy; ‡Department of Histopathology, Imperial College London, Hammersmith Campus, London, United Kingdom; and §Department of Histopathology, Imperial College London, St. Mary's Campus, London, United Kingdom.
Abstract
INTRODUCTION:
Chronic inflammation plays a key role in the pathogenesis of malignant pleural mesothelioma (MPM) as a result of asbestos exposure. Biomarkers of systemic inflammation have been shown to predict the natural history of MPM; however, this observation lacks independent validation. Our aim was to compare the prognostic performance of three inflammation-based biomarkers in predicting overall survival (OS) in MPM.
METHODS:
In patients with histologically proven MPM, the inflammation-based prognostic scores modified Glasgow Prognostic Score (mGPS), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio were studied and compared with the European Organization for the Research and Treatment of Cancer Prognostic Score (EPS) and other known potential prognostic factors such as gender, histologic subtype, Eastern Cooperative Oncology Group performance status, and baseline blood parameters.
RESULTS:
A total of 171 MPM patients presenting to Imperial College NHS Trust were studied. In univariate analyses, the following parameters were predictors of OS: female gender (p = 0.03), epithelioid histology (p = 0.03), normal C-reactive protein (p = 0.03), baseline white blood cell count <8.3 × 10/liter (p = 0.04), EPS (p = 0.003), mGPS (p < 0.001), NLR (p = 0.006), and platelet-to-lymphocyte ratio (p = 0.03). Multivariate survival analysis confirmed the mGPS (hazard ratio = 2.6; p < 0.001) and NLR (hazard ratio = 2.0; p = 0.008), but not the EPS, as independent predictors of OS. Tissue expression of Ki-67 (p < 0.001) and vascular endothelial growth factor (p < 0.001) was higher in a subgroup of patients with high-risk inflammatory scores.
CONCLUSIONS:
The mGPS and NLR are externally validated prognostic indices in patients with MPM and correlate with sustained neoangiogenesis and increased proliferative index.
Not surprising given the pathophysiology. "stopping exposure does not materially modify the subsequent risk of mesothelioma"
http://www.ncbi.nlm.nih.gov/pubmed/22314851
Eur J Cancer Prev. 2012 Feb 5. [Epub ahead of print]
Role of stopping exposure and recent exposure to asbestos in the risk of mesothelioma.
La Vecchia C, Boffetta P.
Source
aDepartment of Epidemiology, 'Mario Negri' Institute for Pharmacological Research bDepartment of Occupational Health, University of Milan, Milan, Italy cInternational Prevention Research Institute, Lyon, France dThe Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York, USA.
Abstract
The model of asbestos-related mesothelioma implies that the time since first exposure (latency) is the key determinant of subsequent risk. The role of recent exposure or stopping asbestos exposure, if any, is, however, open to discussion. A literature review was conducted to the end of 2010. In a cohort of 1966 Italian textile workers, the standardized mortality ratio, on the basis of 68 deaths from mesothelioma, was 6627 for workers employed only under the age of 30 years, 8019 for those employed both under the age of 30 years and at the age of 30-39 years, and 5891 for those employed both under the age of 30 years and at the age of 40 years or more. In a cohort of Italian asbestos cement workers, including 135 deaths from pleural cancer, compared with workers who had stopped exposure for 3-15 years, the relative risk (RR) was similar for those still employed (RR=0.67) and for those who had stopped for 30 years or more (RR=0.65). In a British case-control study, including 622 cases of mesothelioma and 1420 population controls, the RR substantially increased with increasing duration of exposure under the age of 30 years, but not with exposure at the age of more than 30 years. In the Great Britain Asbestos Workers Survey, including 649 deaths from mesothelioma compared with workers who were still employed and or had stopped for less than 10 years, the multivariate RRs were 0.90 10-20 years after stopping exposure and 0.99 both 20-30 and more than 30 years after stopping. There is consistent evidence showing that, for workers exposed in the distant past, the risk of mesothelioma is not appreciably modified by subsequent exposures, and that stopping exposure does not materially modify the subsequent risk of mesothelioma.
Eur J Cancer Prev. 2012 Feb 5. [Epub ahead of print]
Role of stopping exposure and recent exposure to asbestos in the risk of mesothelioma.
La Vecchia C, Boffetta P.
Source
aDepartment of Epidemiology, 'Mario Negri' Institute for Pharmacological Research bDepartment of Occupational Health, University of Milan, Milan, Italy cInternational Prevention Research Institute, Lyon, France dThe Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York, USA.
Abstract
The model of asbestos-related mesothelioma implies that the time since first exposure (latency) is the key determinant of subsequent risk. The role of recent exposure or stopping asbestos exposure, if any, is, however, open to discussion. A literature review was conducted to the end of 2010. In a cohort of 1966 Italian textile workers, the standardized mortality ratio, on the basis of 68 deaths from mesothelioma, was 6627 for workers employed only under the age of 30 years, 8019 for those employed both under the age of 30 years and at the age of 30-39 years, and 5891 for those employed both under the age of 30 years and at the age of 40 years or more. In a cohort of Italian asbestos cement workers, including 135 deaths from pleural cancer, compared with workers who had stopped exposure for 3-15 years, the relative risk (RR) was similar for those still employed (RR=0.67) and for those who had stopped for 30 years or more (RR=0.65). In a British case-control study, including 622 cases of mesothelioma and 1420 population controls, the RR substantially increased with increasing duration of exposure under the age of 30 years, but not with exposure at the age of more than 30 years. In the Great Britain Asbestos Workers Survey, including 649 deaths from mesothelioma compared with workers who were still employed and or had stopped for less than 10 years, the multivariate RRs were 0.90 10-20 years after stopping exposure and 0.99 both 20-30 and more than 30 years after stopping. There is consistent evidence showing that, for workers exposed in the distant past, the risk of mesothelioma is not appreciably modified by subsequent exposures, and that stopping exposure does not materially modify the subsequent risk of mesothelioma.
From British J Cancer: Mesotheliomas in Western Australia-50-year follow-up
http://www.ncbi.nlm.nih.gov/pubmed/22315054
Br J Cancer. 2012 Feb 7. doi: 10.1038/bjc.2012.23. [Epub ahead of print]
Malignant mesotheliomas in former miners and millers of crocidolite at Wittenoom (Western Australia) after more than 50 years follow-up.
Berry G, Reid A, Aboagye-Sarfo P, de Klerk NH, Olsen NJ, Merler E, Franklin P, Musk AW.
Source
Sydney School of Public Health, University of Sydney, Sydney, New South Wales 2006, Australia.
Abstract
Background:
To report the number of malignant pleural and peritoneal mesotheliomas that have occurred in former Wittenoom crocidolite workers to the end of 2008, to compare this with earlier predictions, and to relate the mesothelioma rate to amount of exposure.
Methods:
A group of 6489 men and 419 women who had worked for the company operating the former Wittenoom crocidolite mine and mill at some time between 1943 and 1966 have been followed up throughout Australia and Italy to the end of 2008.
Results:
The cumulative number of mesotheliomas up to 2008 was 316 in men (268 pleural, 48 peritoneal) and 13 (all pleural) in women. There had been 302 deaths with mesothelioma in men and 13 in women, which was almost 10% of all known deaths. Mesothelioma rate, both pleural and peritoneal, increased with time since first exposure and appeared to reach a plateau after about 40 to 50 years. The mesothelioma rate increased with amount of exposure and the peritoneal mesotheliomas occurred preferentially in the highest exposure group, 37% compared with 15% overall.
Conclusion:
By the end of 2008, the number of mesothelioma deaths had reached 4.7% for all the male workers and 3.1% for the females. Over the past 8 years the numbers were higher than expected. It is predicted that about another 60 to 70 deaths with mesothelioma may occur in men by 2020
Br J Cancer. 2012 Feb 7. doi: 10.1038/bjc.2012.23. [Epub ahead of print]
Malignant mesotheliomas in former miners and millers of crocidolite at Wittenoom (Western Australia) after more than 50 years follow-up.
Berry G, Reid A, Aboagye-Sarfo P, de Klerk NH, Olsen NJ, Merler E, Franklin P, Musk AW.
Source
Sydney School of Public Health, University of Sydney, Sydney, New South Wales 2006, Australia.
Abstract
Background:
To report the number of malignant pleural and peritoneal mesotheliomas that have occurred in former Wittenoom crocidolite workers to the end of 2008, to compare this with earlier predictions, and to relate the mesothelioma rate to amount of exposure.
Methods:
A group of 6489 men and 419 women who had worked for the company operating the former Wittenoom crocidolite mine and mill at some time between 1943 and 1966 have been followed up throughout Australia and Italy to the end of 2008.
Results:
The cumulative number of mesotheliomas up to 2008 was 316 in men (268 pleural, 48 peritoneal) and 13 (all pleural) in women. There had been 302 deaths with mesothelioma in men and 13 in women, which was almost 10% of all known deaths. Mesothelioma rate, both pleural and peritoneal, increased with time since first exposure and appeared to reach a plateau after about 40 to 50 years. The mesothelioma rate increased with amount of exposure and the peritoneal mesotheliomas occurred preferentially in the highest exposure group, 37% compared with 15% overall.
Conclusion:
By the end of 2008, the number of mesothelioma deaths had reached 4.7% for all the male workers and 3.1% for the females. Over the past 8 years the numbers were higher than expected. It is predicted that about another 60 to 70 deaths with mesothelioma may occur in men by 2020
From Paul Sugarbaker: Parietal peritonectomy for patients with peritoneal surface malignancies
http://www.ncbi.nlm.nih.gov/pubmed/22322950
Ann Surg Oncol. 2012 Feb 10. [Epub ahead of print]
Parietal Peritonectomy.
Sugarbaker PH.
Source
Washington Cancer Institute, Washington Hospital Center, Washington, DC, USA, Paul.Sugarbaker@medstar.net.
Abstract
Parietal peritonectomy is an initial part of cytoreductive surgery in patients with peritoneal surface malignancy. After this dissection, the necessary visceral resections, other peritonectomy procedures, and perioperative hyperthermic chemotherapy are administered. The parietal peritoneum is an immobile portion of the abdominal and pelvic surface area that is often involved by cancer implants in patients with carcinomatosis or peritoneal mesothelioma. The dependent peritoneal surfaces, such as the right retrohepatic space, paracolic sulcus, and pelvis, are involved as a result of gravitational forces. The undersurfaces of the diaphragm and omentums are involved because of major peritoneal fluid resorption at these anatomic sites. Before the parietal peritonectomy is initiated, a peritoneal window is created to digitally and visually inspect the undersurface of the anterior abdominal wall, small bowel, and small bowel mesentery. This inspection is frequently repeated so that parietal peritoneum is removed only where there is visible evidence of cancer implants. Electrosurgery is used as a dissection tool. The dissection proceeds in a centripetal fashion starting at the edges of the large midline abdominal incision and proceeding to the attachments of the peritoneum to the viscera. Initially, exposure is maintained with traction sutures from the skin edge to the fixed retractor. As the dissection deepens, a self-retaining retractor is positioned. Generally, the parietal peritonectomy takes approximately 2½ h and does not require blood replacement. After the parietal peritonectomy, additional cytoreductive surgical procedures and then perioperative chemotherapy are performed.
Ann Surg Oncol. 2012 Feb 10. [Epub ahead of print]
Parietal Peritonectomy.
Sugarbaker PH.
Source
Washington Cancer Institute, Washington Hospital Center, Washington, DC, USA, Paul.Sugarbaker@medstar.net.
Abstract
Parietal peritonectomy is an initial part of cytoreductive surgery in patients with peritoneal surface malignancy. After this dissection, the necessary visceral resections, other peritonectomy procedures, and perioperative hyperthermic chemotherapy are administered. The parietal peritoneum is an immobile portion of the abdominal and pelvic surface area that is often involved by cancer implants in patients with carcinomatosis or peritoneal mesothelioma. The dependent peritoneal surfaces, such as the right retrohepatic space, paracolic sulcus, and pelvis, are involved as a result of gravitational forces. The undersurfaces of the diaphragm and omentums are involved because of major peritoneal fluid resorption at these anatomic sites. Before the parietal peritonectomy is initiated, a peritoneal window is created to digitally and visually inspect the undersurface of the anterior abdominal wall, small bowel, and small bowel mesentery. This inspection is frequently repeated so that parietal peritoneum is removed only where there is visible evidence of cancer implants. Electrosurgery is used as a dissection tool. The dissection proceeds in a centripetal fashion starting at the edges of the large midline abdominal incision and proceeding to the attachments of the peritoneum to the viscera. Initially, exposure is maintained with traction sutures from the skin edge to the fixed retractor. As the dissection deepens, a self-retaining retractor is positioned. Generally, the parietal peritonectomy takes approximately 2½ h and does not require blood replacement. After the parietal peritonectomy, additional cytoreductive surgical procedures and then perioperative chemotherapy are performed.
Asbestosis in Louisiana
http://www.ncbi.nlm.nih.gov/pubmed/22324095
J La State Med Soc. 2011 Nov-Dec;163(6):336-41.
Asbestosis in Louisiana: a descriptive review and demographic analysis of hospitalizations for abestosis, 1999-2009.
Davis C, Vijaykumar J, Lackovic M, Diaz JH.
Source
Louisiana Department of Health and Hospitals, Office of Public Health, Section of Environmental Epidemiology and Toxicology, USA.
Abstract
Asbestosis is a debilitating, chronic, lung disease with no known treatment and most commonly occurs among workers in certain occupational settings. As a condition highly associated with occupational exposure, its incidence has been affected by changes in industry standards. In particular, the bans on both production and new uses of asbestos fibers put in place during the past 20 to 30 years have significantly reduced occupational exposures. Despite these restrictions, asbestos can still be found in many products. Louisiana has more facilities that produce, process, or use asbestos than any other state in the US. Health outcomes associated with asbestos exposure include asbestosis, mesothelioma, and lung cancer. To evaluate the impact of asbestos exposure on Louisiana residents, Louisiana Hospital Inpatient Discharge Data (LAHIDD) from 1999-2009 was analyzed. Results indicate that asbestosis hospitalizations have remained steady over the 11-year period with approximately 295 cases per year. White males have the highest rates, and cases are clustered geographically. Overall, Louisiana's rate is significantly greater than the US rate (p < 0.0001).
J La State Med Soc. 2011 Nov-Dec;163(6):336-41.
Asbestosis in Louisiana: a descriptive review and demographic analysis of hospitalizations for abestosis, 1999-2009.
Davis C, Vijaykumar J, Lackovic M, Diaz JH.
Source
Louisiana Department of Health and Hospitals, Office of Public Health, Section of Environmental Epidemiology and Toxicology, USA.
Abstract
Asbestosis is a debilitating, chronic, lung disease with no known treatment and most commonly occurs among workers in certain occupational settings. As a condition highly associated with occupational exposure, its incidence has been affected by changes in industry standards. In particular, the bans on both production and new uses of asbestos fibers put in place during the past 20 to 30 years have significantly reduced occupational exposures. Despite these restrictions, asbestos can still be found in many products. Louisiana has more facilities that produce, process, or use asbestos than any other state in the US. Health outcomes associated with asbestos exposure include asbestosis, mesothelioma, and lung cancer. To evaluate the impact of asbestos exposure on Louisiana residents, Louisiana Hospital Inpatient Discharge Data (LAHIDD) from 1999-2009 was analyzed. Results indicate that asbestosis hospitalizations have remained steady over the 11-year period with approximately 295 cases per year. White males have the highest rates, and cases are clustered geographically. Overall, Louisiana's rate is significantly greater than the US rate (p < 0.0001).
Tuesday, February 14, 2012
From Victoria U-Melbourne: Nursing and casemix-based activity funding
http://www.ncbi.nlm.nih.gov/pubmed/22257324
Int J Nurs Pract. 2012 Feb;18(1):2-6. doi: 10.1111/j.1440-172X.2011.01992.x.
Status of costing hospital nursing work within Australian casemix activity-based funding policy.
Heslop L.
Source
Associate Professor, School of Nursing and Midwifery, Centre for Applied Informatics, Victoria University, Melbourne, Victoria, Australia.
Abstract
Status of costing hospital nursing work within Australian casemix activity-based funding policy Australia has a long history of patient level costing initiated when casemix funding was implemented in several states in the early 1990s. Australia includes, to some extent, hospital payment based on nursing intensity adopted within casemix funding policy and the Diagnostic Related Group system. Costing of hospital nursing services in Australia has not changed significantly in the last few decades despite widespread introduction of casemix funding policy at the state level. Recent Commonwealth of Australia National Health Reform presents change to the management of the delivery of health care including health-care costing. There is agreement for all Australian jurisdictions to progress to casemix-based activity funding. Within this context, nurse costing infrastructure presents contemporary issues and challenges. An assessment is made of the progress of costing nursing services within casemix funding models in Australian hospitals. Valid and reliable Australian-refined nursing service weights might overcome present cost deficiencies and limitations.
Int J Nurs Pract. 2012 Feb;18(1):2-6. doi: 10.1111/j.1440-172X.2011.01992.x.
Status of costing hospital nursing work within Australian casemix activity-based funding policy.
Heslop L.
Source
Associate Professor, School of Nursing and Midwifery, Centre for Applied Informatics, Victoria University, Melbourne, Victoria, Australia.
Abstract
Status of costing hospital nursing work within Australian casemix activity-based funding policy Australia has a long history of patient level costing initiated when casemix funding was implemented in several states in the early 1990s. Australia includes, to some extent, hospital payment based on nursing intensity adopted within casemix funding policy and the Diagnostic Related Group system. Costing of hospital nursing services in Australia has not changed significantly in the last few decades despite widespread introduction of casemix funding policy at the state level. Recent Commonwealth of Australia National Health Reform presents change to the management of the delivery of health care including health-care costing. There is agreement for all Australian jurisdictions to progress to casemix-based activity funding. Within this context, nurse costing infrastructure presents contemporary issues and challenges. An assessment is made of the progress of costing nursing services within casemix funding models in Australian hospitals. Valid and reliable Australian-refined nursing service weights might overcome present cost deficiencies and limitations.
Health care's elephant in the living room.
http://www.ncbi.nlm.nih.gov/pubmed/22272530
Nurs Stand. 2012 Jan 4-10;26(18):1.
Without the resources, quality will suffer.
Scott G.
Nurs Stand. 2012 Jan 4-10;26(18):1.
Without the resources, quality will suffer.
Scott G.
From Rutgers: PPACA coverage of young adults. (Not discussed-is this creeping infantilization of society?)
http://www.ncbi.nlm.nih.gov/pubmed/22273776
J Health Polit Policy Law. 2012 Feb;37(1):99-128.
Expanding dependent coverage for young adults: lessons from state initiatives.
Cantor JC, Belloff D, Monheit AC, Delia D, Koller M.
Source
Rutgers University.
Abstract
The Patient Protection and Affordable Care Act (ACA) requires that adults up to age twenty-six be permitted to enroll as dependents on their parents' health plans. This article examines the experiences of states that enacted dependent expansion laws. Drawing on public information from thirty-one enacting states and case studies of four diverse reform states, it derives lessons that are pertinent to the implementation of this ACA provision. Dependent coverage laws vary across the states, but most impose residency, marital status, and other restrictions. The federal Employee Retirement Income Security Act further limits the reach of state laws. Eligibility for expanded coverage under the ACA is much broader. Rules in some states requiring or allowing separate premiums for adult dependents may also discourage enrollment compared with rules in other states (and the ACA), where these costs must be factored into family premiums. Business opposition in some states led to more restrictive regulations, especially for how premiums are charged, which in turn raised greater implementation challenges. Case study states did not report substantial young adult dependent coverage take-up, but early enrollment experience under ACA appears to be more positive. Long-term questions remain about the implications of this policy for risk pooling and the distribution of premium costs.
J Health Polit Policy Law. 2012 Feb;37(1):99-128.
Expanding dependent coverage for young adults: lessons from state initiatives.
Cantor JC, Belloff D, Monheit AC, Delia D, Koller M.
Source
Rutgers University.
Abstract
The Patient Protection and Affordable Care Act (ACA) requires that adults up to age twenty-six be permitted to enroll as dependents on their parents' health plans. This article examines the experiences of states that enacted dependent expansion laws. Drawing on public information from thirty-one enacting states and case studies of four diverse reform states, it derives lessons that are pertinent to the implementation of this ACA provision. Dependent coverage laws vary across the states, but most impose residency, marital status, and other restrictions. The federal Employee Retirement Income Security Act further limits the reach of state laws. Eligibility for expanded coverage under the ACA is much broader. Rules in some states requiring or allowing separate premiums for adult dependents may also discourage enrollment compared with rules in other states (and the ACA), where these costs must be factored into family premiums. Business opposition in some states led to more restrictive regulations, especially for how premiums are charged, which in turn raised greater implementation challenges. Case study states did not report substantial young adult dependent coverage take-up, but early enrollment experience under ACA appears to be more positive. Long-term questions remain about the implications of this policy for risk pooling and the distribution of premium costs.
Patient empowerment
http://www.ncbi.nlm.nih.gov/pubmed/22278387
Intern Emerg Med. 2012 Jan 26. [Epub ahead of print]
Patient empowerment as a component of health system reforms: rights, benefits and vested interests.
Colombo C, Moja L, Gonzalez-Lorenzo M, Liberati A, Mosconi P.
Source
Laboratory for Medical Research and Consumer Involvement, Mario Negri Institute for Pharmacological Research, Milan, Italy.
Abstract
Different strategies have been developed across countries to foster citizens' and patients' involvement, from health policies to patients' active participation in decisions regarding their health. The spectrum varies from systems where patients lead the reform of health care services, to others where a paternalistic approach still limits patients' autonomy in decision-making. This paper describes: (1) different interventions for involving patients; (2) experiences to promote consumer evidence-based advocacy; and (3) barriers to consumer involvement in health system reforms, including vested interests in patients' associations. Citizens' involvement in health systems can vary substantially, but is gaining increasing weight.
Intern Emerg Med. 2012 Jan 26. [Epub ahead of print]
Patient empowerment as a component of health system reforms: rights, benefits and vested interests.
Colombo C, Moja L, Gonzalez-Lorenzo M, Liberati A, Mosconi P.
Source
Laboratory for Medical Research and Consumer Involvement, Mario Negri Institute for Pharmacological Research, Milan, Italy.
Abstract
Different strategies have been developed across countries to foster citizens' and patients' involvement, from health policies to patients' active participation in decisions regarding their health. The spectrum varies from systems where patients lead the reform of health care services, to others where a paternalistic approach still limits patients' autonomy in decision-making. This paper describes: (1) different interventions for involving patients; (2) experiences to promote consumer evidence-based advocacy; and (3) barriers to consumer involvement in health system reforms, including vested interests in patients' associations. Citizens' involvement in health systems can vary substantially, but is gaining increasing weight.
From NEJM: Can ACOs work?
http://www.ncbi.nlm.nih.gov/pubmed/22296073
N Engl J Med. 2012 Feb 2;366(5):393-5.
Keeping score under a global payment system.
Landon BE.
Source
Department of Health Care Policy, Harvard Medical School, and Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, USA.
"Conceptually, global payment represents an important opportunity for changing the perverse incentives inherent in our current fee-for-service system. To be successful, however, ACOs must pass these incentives along to their member physicians, who continue to be responsible for most utilization decisions. Although organizations can implement various managerial strategies to influence physicians' decision making (e.g., radiology decision support and prior authorization), ACOs are unlikely to reduce the rate of increase in health care spending without some essential changes in the behavior of member physicians — and therein lies the rub. The fundamental questions become how ACOs will choose to divide their global budgets and how their physicians and other service providers will be reimbursed. Thus, this system for determining who has earned what portion of payments — keeping score — is likely to be crucially important to the success of these new models of care."
N Engl J Med. 2012 Feb 2;366(5):393-5.
Keeping score under a global payment system.
Landon BE.
Source
Department of Health Care Policy, Harvard Medical School, and Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, USA.
"Conceptually, global payment represents an important opportunity for changing the perverse incentives inherent in our current fee-for-service system. To be successful, however, ACOs must pass these incentives along to their member physicians, who continue to be responsible for most utilization decisions. Although organizations can implement various managerial strategies to influence physicians' decision making (e.g., radiology decision support and prior authorization), ACOs are unlikely to reduce the rate of increase in health care spending without some essential changes in the behavior of member physicians — and therein lies the rub. The fundamental questions become how ACOs will choose to divide their global budgets and how their physicians and other service providers will be reimbursed. Thus, this system for determining who has earned what portion of payments — keeping score — is likely to be crucially important to the success of these new models of care."
From NEJM: Medicine and public health
http://www.ncbi.nlm.nih.gov/pubmed/22296074
N Engl J Med. 2012 Feb 2;366(5):395-7.
Opportunity in austerity--a common agenda for medicine and public health.
Stine NW, Chokshi DA.
Source
Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
"This seemingly imbalanced approach to health investment reflects a long-standing schism between medicine and public health, which remain professionally and institutionally distinct despite past calls for a closer bond.3 Ideally, population health would benefit from the integrated, complementary activities of a cooperative health sector. Often, however, the predominant interaction between a clinic or hospital and the local public health department is mandatory reporting of communicable diseases. Meanwhile, physicians and health care systems seeking to promote population health generally do so at their own expense, which leads to missed opportunities for both collaboration across health disciplines and potential cost savings."
N Engl J Med. 2012 Feb 2;366(5):395-7.
Opportunity in austerity--a common agenda for medicine and public health.
Stine NW, Chokshi DA.
Source
Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
"This seemingly imbalanced approach to health investment reflects a long-standing schism between medicine and public health, which remain professionally and institutionally distinct despite past calls for a closer bond.3 Ideally, population health would benefit from the integrated, complementary activities of a cooperative health sector. Often, however, the predominant interaction between a clinic or hospital and the local public health department is mandatory reporting of communicable diseases. Meanwhile, physicians and health care systems seeking to promote population health generally do so at their own expense, which leads to missed opportunities for both collaboration across health disciplines and potential cost savings."
Health care in Latin America: the quest for equity
http://www.ncbi.nlm.nih.gov/pubmed/22296659
Int J Equity Health. 2012 Feb 2;11(1):6. [Epub ahead of print]
The quest for equity in Latin America: a comparative analysis of the health care reforms in Brazil and Colombia.
Esteves RJ.
ABSTRACT:
INTRODUCTION:
Brazil and Colombia have pursued extensive reforms of their health care systems in the last couple of decades. The purported goals of such reforms were to improve access, increase efficiency and reduce health inequities. Notwithstanding their common goals, each country sought a very different pathway to achieve them. While Brazil attempted to reestablish a greater level of State control through a public national health system, Colombia embraced market competition under an employer-based social insurance scheme. This work thus aims to shed some light onto why they pursued divergent strategies and what that has meant in terms of health outcomes.
METHODS:
A critical review of the literature concerning equity frameworks, as well as the health care reforms in Brazil and Colombia was conducted. Then, the shortfall inequality values of crude mortality rate, infant mortality rate, under-five mortality rate, and life expectancy for the period 1960-2005 were calculated for both countries. Subsequently, bivariate and multivariate linear regression analyses were performed and controlled for possibly confounding factors.
RESULTS:
When controlling for the underlying historical time trend, both countries appear to have experienced a deceleration of the pace of improvements in the years following the reform, for all the variables analyzed. In the case of Colombia, some of the previous gains in under-five mortality rate and crude mortality rate were, in fact, reversed.
CONCLUSIONS:
Neither reform seems to have had a decisive positive impact on the health outcomes analyzed for the defined time period of this research. This, in turn, may be a consequence of both internal characteristics of the respective reforms and external factors beyond the direct control of health reformers. Among the internal characteristics: underfunding, unbridled decentralization and inequitable access to care seem to have been the main constraints. Conversely, international economic adversities, high levels of rural and urban violence, along with entrenched income inequalities seem to have accounted for the highest burden among external factors.
Int J Equity Health. 2012 Feb 2;11(1):6. [Epub ahead of print]
The quest for equity in Latin America: a comparative analysis of the health care reforms in Brazil and Colombia.
Esteves RJ.
ABSTRACT:
INTRODUCTION:
Brazil and Colombia have pursued extensive reforms of their health care systems in the last couple of decades. The purported goals of such reforms were to improve access, increase efficiency and reduce health inequities. Notwithstanding their common goals, each country sought a very different pathway to achieve them. While Brazil attempted to reestablish a greater level of State control through a public national health system, Colombia embraced market competition under an employer-based social insurance scheme. This work thus aims to shed some light onto why they pursued divergent strategies and what that has meant in terms of health outcomes.
METHODS:
A critical review of the literature concerning equity frameworks, as well as the health care reforms in Brazil and Colombia was conducted. Then, the shortfall inequality values of crude mortality rate, infant mortality rate, under-five mortality rate, and life expectancy for the period 1960-2005 were calculated for both countries. Subsequently, bivariate and multivariate linear regression analyses were performed and controlled for possibly confounding factors.
RESULTS:
When controlling for the underlying historical time trend, both countries appear to have experienced a deceleration of the pace of improvements in the years following the reform, for all the variables analyzed. In the case of Colombia, some of the previous gains in under-five mortality rate and crude mortality rate were, in fact, reversed.
CONCLUSIONS:
Neither reform seems to have had a decisive positive impact on the health outcomes analyzed for the defined time period of this research. This, in turn, may be a consequence of both internal characteristics of the respective reforms and external factors beyond the direct control of health reformers. Among the internal characteristics: underfunding, unbridled decentralization and inequitable access to care seem to have been the main constraints. Conversely, international economic adversities, high levels of rural and urban violence, along with entrenched income inequalities seem to have accounted for the highest burden among external factors.
From U Florida: Real time assessment of community health needs
http://www.ncbi.nlm.nih.gov/pubmed/22301551
Sci Transl Med. 2012 Feb 1;4(119):119mr2.
Real-time assessment of community health needs and concerns.
Cottler LB, Nagarajan R.
Source
Department of Epidemiology, University of Florida, Gainesville, FL 32606, USA.
Abstract
The August 2011 Clinical and Translational Science Awards conference "Using IT to Improve Community Health: How Health Care Reform Supports Innovation" convened four "Think Tank" sessions. This report summarizes the content of one session centered on "Social Networking: Community Connections and Health Outcomes." We discuss the efforts of HealthStreet to facilitate ongoing, real-time assessment of community health needs, concerns, and opportunities to participate in research.
Sci Transl Med. 2012 Feb 1;4(119):119mr2.
Real-time assessment of community health needs and concerns.
Cottler LB, Nagarajan R.
Source
Department of Epidemiology, University of Florida, Gainesville, FL 32606, USA.
Abstract
The August 2011 Clinical and Translational Science Awards conference "Using IT to Improve Community Health: How Health Care Reform Supports Innovation" convened four "Think Tank" sessions. This report summarizes the content of one session centered on "Social Networking: Community Connections and Health Outcomes." We discuss the efforts of HealthStreet to facilitate ongoing, real-time assessment of community health needs, concerns, and opportunities to participate in research.
Geomapping health data. "...an individual and community concern"?
http://www.ncbi.nlm.nih.gov/pubmed/22301553
Sci Transl Med. 2012 Feb 1;4(119):119mr4.
Geomapping health-related data.
Sayani S.
Source
Department of Health and Mental Hygiene, Baltimore, MD 21201, USA. SSayani@dhmh.state.md.us.
Abstract
In August 2011, scientists and policy-makers held a conference entitled "Using IT to Improve Community Health: How Health Care Reform Supports Innovation." One of the conference sessions was entitled "Geo-mapping: Framing health needs and issues as an individual and community concern." This Meeting Report describes how geographical information systems can be used to analyze health-related data for medical care and policy making.
Sci Transl Med. 2012 Feb 1;4(119):119mr4.
Geomapping health-related data.
Sayani S.
Source
Department of Health and Mental Hygiene, Baltimore, MD 21201, USA. SSayani@dhmh.state.md.us.
Abstract
In August 2011, scientists and policy-makers held a conference entitled "Using IT to Improve Community Health: How Health Care Reform Supports Innovation." One of the conference sessions was entitled "Geo-mapping: Framing health needs and issues as an individual and community concern." This Meeting Report describes how geographical information systems can be used to analyze health-related data for medical care and policy making.
From NIH: Meaningful use of electronic behavioral health data
http://www.ncbi.nlm.nih.gov/pubmed/22301552
Sci Transl Med. 2012 Feb 1;4(119):119mr3.
Meaningful use of electronic behavioral health data in primary health care.
Tai B, Boyle M, Ghitza U, Kaplan RM, Clark HW, Gersing K.
Source
Center for the Clinical Trials Network, National Institute on Drug Abuse, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20892, USA.
Abstract
In August 2011, scientists and policy-makers held a conference entitled "Using IT to Improve Community Health: How Health Care Reform Supports Innovation." One of the conference sessions was entitled "Electronic health records: Meaningful use implementation challenges, innovation, and regulations." This Meeting Report discusses the meaningful use of behavioral health data for the treatment of mental health and substance abuse conditions and optimization of behavioral wellness by primary care physicians.
Sci Transl Med. 2012 Feb 1;4(119):119mr3.
Meaningful use of electronic behavioral health data in primary health care.
Tai B, Boyle M, Ghitza U, Kaplan RM, Clark HW, Gersing K.
Source
Center for the Clinical Trials Network, National Institute on Drug Abuse, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20892, USA.
Abstract
In August 2011, scientists and policy-makers held a conference entitled "Using IT to Improve Community Health: How Health Care Reform Supports Innovation." One of the conference sessions was entitled "Electronic health records: Meaningful use implementation challenges, innovation, and regulations." This Meeting Report discusses the meaningful use of behavioral health data for the treatment of mental health and substance abuse conditions and optimization of behavioral wellness by primary care physicians.
Mental health reforms in Europe: Israel's law regarding rehabilitation
http://www.ncbi.nlm.nih.gov/pubmed/22302325
Psychiatr Serv. 2012 Feb 1;63(2):110-2.
Mental Health Reforms in Europe: Israel's Rehabilitation in the Community of Persons With Mental Disabilities Law: Challenges and Opportunities.
Aviram U, Ginath Y, Roe D.
Abstract
This column describes an innovative, government-sponsored, countrywide mental health reform focusing on rehabilitation and community integration of persons with serious mental illness, which was enacted into law in Israel in 2000. The reform was part of the country's efforts to shift the locus of treatment and care from psychiatric institutions to the community. The authors review preliminary evidence of the impact of reform and offer cautionary notes regarding the future direction of its implementation. The decade after the law's enactment saw an impressive increase in rehabilitation services, a significant reduction in the number of psychiatric beds, and major changes in government budget allocations. The authors examine factors that may endanger the viability of reform and discuss lessons to be learned from the Israeli experience. (Psychiatric Services 63:110-112, 2012; doi: 10.1176/appi.ps.201100009).
Psychiatr Serv. 2012 Feb 1;63(2):110-2.
Mental Health Reforms in Europe: Israel's Rehabilitation in the Community of Persons With Mental Disabilities Law: Challenges and Opportunities.
Aviram U, Ginath Y, Roe D.
Abstract
This column describes an innovative, government-sponsored, countrywide mental health reform focusing on rehabilitation and community integration of persons with serious mental illness, which was enacted into law in Israel in 2000. The reform was part of the country's efforts to shift the locus of treatment and care from psychiatric institutions to the community. The authors review preliminary evidence of the impact of reform and offer cautionary notes regarding the future direction of its implementation. The decade after the law's enactment saw an impressive increase in rehabilitation services, a significant reduction in the number of psychiatric beds, and major changes in government budget allocations. The authors examine factors that may endanger the viability of reform and discuss lessons to be learned from the Israeli experience. (Psychiatric Services 63:110-112, 2012; doi: 10.1176/appi.ps.201100009).
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