On May 4, 2005, the system for allocation of deceased donor lungs for transplant in the United States changed from allocation based on waiting time to allocation based on the lung allocation score ...(LAS). We sought to determine the effect of the LAS on lung transplantation in the United States.
Organ Procurement and Transplantation Network data on listed and transplanted patients were analyzed for 5 calendar years before implementation of the LAS (2000-2004), and compared with data from 6 calendar years after implementation (2006-2011). Counts were compared between eras using the Wilcoxon rank sum test. The rates of transplant increase within each era were compared using an F-test. Survival rates computed using the Kaplan-Meier method were compared using the log-rank test.
After introduction of the LAS, waitlist deaths decreased significantly, from 500/year to 300/year; the number of lung transplants increased, with double the annual increase in rate of lung transplants, despite no increase in donors; the distribution of recipient diagnoses changed dramatically, with significantly more patients with fibrotic lung disease receiving transplants; age of recipients increased significantly; and 1-year survival had a small but significant increase.
Allocating lungs for transplant based on urgency and benefit instead of waiting time was associated with fewer waitlist deaths, more transplants performed, and a change in distribution of recipient diagnoses to patients more likely to die on the waiting list.
Aging and diabetes mellitus are 2 well-known risk factors for cardiovascular disease (CVD). During the past 50 years, there has been an dramatic increase in life expectancy with a simultaneous ...increase in the prevalence of diabetes mellitus in the older population. This large number of older individuals with diabetes mellitus is problematic given that CVD risk associated with aging and diabetes mellitus. In this review, we summarize epidemiological data relating to diabetes mellitus and CVD, with an emphasis on the aging population. We then present data on hyperglycemia as a risk factor for CVD and review the current knowledge of age-related changes in glucose metabolism. Next, we review the role of obesity in the pathogenesis of age-related glucose dysregulation, followed by a summary of the results from major randomized controlled trials that focus on cardiovascular risk reduction through glycemic control, with a special emphasis on older adults. We then conclude with our proposed model of aging that body composition changes and insulin resistance link possible dysregulation of physiological pathways leading to obesity and diabetes mellitus—both forms of accelerated aging—and risks for CVD.
In cancer patients, a high pre-treatment neutrophil-to-lymphocyte ratio (NLR) is associated with poorer survival outcomes. Significant variation in the magnitude of this association has been observed ...between studies, but sources of this variation are poorly understood. Here, we explore differences in the prognostic potential of NLR between patient subgroups stratified by demographic and clinical characteristics using a retrospective cohort of 5,363 patients treated at Moffitt Cancer Center (Tampa, FL). We identify patients for whom NLR has maximum prognostic potential via adjusted hazard ratios (HRs) calculated using multivariable Cox proportional hazards models and area under the curve analysis. NLR demonstrates stronger associations (HRs > 2) with survival among African-American patients, patients receiving radiation therapy, stage IV patients, and melanoma patients when compared with the overall study population (HR = 1.58). Sensitivity and specificity of NLR as a prognostic marker are also higher in these patient subgroups, and increase further with combinations of multiple "high-risk" demographic or clinical characteristics. In summary, NLR may have greater prognostic value in patients with certain demographic and clinical features. Future prospective studies could validate this hypothesis, after further characterization of populations in which NLR has maximum prognostic potential and the identification of meaningful thresholds for risk stratification.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Incretins are gut hormones that are secreted from enteroendocrine cells into the blood within minutes after eating. One of their many physiological roles is to regulate the amount of insulin that is ...secreted after eating. In this manner, as well as others to be described in this review, their final common raison d'être is to aid in disposal of the products of digestion. There are two incretins, known as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1), that share many common actions in the pancreas but have distinct actions outside of the pancreas. Both incretins are rapidly deactivated by an enzyme called dipeptidyl peptidase 4 (DPP4). A lack of secretion of incretins or an increase in their clearance are not pathogenic factors in diabetes. However, in type 2 diabetes (T2DM), GIP no longer modulates glucose-dependent insulin secretion, even at supraphysiological (pharmacological) plasma levels, and therefore GIP incompetence is detrimental to beta-cell function, especially after eating. GLP-1, on the other hand, is still insulinotropic in T2DM, and this has led to the development of compounds that activate the GLP-1 receptor with a view to improving insulin secretion. Since 2005, two new classes of drugs based on incretin action have been approved for lowering blood glucose levels in T2DM: an incretin mimetic (exenatide, which is a potent long-acting agonist of the GLP-1 receptor) and an incretin enhancer (sitagliptin, which is a DPP4 inhibitor). Exenatide is injected subcutaneously twice daily and its use leads to lower blood glucose and higher insulin levels, especially in the fed state. There is glucose-dependency to its insulin secretory capacity, making it unlikely to cause low blood sugars (hypoglycemia). DPP4 inhibitors are orally active and they increase endogenous blood levels of active incretins, thus leading to prolonged incretin action. The elevated levels of GLP-1 are thought to be the mechanism underlying their blood glucose-lowering effects.
Incretins in obesity and diabetes Chia, Chee W.; Egan, Josephine M.
Annals of the New York Academy of Sciences,
February 2020, Volume:
1461, Issue:
1
Journal Article
Peer reviewed
Open access
Incretins are hormones secreted from enteroendocrine cells after nutrient intake that stimulate insulin secretion from β cells in a glucose‐dependent manner. Glucose‐dependent insulinotropic ...polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) are the only two known incretins. Dysregulation of incretin secretion and actions are noted in diseases such as obesity and diabetes. In this review, we first summarize our traditional understanding of the physiology of GIP and GLP‐1, and our current knowledge of the relationships between GIP and GLP‐1 and obesity and diabetes. Next, we present the results from major randomized controlled trials on the use of GLP‐1 receptor agonists for managing type 2 diabetes, and emerging data on treating obesity and prediabetes. We conclude with a glimpse of the future with possible complex interactions between nutrients, gut microbiota, the endocannabinoid system, and enteroendocrine cells.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Resistant hypertension (RH) is defined as above-goal elevated blood pressure (BP) in a patient despite the concurrent use of 3 antihypertensive drug classes, commonly including a long-acting calcium ...channel blocker, a blocker of the renin-angiotensin system (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker), and a diuretic. The antihypertensive drugs should be administered at maximum or maximally tolerated daily doses. RH also includes patients whose BP achieves target values on ≥4 antihypertensive medications. The diagnosis of RH requires assurance of antihypertensive medication adherence and exclusion of the “white-coat effect” (office BP above goal but out-of-office BP at or below target). The importance of RH is underscored by the associated risk of adverse outcomes compared with non-RH. This article is an updated American Heart Association scientific statement on the detection, evaluation, and management of RH. Once antihypertensive medication adherence is confirmed and out-of-office BP recordings exclude a white-coat effect, evaluation includes identification of contributing lifestyle issues, detection of drugs interfering with antihypertensive medication effectiveness, screening for secondary hypertension, and assessment of target organ damage. Management of RH includes maximization of lifestyle interventions, use of long-acting thiazide-like diuretics (chlorthalidone or indapamide), addition of a mineralocorticoid receptor antagonist (spironolactone or eplerenone), and, if BP remains elevated, stepwise addition of antihypertensive drugs with complementary mechanisms of action to lower BP. If BP remains uncontrolled, referral to a hypertension specialist is advised.
The potential of natural products to prevent obesity have been investigated, with evidence to suggest that chitosan has anti-obesity effects. The current experiment investigated the anti-obesity ...potential of prawn shell derived chitosan on a range of variables relevant to obesity in a pig model. The two dietary treatment groups included in this 63 day study were: T1) basal diet and T2) basal diet plus 1000 ppm chitosan (n = 20 gilts per group (70 ± 0.90 kg). The parameter categories which were assessed included: performance, nutrient digestibility, serum leptin concentrations, nutrient transporter and digestive enzyme gene expression and gut microbial populations. Pigs offered chitosan had reduced feed intake and final body weight (P< 0.001), lower ileal digestibility of dry matter (DM), gross energy (GE) (P< 0.05) and reduced coefficient of apparent total tract digestibility (CATTD) of gross energy and nitrogen (P<0.05) when compared to the basal group. Fatty acid binding protein 2 (FABP2) gene expression was down-regulated in pigs offered chitosan (P = 0.05) relative to the basal diet. Serum leptin concentrations increased (P< 0.05) in animals offered the chitosan diet compared to pigs offered the basal diet. Fatness traits, back-fat depth (mm), fat content (kg), were significantly reduced while lean meat (%) was increased (P<0.05) in chitosan supplemented pigs. Pigs offered chitosan had decreased numbers of Firmicutes in the colon (P <0.05), and Lactobacillus spp. in both the caecum (P <0.05) and colon (P <0.001). Bifidobacteria populations were increased in the caecum of animals offered the chitosan diet (P <0.05). In conclusion, these findings suggest that prawn shell chitosan has potent anti-obesity/body weight control effects which are mediated through multiple biological systems in vivo.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hypertension is a major risk factor for cardiovascular and renal diseases in the United States and worldwide. Obesity accounts for much of the risk for primary hypertension through several ...mechanisms, including neurohormonal activation, inflammation, and kidney dysfunction. As the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed. Lifestyle modification, including diet, reduced sedentariness, and increased physical activity, is usually recommended for patients with obesity; however, the long-term success of these strategies for reducing adiposity, maintaining weight loss, and reducing blood pressure has been limited. Effective pharmacotherapeutic and procedural strategies, including metabolic surgeries, are additional options to treat obesity and prevent or attenuate obesity hypertension, target organ damage, and subsequent disease. Medications can be useful for short- and long-term obesity treatment; however, prescription of these drugs is limited. Metabolic surgery is effective for producing sustained weight loss and for treating hypertension and metabolic disorders in many patients with severe obesity. Unanswered questions remain related to the mechanisms of obesity-related diseases, long-term efficacy of different treatment and prevention strategies, and timing of these interventions to prevent obesity and hypertension-mediated target organ damage. Further investigation, including randomized controlled trials, is essential to addressing these questions, and emphasis should be placed on the prevention of obesity to reduce the burden of hypertensive cardiovascular and kidney diseases and subsequent mortality.
White clover (Trifolium repens L.; clover) can offer a superior nutritional feed compared with perennial ryegrass (Lolium perenne L.; PRG) and offers an additional or alternative source (or both) of ...N for herbage production. The objective of this study was to investigate the effect of including clover into PRG swards receiving 150 (Cl150) or 250 kg of N/ha (Cl250) compared with a PRG-only sward receiving 250 kg of N/ha (Gr250) on herbage production, milk production, and herbage dry matter intake (DMI) in an intensive grass-based spring calving milk production system over 2 full lactations. A farm systems experiment was established in February 2013, and conducted over 2 grazing seasons 2013 (yr 1) and 2014 (yr 2). In February 2013 (yr 1), 42 Holstein-Friesian spring-calving dairy cows, and in February 2014 (yr 2), 57 Holstein-Friesian spring-calving dairy cows were allocated to graze the Cl150, Cl250, and Gr250 swards (n = 14 in yr 1 and n = 19 in yr 2) from February to November, at a stocking rate of 2.74 cows/ha. Herbage DMI was estimated twice in yr 1 (May and September) and 3 times in yr 2 (May, July, and September). Treatment did not have a significant effect on annual herbage production. Sward clover content was greater on the Cl150 treatment than the Cl250 treatment. The cows grazing both clover treatments (Cl250 and Cl150) produced more milk than the cows grazing Gr250 from June until the end of the grazing season. A significant treatment by measurement period interaction was observed on total DMI. In May, the cows on the Cl250 treatment had the greatest DMI. In July, the cows on the clover treatments had greater DMI than those on the Gr250 treatment, whereas in September, the cows on the Cl150 treatment had the lowest DMI. In conclusion, including clover in a PRG sward grazed by spring-calving dairy cows can result in increased animal performance, particularly in the second half of lactation. Reducing N fertilizer application to 150 kg of N/ha on grass-clover swards did not reduce herbage production compared with grass-only swards receiving 250 kg of N/ha. White clover can play an integral role in intensive grazing systems in terms of animal performance and herbage production.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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