GLIM criteria for the diagnosis of malnutrition - A consensus report from the global clinical nutrition community.

RATIONALE: This initiative is focused on building a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings. METHODS: In January 2016, the Global Leadership Initiative on Malnutrition (GLIM) was convened by several of the major global clinical nutrition societies. GLIM appointed a core leadership committee and a supporting working group with representatives bringing additional global diversity and expertise. Empirical consensus was reached through a series of face-to-face meetings, telephone conferences, and e-mail communications. RESULTS: A two-step approach for the malnutrition diagnosis was selected, i.e., first screening to identify "at risk" status by the use of any validated screening tool, and second, assessment for diagnosis and grading the severity of malnutrition. The malnutrition criteria for consideration were retrieved from existing approaches for screening and assessment. Potential criteria were subjected to a ballot among the GLIM core and supporting working group members. The top five ranked criteria included three phenotypic criteria (weight loss, low body mass index, and reduced muscle mass) and two etiologic criteria (reduced food intake or assimilation, and inflammation or disease burden). To diagnose malnutrition at least one phenotypic criterion and one etiologic criterion should be present. Phenotypic metrics for grading severity as Stage 1 (moderate) and Stage 2 (severe) malnutrition are proposed. It is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes. The recommended approach supports classification of malnutrition into four etiology-related diagnosis categories. CONCLUSION: A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed. Next steps are to secure further collaboration and endorsements from leading nutrition professional societies, to identify overlaps with syndromes like cachexia and sarcopenia, and to promote dissemination, validation studies, and feedback. The diagnostic construct should be re-considered every 3-5 years.

GLIM criteria for the diagnosis of malnutrition - A consensus report from the global clinical nutrition community.

RATIONALE: This initiative is focused on building a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings. METHODS: In January 2016, the Global Leadership Initiative on Malnutrition (GLIM) was convened by several of the major global clinical nutrition societies. GLIM appointed a core leadership committee and a supporting working group with representatives bringing additional global diversity and expertise. Empirical consensus was reached through a series of face-to-face meetings, telephone conferences, and e-mail communications. RESULTS: A two-step approach for the malnutrition diagnosis was selected, i.e., first screening to identify "at risk" status by the use of any validated screening tool, and second, assessment for diagnosis and grading the severity of malnutrition. The malnutrition criteria for consideration were retrieved from existing approaches for screening and assessment. Potential criteria were subjected to a ballot among the GLIM core and supporting working group members. The top five ranked criteria included three phenotypic criteria (non-volitional weight loss, low body mass index, and reduced muscle mass) and two etiologic criteria (reduced food intake or assimilation, and inflammation or disease burden). To diagnose malnutrition at least one phenotypic criterion and one etiologic criterion should be present. Phenotypic metrics for grading severity as Stage 1 (moderate) and Stage 2 (severe) malnutrition are proposed. It is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes. The recommended approach supports classification of malnutrition into four etiology-related diagnosis categories. CONCLUSION: A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed. Next steps are to secure further collaboration and endorsements from leading nutrition professional societies, to identify overlaps with syndromes like cachexia and sarcopenia, and to promote dissemination, validation studies, and feedback. The diagnostic construct should be re-considered every 3-5 years.

Protective effects of nebivolol from oxidative stress to prevent hypertension-related target organ damage.

Hypertension is one of the leading risk factors for morbidity and mortality in patients with cardiovascular and cerebrovascular diseases and renal impairment. It also leads to target organ damage (TOD), which worsens organ function and the patient's clinical status. Reactive oxygen species (ROS)-mediated oxidative stress may contribute significantly to TOD in patients with hypertension. NO (nitric oxide) is a paracrine factor derived from endothelial cells that has been shown to alleviate ROS-mediated oxidative damage. Nebivolol is a third-generation ß-blocker with vasodilator activity, both actions contributing to decreased blood pressure in hypertensive patients. Its vasodilatory function is mediated by the endothelial l-arginine NO pathway. Nebivolol increases the bioavailability of NO in the vasculature. Its efficacy and safety profile is comparable to other commonly used antihypertensive agents. In this article, we review the current literature to understand TOD secondary to oxidative stress in patients with hypertension and the role of nebivolol in its prevention. A better understanding of the underlying mechanisms by which nebivolol reduces ROS-mediated TOD will not only help in the development of targeted therapies but may also improve health outcomes in hypertensive patients.

Bone quality issues an matrix properties in OP cancellous bone.

There is increasing evidence nowadays that diseases or conditions, like osteoporosis (OP), which are conventionally defined in terms of bone quantity/mass, are also associated with concomitant changes at the bone matrix level. The present study examined the composition, density and mineral content of OP cancellous bone at the tissue level and the hardness values at the trabecular level to establish correlations between these variables. The results showed that changes in porosity (Bone volume/Tissue volume) are accompanied by changes in mineral content and in the hardness of individual trabeculae. In other words in OP there are both quantitative and qualitative effects that take place with the progress of this condition.

Adaptive servo-ventilation and deadspace: effects on central sleep apnoea.

Central Sleep Apnoea (CSA) occurs commonly in heart failure. Adaptive servo-ventilation (ASV) and deadspace (DS) have been shown in research settings to reverse CSA. The likely mechanism for this is the increase of PaCO(2) above the apnoeic threshold. However the role of increasing FiCO(2) on arousability remains unclear. To compare the effects of ASV and DS on sleep and breathing, in particular effects on Arousal Index (ArI), ten male patients with heart failure and CSA were studied during three nights with polysomnography plus measurements of PetCO(2). The order of the interventions control (C), ASV and DS was randomized. ASV and DS caused similar reductions in apnoea-hypopnoea index [(C) 30.0 +/- 6.6, (ASV) 14.0 +/- 3.8, (DS) 15.9 +/- 4.7 e h(-1); both P < 0.05]. However, DS was associated with decreased total sleep time compared with C (P < 0.02) and increased spontaneous ArI compared to C and ASV (both P < 0.01). Only DS was associated with increased DeltaPetCO(2) from resting wakefulness to eupnic sleep [(C) 2.1 +/- 0.9, (ASV) 1.3 +/- 1.0, (DS) 5.6 +/- 0.5 mmHg; P = 0.01]. ASV and DS both stabilized ventilation however DS application also increased sleep fragmentation with negative impacts on sleep architecture. We speculate that this effect is likely to be mediated by increased PetCO(2) and respiratory effort associated with DS application.

Diuretics for heart failure.

BACKGROUND: Chronic heart failure is a major cause of morbidity and mortality world-wide. Diuretics are regarded as the first-line treatment for patients with congestive heart failure since they provide symptomatic relief. The effects of diuretics on disease progression and survival remain unclear. OBJECTIVES: To assess the harms and benefits of diuretics for chronic heart failure SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Issue 2 2004), MEDLINE 1966-2004, EMBASE 1980-2004 and HERDIN database. We hand searched pertinent journals and reference lists of papers were inspected. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Only double-blinded randomised controlled trials of diuretic therapy comparing one diuretic with placebo, or one diuretic with another active agent (e.g. ACE inhibitors, digoxin) in patients with chronic heart failure were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted the data and assessed the eligibility and methodological quality of each trial. Extracted data were entered into the Review Manager 4.2 computer software, and analysed by determining the odds ratio for dichotomous data, and difference in means for continuous data, of the treated group compared with controls. The likelihood of heterogeneity of the study population was assessed by the Chi-square test. If there was no evidence of statistical heterogeneity and pooling of results was clinically appropriate, a combined estimate was obtained using the fixed-effects model. MAIN RESULTS: We included 14 trials (525 participants), 7 were placebo-controlled, and 7 compared diuretics against other agents such as ACE inhibitors or digoxin. We analysed the data for mortality and for worsening heart failure. Mortality data were available in 3 of the placebo-controlled trials (202 participants). Mortality was lower for participants treated with diuretics than for placebo, odds ratio (OR) for death 0.24, 95% confidence interval (CI) 0.07 to 0.83; P = 0.02. Admission for worsening heart failure was reduced in those taking diuretics in two trials (169 participants), OR 0.07 (95% CI 0.01 to 0.52; P = 0.01). In four trials comparing diuretics to active control (91 participants), diuretics improved exercise capacity in participants with CHF, difference in means WMD 0.72 , 95% CI 0.40 to 1.04; P < 0.0001. AUTHORS' CONCLUSIONS: The available data from several small trials show that in patients with chronic heart failure, conventional diuretics appear to reduce the risk of death and worsening heart failure compared to placebo. Compared to active control, diuretics appear to improve exercise capacity.

Echocardiographic features and brain natriuretic peptides in patients presenting with heart failure and preserved systolic function.

OBJECTIVE: To characterise patients who appear to fulfil the diagnosis of heart failure with preserved systolic function clinically, echocardiographically, and by concentrations of brain-type natriuretic peptide (BNP). METHODS: 102 new cases of heart failure were identified over 24 months in 213 patients referred to a rapid access heart failure clinic. Patients with heart failure and preserved systolic function with contemporary markers of diastolic function were assessed to evaluate their cardiac status further. RESULTS: Forty patients (39%) had an ejection fraction (EF) < 45% and 62 (61%) had an EF > or = 45%. Of these 62 patients, 30 (48%) fulfilled the case definition of diastolic heart failure. The remaining 32 (52%) had neither an EF < 45% nor abnormalities of diastolic function. Dobutamine stress echocardiography was performed on 26 (42%) patients with EF > or = 45%, which provided an alternative explanation for symptoms in 15 (58%) patients. Concentrations of BNP were higher in patients with diastolic abnormalities (mean (SEM) 101.4 (32.5) pg/ml v 58.4 (6.78) pg/ml, p = 0.042) and with no diastolic abnormalities (199 (37.9) pg/ml v 58.4 (6.78) pg/ml, p < 0.0001) than in patients with no heart failure. CONCLUSION: Among ambulatory patients presenting with suspected heart failure in the community 19% have systolic dysfunction, 14% have diastolic dysfunction, and 15% seemingly have heart failure with neither systolic nor diastolic dysfunction. A new understanding, including alternative parameters of diastolic function, seems to be necessary to classify patients with heart failure and preserved systolic function.

Infrared intensities of some SiH-containing compounds in the gas-phase.

Infrared intensities measured in the gas-phase are reported for CH3SiH3, CH3SiD3, (CH3)2SiH2, (CH3)2SiD2, (SiH3)2CH2, (SiD3)2CH2, Si2H6, SiH2Cl2 and (SiH3)2O. These are compared with theoretical estimates from HF, MP2 and B3LYP calculations with the 6-311G** basis set. Literature values of nuCH intensities per bond from 18 compounds correlate linearly with the values calculated at MP2 and B3LYP levels: the corresponding HF plot is slightly curved. The new HC(Si) data fit these correlations adequately. In similar plots for SiH stretching intensity, the point for SiH2Cl2 is displaced, especially at the HF level. The lack of relation of nuCH or nuSiH intensity to Mulliken atomic charge points to the effect of varying atomic charge flux in the parameter thetamu/thetar. Anomalies associated with nuSiH intensities influenced by chlorine or OR substitution and previously explained by d(pi)-p(pi) bonding are attributed instead to charge flux variation. For silyl groups, deformation band intensities are roughly additive according to the number of such groups. However, this is not the case for the methyl symmetric deformation bands in methyl and dimethyl silanes.

Cachexia in malaria and heart failure: therapeutic considerations in clinical practice.

Cachexia is an independent prognostic marker of survival in many chronic diseases including heart failure and malaria. Morbidity and mortality from malaria is high in most of the third world where it presents a very challenging public health problem. Malaria may present in the UK as fever in the returning traveller or as fever in overseas visitors. How and why cachexia develops in malaria in a manner similar to the cachexia of chronic heart failure and the treatment strategies that would alter outcomes in both diseases are discussed in this review.

Effect of CO2 inhalation on central sleep apnea and arousals from sleep.

BACKGROUND: CO(2) inhalation reduces central sleep apnea (CSA) in patients with congestive heart failure (CHF) and idiopathic CSA. CO(2) is also a stimulus for cortical arousal, which has been linked to increased sympathetic nerve activity (SNA) and increased mortality in CHF patients with CSA. OBJECTIVE: We have tested the hypothesis that during sleep, inhalation of CO(2) sufficient to reduce the apnea-hypopnea index (AHI) would not reduce the arousal index (AroI). METHODS: In 10 male patients with CSA (7 with CHF and 3 with idiopathic CSA), the inspired CO(2) concentration was increased to raise the sleeping end-tidal CO(2) by 2-4 mm Hg during established stage 2 sleep. Each intervention was maintained for a 10-min period. Sleep stage was monitored with electroencephalograms, electrooculograms, submental electromyogram, airflow with pneumotachometer and respiratory effort and blood gases with oxygen saturation and end-tidal CO(2). During periods of air and CO(2) breathing, AHI and AroI were compared with paired t tests; patients acted as their own controls. RESULTS: Inhalation of CO(2) produced a significant reduction in AHI (mean +/- SEM) from 74.4 +/- 12.4 events/h during air breathing to 25.8 +/- 7.8 events/h with CO(2) inhalation (p = 0.002). However, the AroI was not significantly different between the two conditions, air 67.8 +/- 12.3 events/h and CO(2) inhalation 52.8 +/- 12.4 events/h (p = 0.264). CONCLUSION: CO(2) inhalation reverses CSA but not arousals from sleep. Our findings highlight the need for treatment options that reduce both respiratory events and decrease arousals from sleep, with their associated SNA sequelae.

Exercise based rehabilitation for heart failure.

BACKGROUND: The prevalence of chronic heart failure is increasing, and increases with increasing age. Major symptoms include breathlessness and restricted activities of daily living due to reduced functional capacity, which in turn affects quality of life. Exercise training has been shown to be effective in patients with coronary heart disease and has been proposed as an intervention to improve exercise tolerance in patients with heart failure. OBJECTIVES: To determine the effectiveness of exercise based interventions compared with usual medical care on the mortality, morbidity, exercise capacity and health related quality of life, of patients with heart failure. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (The Cochrane Library Issue 2, 2001), MEDLINE (2000 to March 2001), EMBASE (1998 to March 2001), CINAHL (1984 to March 2001) and reference lists of articles. We also sought advice from experts. SELECTION CRITERIA: RCTs of exercise based interventions. The comparison group was usual medical care as defined by the study, or placebo. Adults of all ages with chronic heart failure. Only those studies with criteria for diagnosis of heart failure (based on clinical findings or objective indices) have been included. DATA COLLECTION AND ANALYSIS: Studies were selected, and data were abstracted, independently by two reviewers. Authors were contacted where possible to obtain missing information. MAIN RESULTS: Twenty-nine studies met the inclusion criteria, with 1126 patients randomised. The majority of studies included both patients with primary and secondary heart failure, NYHA class II or III. None of the studies specifically examined the effect of exercise training on mortality and morbidity as most were of short duration. Exercise training significantly increased VO(2) max by (WMD random effects model) 2.16 ml/kg/min (95% CI 2.82 to 1.49), exercise duration increased by 2.38 minutes (95% CI 2.85 to 1.9), work capacity by 15.1 Watts (95% CI 17.7 to 12.6) and distance on the six minute walk by 40.9 metres (95% CI 64.7 to 17.1). Improvements in VO(2) max were greater for training programmes of greater intensity and duration. HRQoL improved in the seven of nine trials that measured this outcome. REVIEWERS' CONCLUSIONS: Exercise training improves exercise capacity and quality of life in patients mild to moderate heart failure in the short term. There is currently no information regarding the effect of exercise training on clinical outcomes. The findings are based on small-scale trials in patients who are unrepresentative of the total population of patients with heart failure. Other groups (more severe patients, the elderly, women) may also benefit. Large-scale pragmatic trials of exercise training of longer duration, recruiting a wider spectrum of patients are needed to address these issues.

Effects of carvedilol on left ventricular remodelling in chronic stable heart failure: a cardiovascular magnetic resonance study.

BACKGROUND: The ability of beta blockers to improve left ventricular function has been demonstrated, but data on the effects on cardiac remodelling are limited. OBJECTIVE: To investigate, using cardiovascular magnetic resonance (CMR), the effects of carvedilol on left ventricular remodelling in patients with chronic stable heart failure and left ventricular systolic dysfunction caused by coronary artery disease. DESIGN: Randomised, double blind, placebo controlled study. SETTING: Chronic stable heart failure. PATIENTS AND INTERVENTION: 34 patients with chronic stable heart failure and left ventricular systolic function taking part in the CHRISTMAS trial (double blind carvedilol v placebo) underwent CMR before randomisation and after six months of treatment. MAIN OUTCOME MEASURE: Left ventricular remodelling at six months. RESULTS: The carvedilol and placebo groups were well balanced at baseline, with no significant intergroup differences. Over the study period, there was a significant reduction in end systolic volume index (ESV(I)) and end diastolic volume index (EDV(I)) between the carvedilol and the placebo group (carvedilol -9 v placebo +3 ml/m2, p = 0.0004; carvedilol -8 v placebo 0 ml/m2, p = 0.05). The ejection fraction increased significantly between the groups (carvedilol +3% v placebo -2%, p = 0.003). CONCLUSIONS: Treatment of chronic stable heart failure with carvedilol results in significant improvement in left ventricular volumes and function. These effects might contribute to the benefits of carvedilol on mortality and morbidity in patients with chronic heart failure.

N-(4-hydroxyphenyl) retinamide (4HPR) enhances TRAIL-mediated apoptosis through enhancement of a mitochondrial-dependent amplification loop in ovarian cancer cell lines.

The majority of ovarian cancer cells are resistant to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Subtoxic concentrations of the semisynthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR) enhanced TRAIL-mediated apoptosis in ovarian cancer cell lines but not in immortalized nontumorigenic ovarian epithelial cells. The enhancement of TRAIL-mediated apoptosis by 4HPR was not due to changes in the levels of proteins known to modulate TRAIL sensitivity. The combination of 4HPR and TRAIL enhanced cleavage of multiple caspases in the death receptor pathway (including the two initiator caspases, caspase-8 and caspase-9). The 4HPR and TRAIL combination leads to mitochondrial permeability transition, significant increase in cytochrome c release, and increased caspase-9 activation. Caspase-9 may further activate caspase-8, generating an amplification loop. Stable overexpression of Bcl-xL abrogates the interaction between 4HPR and TRAIL at the mitochondrial level by blocking cytochrome c release. As a consequence, a decrease in activation of caspase-9, caspase-8, and TRAIL-mediated apoptosis occurs. These results indicate that the enhancement in TRAIL-mediated apoptosis induced by 4HPR is due to the increase in activation of multiple caspases involving an amplification loop via the mitochondrial-death pathway. These findings offer a promising and novel strategy for the treatment of ovarian cancer.

Exercise training meta-analysis of trials in patients with chronic heart failure (ExTraMATCH).

OBJECTIVE: To determine the effect of exercise training on survival in patients with heart failure due to left ventricular systolic dysfunction. DESIGN: Collaborative meta-analysis. Inclusion criteria Randomised parallel group controlled trials of exercise training for at least eight weeks with individual patient data on survival for at least three months. Studies reviewed Nine datasets, totalling 801 patients: 395 received exercise training and 406 were controls. MAIN OUTCOME MEASURE: Death from all causes. RESULTS: During a mean (SD) follow up of 705 (729) days there were 88 (22%) deaths in the exercise arm and 105 (26%) in the control arm. Exercise training significantly reduced mortality (hazard ratio 0.65, 95% confidence interval, 0.46 to 0.92; log rank chi(2) = 5.9; P = 0.015). The secondary end point of death or admission to hospital was also reduced (0.72, 0.56 to 0.93; log rank chi(2) = 6.4; P = 0.011). No statistically significant subgroup specific treatment effect was observed. CONCLUSION: Meta-analysis of randomised trials to date gives no evidence that properly supervised medical training programmes for patients with heart failure might be dangerous, and indeed there is clear evidence of an overall reduction in mortality. Further research should focus on optimising exercise programmes and identifying appropriate patient groups to target.

Material properties of subchondral bone from patients with osteoporosis or osteoarthritis by microindentation testing and electron probe microanalysis.

Cancellous bone from patients with osteoarthritis (OA) has a reduced material density and appears to be undermineralized. It is hypothesized that this will result in a reduction in the mechanical stiffness and strength of the bone matrix. In this study, bone was obtained from superior and inferior sites, subjected to relatively high and low loads, respectively, from human femoral heads retrieved after surgery for osteoporotic hip fracture (OP), or for hip arthroplasty due to OA. Microindentation testing was used to measure the hardness of cancellous bone at various depths from the subchondral bone plate. The elemental composition from immediately adjacent microscopic sites was determined using electron probe microanalysis (EPMA). Overall, OA bone was found to have hardness values that were 7% lower than those from OP bone. Bone from the inferior site was harder than that from the superior in both diseases except in female OP patients. There was no variation with depth below the subchondral plate and no difference between sexes. No difference was found in the composition of the bone from the different disease groups and no correlation was found between hardness and any of the composition measurements. Though only an indirect measurement of stiffness, the reduction in hardness values supports the hypothesis that OA bone has a reduced elastic modulus.

Myocardial viability as a determinant of the ejection fraction response to carvedilol in patients with heart failure (CHRISTMAS trial): randomised controlled trial.

BACKGROUND: The improvement in left-ventricular ejection fraction (LVEF) in response to beta blockers is heterogeneous in patients with heart failure due to ischaemic heart disease, possibly indicating variations in the myocardial substrate underlying left-ventricular dysfunction. We investigated whether improvement in LVEF was associated with the volume of hibernating myocardium (viable myocardium with contractile failure). METHODS: We did a double-blind, randomised trial to compare placebo and carvedilol for 6 months in individuals with stable, chronic heart failure due to ischaemic left-ventricular systolic dysfunction. We enrolled 489 patients, of whom 387 were randomised. Patients were designated hibernators or non-hibernators according to the volume of hibernating myocardium. The primary endpoint was change in LVEF, measured by radionuclide ventriculography, in hibernators versus non-hibernators, on carvedilol compared with placebo. Analysis was by intention to treat. RESULTS: 82 patients dropped out of the study because of adverse events, withdrawal of consent, or failure to complete the investigation. Thus, 305 (79%) were analysed. LVEF was unchanged with placebo (mean change -0.4 [SE 0.9] and -0.4 [0.8] for non-hibernators and hibernators, respectively) but increased with carvedilol (2.5 [0.9] and 3.2 [0.8], respectively; p<0.0001 compared with baseline). Mean placebo-subtracted change in LVEF was 3.2% (95% CI 1.8-4.7; p=0.0001) overall, and 2.9% (0.7-5.1; p=0.011) and 3.6% (1.7-5.4; p=0.0002) in non-hibernators and hibernators, respectively. Effect of hibernator status on response of LVEF to carvedilol was not significant (0.7 [-2.2 to 3.5]; p=0.644). However, patients with more myocardium affected by hibernation or by hibernation and ischaemia had a greater increase in LVEF on carvedilol (p=0.0002 and p=0.009, respectively). INTERPRETATION: Some of the effect of carvedilol on LVEF might be mediated by improved function of hibernating or ischaemic myocardium, or both. Medical treatment might be an important adjunct or alternative to revascularisation for patients with hibernating myocardium.