Oral nutritional supplement prevents weight loss and reduces side effects in patients in advanced lung cancer chemotherapy

Amino Acids - Weight loss in patients with cancer is caused by cancer cachexia and chemotherapy-induced nausea and vomiting. Recent developments in antiemetic drugs have substantially improved...     

Cachexia, gluconeogenesis and progressive weight loss in cancer patients

Several theories have been proposed to account for the pathogenesis of cachexia in cancer patients. One of these is that the tumor's greater avidity for essential amino acids can result in an amino acid imbalance, which in turn can cause cachexia. In this paper it is shown how, by known biochemical mechanisms, a tumor caused amino acid imbalance can lead to cachexia, progressive weight loss, abnormal gluconeogenesis and lactate recycling. Cachexia leads to a decreased dietary intake, but the cachectic cancer patient, unlike normal man, is unable to adapt. The reason is that the changeover of metabolic fuels from the fed state (glucose) to the starved state (lipids) is hormone regulated, but gluconeogenesis and lactate recycling are substrate regulated. Because of this substrate regulation of gluconeogenesis, the host will be unable to effectively decrease gluconeogenesis as long as the tumor persists in causing an amino acid imbalance.     

Combining simple blood tests to identify primary care patients with unexpected weight loss for cancer investigation: Clinical risk score development,internal validation,and net benefit analysis

BackgroundUnexpected weight loss (UWL) is a presenting feature of cancer in primary care. Existing research proposes simple combinations of clinical features (risk factors, symptoms, signs, and blood test data) that, when present, warrant cancer investigation. More complex combinations may modify cancer risk to sufficiently rule-out the need for investigation. We aimed to identify which clinical features can be used together to stratify patients with UWL based on their risk of cancer.Methods and findingsWe used data from 63,973 adults (age: mean 59 years, standard deviation 21 years; 42% male) to predict cancer in patients with UWL recorded in a large representative United Kingdom primary care electronic health record between January 1, 2000 and December 31, 2012. We derived 3 clinical prediction models using logistic regression and backwards stepwise covariate selection: Sm, symptoms-only model; STm, symptoms and tests model; Tm, tests-only model. Fifty imputations replaced missing data. Estimates of discrimination and calibration were derived using 10-fold internal cross-validation. Simple clinical risk scores are presented for models with the greatest clinical utility in decision curve analysis. The STm and Tm showed improved discrimination (area under the curve ≥ 0.91), calibration, and greater clinical utility than the Sm. The Tm was simplest including age-group, sex, albumin, alkaline phosphatase, liver enzymes, C-reactive protein, haemoglobin, platelets, and total white cell count. A Tm score of 5 balanced ruling-in (sensitivity 84.0%, positive likelihood ratio 5.36) and ruling-out (specificity 84.3%, negative likelihood ratio 0.19) further cancer investigation. A Tm score of 1 prioritised ruling-out (sensitivity 97.5%). At this threshold, 35 people presenting with UWL in primary care would be referred for investigation for each person with cancer referred, and 1,730 people would be spared referral for each person with cancer not referred. Study limitations include using a retrospective routinely collected dataset, a reliance on coding to identify UWL, and missing data for some predictors.ConclusionsOur findings suggest that combinations of simple blood test abnormalities could be used to identify patients with UWL who warrant referral for investigation, while people with combinations of normal results could be exempted from referral.

Dr. Brian D Nicholson and colleagues investigate whether combinations of routine blood tests could be used to stratify patients in UK with unexpected weight loss based on their risk of cancer.     

Cluster analysis of the national weight control registry to identify distinct subgroups maintaining successful weight loss

The National Weight Control Registry (NWCR) is the largest ongoing study of individuals successful at maintaining weight loss; the registry enrolls individuals maintaining a weight loss of at least 13.6 kg (30 lb) for a minimum of 1 year. The current report uses multivariate latent class cluster analysis to identify unique clusters of individuals within the NWCR that have distinct experiences, strategies, and attitudes with respect to weight loss and weight loss maintenance. The cluster analysis considers weight and health history, weight control behaviors and strategies, effort and satisfaction with maintaining weight, and psychological and demographic characteristics. The analysis includes 2,228 participants enrolled between 1998 and 2002. Cluster 1 (50.5%) represents a weight-stable, healthy, exercise conscious group who are very satisfied with their current weight. Cluster 2 (26.9%) has continuously struggled with weight since childhood; they rely on the greatest number of resources and strategies to lose and maintain weight, and report higher levels of stress and depression. Cluster 3 (12.7%) represents a group successful at weight reduction on the first attempt; they were least likely to be overweight as children, are maintaining the longest duration of weight loss, and report the least difficulty maintaining weight. Cluster 4 (9.9%) represents a group less likely to use exercise to control weight; they tend to be older, eat fewer meals, and report more health problems. Further exploration of the unique characteristics of these clusters could be useful for tailoring future weight loss and weight maintenance programs to the specific characteristics of an individual.     

Detection of risk factors that influence weight loss in patients undergoing radiotherapy

AimTo identify risk factors that influence weight loss in patients receiving radiotherapy.BackgroundIt is a well-known fact that cancer patients can be affected by malnutrition at the onset of the disease and during treatment due to the toxicity. Pretreatment weight loss alone does not predict those who will need nutritional supplementation. Instead, a variety of nutritional and tumor related factors needs to be taken into account.Material and methodsA retrospective study was conducted on 129 patients with different tumor locations. Weight loss was evaluated during radiotherapy and one month after treatment. The impact of age, ECOG, chemotherapy, pretreatment weight loss, tumor location, previous surgery and TNM were analyzed. We aimed to identify a high-risk group of patients before starting treatment.ResultsThe average net weight loss during radiotherapy and one month after treatment for this group of patients was 0.68 kg and 1.6 kg, respectively. Median weight loss during radiotherapy was 2.6 kg for head and neck (HN) patients and 0.27  kg for other tumor sites (p = 0.028). Median weight loss one month after radiotherapy was 3.7 kg for HN patients and 1.1 kg for the rest of the patients (p = 0.034). The median weight loss one month after treatment was 3.2 kg for patients receiving chemotherapy and 0.5 kg for those patients who did not receive chemotherapy (p < 0.001). A regression analysis determined that HN tumor location and the use of chemotherapy were independent risk factors.ConclusionsNutritional status must be monitored and managed before, during and after treatment. A variety of nutritional and tumor-related factors must be considered. According to our results, head and neck tumors and the use of chemotherapy are the only two factors considered statistically significant. Because patients continue to lose weight after treatment, we recommend close surveillance after radiotherapy.     

Low T3 syndrome in cancer patients in relation to weight loss, intravenous hyperalimentation therapy and age

In order to investigate the relation of weight loss and intravenous hyperalimentation therapy to low T3 syndrome, serum T3, T4. rT3 and TBG were determined by radioimmunoassay in 105 cancer patients. The cancer patients were classified into 3 groups, Group I, II and III depending on the grade of weight loss, ranging up to a 5% change in weight loss from a healthy condition, from 5 to 9%, and more than 10%, respectively. Cancer patients under age 59 showed no significant difference in serum T3, T4, rT3 and TBG among these 3 groups. However serum T3 and T3/T4 in cancer patients at age 60 and over were significantly reduced in group III, compared to groups I and II. Serum rT3 values were significantly elevated in group III of elderly cancer patients. The incidence of low T3 syndrome in group III of elderly cancer patients was also significantly higher than in groups I and II. In three out of 5 cancer patients with low T3 syndrome, serum T3 values increased after the intravenous hyperalimentation therapy, whereas no significant change in serum T3 values was observed in two patients who died within one day after the final examination. It is concluded that weight loss produced different effects on peripheral conversion of T4 to T3 between cancer patients under age 59 and over age 60 and glucose plays an important role in the pathogenesis of low T3 syndrome except cases with very poor prognosis.     

Inflammatory cytokines and malnutrition as related to risk for cardiovascular disease in hemodialysis patients

Malnutrition and inflammation are associated with end-stage renal disease (ESRD). Interleukin (IL)-6 and tumor necrosis factor alpha (TNF-alpha) powerfully predict death from cardiovascular disease. The aim of our study was to establish an association between markers of inflammation and parameters of malnutrition in patients on hemodialysis. The study population consisted of 42 hemodialysis patients with different parameters of malnutrition. Blood samples were taken after an overnight fast, and plasma lipid profiles (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides) were measured by using conventional enzymatic methods. Serum urea and creatinine levels were also measured by routine procedures. Plasma high-sensitivity C-reactive protein level (hs-CRP), TNF-alpha, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). Standard Doppler echo examinations were used to determine plaque on carotid arteries, and end-diastolic diameter (EDD) and ejection fraction (EF) were measured by echocardiography. Malnourished patients exhibited significantly greater evidence of cardiovascular disease and carotid plaques. Factor (principal component) analysis indicated 6 latent factors with 67.5% of the variance explained within all investigated parameters. Cluster analysis was used to distinguish the inflammatory markers and the nutritional markers from other parameters and to visualize similarities between variables. In summary, this cross-sectional study in hemodialysis patients found a high prevalence of malnutrition, inflammation, carotid plaques, and cardiovascular disease. Malnourished dialysis patients are more often found with cardiovascular disease and carotid plaques. In addition, these patients have higher levels of inflammatory cytokines, which may partly explain the elevated risk for atherosclerotic vascular disease.     

Skeletal muscle apoptosis is not increased in gastric cancer patients with mild-moderate weight loss

Numerous experimental and clinical studies have shown that skeletal muscle apoptotis may increase in wasting conditions and suggest that apoptosis might contribute to the loss of lean body mass. Data in cancer patients are still lacking. The present study aimed at verifying whether apoptosis was enhanced in the skeletal muscle of 16 patients with gastric cancer with respect to controls. A biopsy specimen was obtained from the rectus abdominis muscle. The occurrence of apoptosis in muscle biopsies was determined morphologically by the fluorescent transferase-mediated dUTP nick end labeling assay and by immunohistochemistry for caspase-3 and caspase-1. Mean weight loss was 6+/-2% in cancer patients and 0.5+/-0.1% in controls (p<0.0001). Serum albumin levels (g/dL) were 3.7+/-0.3 in cancer patients and 4.1+/-0.2 in controls (p<0.05). The percentage of apoptotic myonuclei was similar in cancer patients and in controls (1.5+/-0.3 versus 1.4+/-0.2, respectively; p=ns), in gastric cancer patients with mild (1.6+/-0.4) or moderate-severe weight loss (1.4+/-0.5) (p=ns), and in the different stages of disease (stages I-II: 1.5+/-0.7; stage III: 1.3+/-0.4; stage IV: 1.6+/-0.3; p=ns). By immunohistochemistry, caspase-1 and caspase-3 positive fibers were absent in controls and in neoplastic patients. Poly-ADP-ribosyl polymerase, a typical caspase-3 substrate whose processing is indicative of caspase-3 activation, was not cleaved in muscle biopsies of cancer patients. These data suggest that skeletal muscle apoptosis is not increased in neoplastic patients with mild-moderate weight loss and argue against the hypotheses that caspase-3 activation might be an essential step of myofibrillar proteolysis in cancer-related muscle wasting.     

Birth weight and subsequent risk of cancer

Background: We aimed to determine the association between self-reported birth weight and incident cancer in the Women's Health Initiative Observational Study cohort, a large multiethnic cohort of postmenopausal women. Methods: 65,850 women reported their birth weight by category (<6 lbs, 6–7 lbs 15 oz, 8–9 lbs 15 oz, and ≥10 lbs). All self-reported, incident cancers were adjudicated by study staff. We used Cox proportional hazards regression to estimate crude and adjusted hazard ratios (aHR) for associations between birth weight and: (1) all cancer sites combined, (2) gynecologic cancers, and (3) several site-specific cancer sites. Results: After adjustments, birth weight was positively associated with the risk of lung cancer (p = 0.01), and colon cancer (p = 0.04). An inverse trend was observed between birth weight and risk for leukemia (p = 0.04). A significant trend was not observed with breast cancer risk (p = 0.67); however, women born weighing ≥10 lbs were less likely to develop breast cancer compared to women born between 6 lbs-7 lbs 15 oz (aHR 0.77, 95% CI 0.63, 0.94). Conclusion: Birth weight category appears to be significantly associated with the risk of any postmenopausal incident cancer, though the direction of the association varies by cancer type.     

Subperiosteal gain and endosteal loss in protein-calorie malnutrition

Subperiosteal and medullary cavity diameters of 91 Guatemalan boys hospitalized with a diagnosis of protein-calorie malnutrition show a slight but significant increase in total width but a marked reduction at the endosteal surface, and in cortical area and percent cortical area, indicative of continuing subperiosteal apposition and a dramatic excess of endosteal resorption.     

Femoral artery remodeling after aerobic exercise training without weight loss in women

Background

It is currently unclear whether reductions in adiposity mediate the improvements in vascular health that occur with aerobic exercise. The purpose of this longitudinal study of 13 healthy women (33 ± 4 years old) was to determine whether 14 weeks of aerobic exercise would alter functional measures of vascular health, namely resting aortic pulse wave velocity (aPWV, an index of arterial stiffness), femoral artery diameter (D_FA), and femoral artery blood flow (BF_FA) independent of changes in adiposity.

Methods

Aerobic fitness was assessed as VO₂peak normalized to fat-free mass, and adiposity (percent body fat) was determined by dual energy x-ray absorptiometry. Serum concentrations of proteins associated with risk for cardiovascular disease, including C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), and leptin, were also measured. Subjects cycled for 50 minutes, 3 times per week.

Results

Aerobic fitness normalized to fat-free mass increased 6% (P = 0.03) whereas adiposity did not change. Resting D_FA increased 12% (P < 0.001) and resting shear rate decreased 28% (P = 0.007). Aortic PWV, and serum sICAM-1, CRP and leptin did not change with training.

Conclusion

Significant reductions in adiposity were not necessary for aerobic exercise training to bring about improvements in aerobic fitness and arterial remodeling. Peripheral arterial remodeling occurred without changes in central arterial stiffness or markers of inflammation.

     

SMpred: a support vector machine approach to identify structural motifs in protein structure without using evolutionary information

Knowledge of three dimensional structure is essential to understand the function of a protein. Although the overall fold is made from the whole details of its sequence, a small group of residues, often called as structural motifs, play a crucial role in determining the protein fold and its stability. Identification of such structural motifs requires sufficient number of sequence and structural homologs to define conservation and evolutionary information. Unfortunately, there are many structures in the protein structure databases have no homologous structures or sequences. In this work, we report an SVM method, SMpred, to identify structural motifs from single protein structure without using sequence and structural homologs. SMpred method was trained and tested using 132 proteins domains containing 581 motifs. SMpred method achieved 78.79% accuracy with 79.06% sensitivity and 78.53% specificity. The performance of SMpred was evaluated with MegaMotifBase using 188 proteins containing 1161 motifs. Out of 1161 motifs, SMpred correctly identified 1503 structural motifs reported in MegaMotifBase. Further, we showed that SMpred is useful approach for the length deviant superfamilies and single member superfamilies. This result suggests the usefulness of our approach for facilitating the identification of structural motifs in protein structure in the absence of sequence and structural homologs. The dataset and executable for the SMpred algorithm is available at http://www3.ntu.edu.sg/home/EPNSugan/index_files/SMpred.htm.     

Effect of a community-based weight management program on weight loss and cardiovascular disease risk factors

Objective: The purpose of our retrospective database analysis was to describe and evaluate the outcomes of a weight loss intervention in a community medical wellness center. Research Methods and Procedures: Four hundred eighteen overweight and obese adults entered the program between 2001 and 2004. Forty‐seven percent completed the 6‐month program designed using standards and recommendations established by the NIH, the American Dietetic Association, and the American Academy of Sports Medicine. Data analysis was limited to 198 participants (142 women, 56 men) completing the program. Results: Individuals completing the 6‐month program averaged a weight loss of 7.3% in men and 4.7% in women. Fasting lipids and blood glucose improved in both genders regardless of age. Outcomes including BMI and lipids improved in women regardless of menopausal status or hormone replacement therapy. There was a significant correlation between percentage weight loss and number of weekly counseling sessions attended and number of visits to the wellness center for exercise. Discussion: Participants who complete a structured community‐based weight management program can achieve significant weight loss and improvement in cardiovascular risk factors regardless of age, gender, or menopausal status. Our analysis suggests that national treatment guidelines/recommendations for weight management can be effectively implemented in a community medical wellness center. The relatively high drop‐out rate associated with this program suggests the need to identify strategies and techniques to enhance adherence and completion of programs.