The impact of saliva collection methods on measured salivary biomarker levels.

Saliva diagnostics have become increasingly popular due to their non-invasive nature and patient-friendly collection process. Various collection methods are available, yet these are not always well standardized for either quantitative or qualitative analysis. In line, the objective of this study was to evaluate if measured levels of various biomarkers in the saliva of healthy individuals were affected by three distinct saliva collection methods: 1) unstimulated saliva, 2) chew stimulated saliva, and 3) oral rinse. Saliva samples from 30 healthy individuals were obtained by the three collection methods. Then, the levels of various salivary biomarkers such as proteins and ions were determined. It was found that levels of various biomarkers obtained from unstimulated saliva were comparable to those in chew stimulated saliva. The levels of potassium, sodium, and amylase activity differed significantly among the three collection methods. Levels of all biomarkers measured using the oral rinse method significantly differed from those obtained from unstimulated and chew-stimulated saliva. In conclusion, both unstimulated and chew-stimulated saliva provided comparable levels for a diverse group of biomarkers. However, the results obtained from the oral rinse method significantly differed from those of unstimulated and chew-stimulated saliva, due to the diluted nature of the saliva extract.

The association between polypharmacy and malnutrition(risk) in older people: A systematic review.

BACKGROUND & AIM: Malnutrition adversely influences a broad range of physical and psychological symptoms. Although polypharmacy is often mentioned to be associated with malnutrition, especially in older people it is unclear to what extent. The aim of this systematic review was to investigate the extent of the association between polypharmacy and malnutrition in older people. METHODS: The methodology followed the guidelines of the Cochrane Collaboration. Literature search was performed in PubMed, CINAHL and Embase. The population of interest for this systematic review were people of 65 years and older with polypharmacy. Because there is ambiguity with regard to the actual definition of malnutrition and polypharmacy, in this systematic review all articles describing malnutrition prevalence rates were included, regardless of the criteria used. Both observational and intervention studies were screened for eligibility. Selection and quality assessment of the included full text studies was assessed by two reviewers independently. A level of evidence and methodological quality score was adjudged to each article based on this assessment. RESULTS: A total of 3126 studies were retrieved by the literature search, of which seven studies were included in this systematic review. There was considerable variation in the definition of polypharmacy between studies. Two studies defined polypharmacy as the use of five or more drugs, two studies as the use of six or more drugs, two studies provided a mean and standard deviation that corresponded to the minimum of five drugs, and one study distinguished between polypharmacy (five or more drugs) and excessive polypharmacy (ten or more drugs). However, all studies showed a statistically significant association between (the risk) of becoming malnourished and polypharmacy regardless the instrument or criterion used to define risk of malnutrition. Studies presented the associations respectively as OR ≥ 1.177, p-value ≤ 0.028, ß ≥ -0.62 and r  ≥ -0.31. CONCLUSION: This review demonstrated a statistically significant association between polypharmacy and malnutrition. Further research is required to determine the magnitude of the effect by increased number of drugs in combination with the type of drugs, on the risk of malnutrition.

Skeletal Muscle Quality is Associated with Worse Survival After Pancreatoduodenectomy for Periampullary, Nonpancreatic Cancer.

BACKGROUND: Body composition measures may predict outcomes of cancer surgery. Whereas low muscle mass shown on preoperative computed tomography (CT) scans has been associated with worse outcomes after surgery for pancreatic cancer, less consideration has been given to low muscle attenuation, reflecting poor muscle quality. Studies relating muscle mass and muscle attenuation with outcomes for patients with periampullary, nonpancreatic cancer are lacking. METHODS: Skeletal muscle mass and attenuation were assessed in 166 consecutive patients undergoing pancreatoduodenectomy (PD) for periampullary, nonpancreatic cancer at a single center between 2000 and 2012. The skeletal muscle index (SMI) was calculated from cross-sectional muscle area on preoperative CT imaging at the third lumbar vertebra level (L3) and normalized for height. The skeletal muscle attenuation index (MAI) was calculated by measuring the average Hounsfield units of the total muscle area at the L3 level. Overall survival (OS) and the rate of major postoperative complications (Clavien-Dindo ≥3) were extracted from prospectively maintained databases. RESULTS: Low SMI was present in 78.3 % and low MAI in 48.8 % of the patients. The multivariate analysis showed lymph node metastasis [hazard ratio (HR) 1.8; 95 % confidence interval (CI) 1.1-2.9], microscopic radicality (HR 2.0; 95 % CI 1.2-3.4), and low MAI (HR 2.0; 95 % CI 1.2-3.3), but not low SMI to be significantly associated with decreased OS. Low MAI (HR 1.9; 95 % CI 1.0-3.8) was the only independent risk factor for major postoperative complications. CONCLUSION: Skeletal muscle quality, but not muscle mass, predicted survival and major complications after PD for periampullary, nonpancreatic cancer. Preoperative CT-derived body composition measures may stratify patients into risk categories and support shared decision making.

Bioelectrical impedance analysis to estimate body composition in surgical and oncological patients: a systematic review.

OBJECTIVE: Bioelectrical impedance analysis (BIA) is a commonly used method for the evaluation of body composition. However, BIA estimations are subject to uncertainties.The aim of this systematic review was to explore the variability of empirical prediction equations used in BIA estimations and to evaluate the validity of BIA estimations in adult surgical and oncological patients. SUBJECTS: Studies developing new empirical prediction equations and studies evaluating the validity of BIA estimations compared with a reference method were included. Only studies using BIA devices measuring the entire body were included. Studies that included patients with altered body composition or a disturbed fluid balance and studies written in languages other than English were excluded.To illustrate variability between equations, fixed normal reference values of resistance values were entered into the existing empirical prediction equations of the included studies and the results were plotted in figures. The validity was expressed by the difference in means between BIA estimates and the reference method, and relative difference in %. RESULTS: Substantial variability between equations for groups (including men and women) was found for total body water (TBW) and fat free mass (FFM). The gender-specific existing general equations assume less variability for TBW and FFM. BIA mainly underestimated TBW (range relative difference -18.8% to +7.2%) and FFM (range relative differences -15.2% to +3.8%). Estimates of the fat mass (FM) demonstrated large variability (range relative difference -15.7 to +43.1%). CONCLUSIONS: Application of equations validated in healthy subjects to predict body composition performs less well in oncologic and surgical patients. We suggest that BIA estimations, irrespective of the device, can only be useful when performed longitudinally and under the same standard conditions.

Presence and persistence of nutrition-related symptoms during the first year following esophagectomy with gastric tube reconstruction in clinically disease-free patients.

BACKGROUND: Esophagectomy with gastric tube reconstruction results in a variety of postoperative nutrition-related symptoms that may influence the patient's nutritional status. METHODS: We developed a 15-item questionnaire, focusing on the nutrition-related complaints the first year after an esophagectomy. The questionnaire was filled out the first week after discharge and 3, 6, and 12 months after surgery. The use of enteral nutrition, meal size and frequency, social aspects related to eating, defecation pattern, and body weight were recorded at the same time points. We analyzed the relationship between the baseline characteristics and the number of nutrition-related symptoms, as well as the relationship between those symptoms and body weight with linear mixed models. RESULTS: We found no significant within-patient change for the total number of nutrition-related symptoms (P = 0.67). None of the baseline factors were identified as predictors of the complaint scores. The most frequently experienced complaints were early satiety, postprandial dumping syndrome, inhibited passage due to high viscosity, reflux, and absence of hunger. One year after surgery, meal sizes were still smaller, the social aspects of eating were influenced negatively, and patients experienced an altered stool frequency. Directly after the surgical procedure 78% of the patients lost weight, and the entire postoperative year the mean body weight remained lower (P = 0.47). We observed no association between the complaint scores and body weight (P = 0.15). CONCLUSIONS: After an esophagectomy, most patients struggle with nutrition-related symptoms, are confronted with nutrition-related adjustments and a reduced body weight.

Effect of dehydroepiandrosterone supplementation on fatty acid and hormone levels in patients with X-linked adrenoleucodystrophy.

OBJECTIVE: In X-linked adrenoleucodystrophy (X-ALD) the peroxisomal beta-oxidation of saturated very long-chain fatty acids (VLCFAs; carbon length > 22 atoms) is impaired. These fatty acids accumulate in blood and tissues, in particular in the nervous system, adrenal cortex and testis. Most patients have a primary adrenocortical insufficiency with low levels of cortisol and dehydroepiandrosterone (DHEA) and its sulphate ester (DHEA-S), collectively called DHEA(S). Surprisingly, very low plasma levels of DHEA(S) may be found when plasma cortisol and ACTH levels are normal. In animal studies DHEA administration had a peroxisome proliferating effect and induced the expression of peroxisomal enzymes involved in the beta-oxidation of fatty acids. PATIENTS AND DESIGN: To study the effect of DHEA on fatty acids in X-ALD patients, we conducted a randomized double-blind study in which 14 men (age range 21-63 years) and one boy (12 years) received 50 mg of DHEA or placebo for 3 months, followed by a 1-month wash-out period, then 3 months of placebo or vice versa. RESULTS: A significant rise was seen in the plasma levels of DHEA-S, Delta4-androstenedione and IGF-I. The elevated saturated VLCFAs in plasma and erythrocytes did not change. However, in erythrocytes significant decreases were found in the total amount of fatty acids, in C16:0, C18:0 and in C20:4omega-6, C22:5omega-6, C18:1omega-9, C20:1omega-9 and C20:3omega-9. In plasma, decreases were found for C18:1omega-9 and increases for C20:1omega-9. CONCLUSIONS: Dehydroepiandrosterone supplementation for 3 months did not lower the elevated plasma levels of saturated very long-chain fatty acids in patients with X-linked adrenoleucodystrophy. Instead, a decrease in saturated and mono- and polyunsaturated fatty acids in erythrocytes and plasma was found. An increase of C20:1omega-9 was found in plasma only.

Progression of abnormalities in adrenomyeloneuropathy and neurologically asymptomatic X-linked adrenoleukodystrophy despite treatment with "Lorenzo's oil".

OBJECTIVES: X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder of peroxisomal fatty acid oxidation, biochemically characterised by the accumulation of saturated very long chain fatty acids (VLCFAs), particularly hexacosanoic acid (C26:0). Dietary treatment with a 4:1 mixture of glyceroltrioleate and glyceroltrierucate ("Lorenzo's oil") normalises plasma VLCFA concentrations, but neither ameliorates nor arrests the rapid progression of neurological symptoms in the cerebral variants of X-ALD. The efficacy of "Lorenzo's oil" in the milder phenotypes of X-ALD was assessed, as this has been much less investigated. METHODS: Twenty two patients who were treated with "Lorenzo's oil" for at least 12 months for a median period of 2.5 (range 1.0-6.0) years were studied. Two had asymptomatic ALD, four the "Addison only" variant, 13 adrenomyeloneuropathy (AMN), and three were symptomatic female carriers. RESULTS: The plasma C26:0 concentration normalised or near normalised in 19 patients (86%), in the three others it decreased significantly. Nevertheless, disability as measured with the extended disability status scale score increased mildly (0.5 (95% confidence interval (95% CI) 0.25-1.0)) in the 16 patients with neurological symptoms. Furthermore, one "Addison only" patient and one patient with AMN developed cerebral demyelination, and another "Addison only" patient developed AMN. Adrenocortical insufficiency evolved in one patient with AMN, and hypogonadism in one patient with asymptomatic ALD and two patients with AMN. Nerve conduction, evoked potential studies (SEP, BAEP, VEP), and abnormalities on cerebral MRI did not improve. On the other hand, side effects were often noted-namely, mild increases in liver enzymes (55%), thrombocytopenia (55%), gastrointestinal complaints (14%), and gingivitis (14%). We also found a mild decrease in haemoglobin concentration and leucocyte count. CONCLUSIONS: The data suggest that treatment with "Lorenzo's oil" neither improved neurological or endocrine function nor arrested progression of the disease. Furthermore, the oil often induced adverse effects. Therefore, it is advocated that "Lorenzo's oil" should not be prescribed routinely to patients with X-ALD who already have neurological deficits.

Placebo controlled trial of enteric coated pancreatin microsphere treatment in patients with unresectable cancer of the pancreatic head region.

BACKGROUND: Impeded flow of pancreatic juice due to mechanical obstruction of the pancreatic duct in patients with cancer of the pancreatic head region causes exocrine pancreatic insufficiency with steatorrhoea and creatorrhoea. This may contribute to the profound weight loss that often occurs in these patients. AIMS: To investigate whether pancreatic enzyme replacement therapy prevents this weight loss. PATIENTS: Twenty one patients with unresectable cancer of the pancreatic head region with suspected pancreatic duct obstruction, a biliary endoprosthesis in situ, and a Karnofsky performance status greater than 60. METHODS: Randomised double blind trial of eight weeks with either placebo or high dose enteric coated pancreatin enzyme supplementation. All patients received dietary counselling. RESULTS: The mean difference in the percentage change of body weight was 4.9% (p = 0.02, 95% confidence interval for the difference: 0.9 to 8.9). Patients on pancreatic enzymes gained 1.2% (0.7 kg) body weight whereas patients on placebo lost 3.7% (2.2 kg). The fat absorption coefficient in patients on pancreatic enzymes improved by 12% whereas in placebo patients it dropped by 8% (p = 0.13, 95% confidence interval for the difference: -6 to 45). The daily total energy intake was 8.42 MJ in patients on pancreatic enzymes and 6.66 MJ in placebo patients (p = 0.04, 95% confidence interval for the difference: 0.08 to 3.44). CONCLUSIONS: Weight loss in patients with unresectable cancer of the pancreatic head region and occlusion of the pancreatic duct can be prevented, at least for the period immediately after insertion of a biliary endoprosthesis, by high dose enteric coated pancreatin enzyme supplementation in combination with dietary counselling.

Maldigestion associated with exocrine pancreatic insufficiency: implications of gastrointestinal physiology and properties of enzyme preparations for a cause-related and patient-tailored treatment.

Clinical conditions in which secondary maldigestion associated with exocrine pancreatic insufficiency occur include chronic pancreatitis, cystic fibrosis, pancreatic cancer, partial or total gastrectomy, and pancreatic resection. Maldigestion can cause serious weight loss, nutritional deficiencies, and subjective complaints associated with steatorrhea. The various causes of exocrine pancreatic insufficiency may be associated with cause-related changes in gastrointestinal physiology, such as changes in gastrointestinal intraluminal pH, bile acid metabolism, gastric emptying, and intestinal motility. Therefore, to optimize the efficacy of treatment, the management of exocrine pancreatic insufficiency must be individually tailored to account for both the underlying cause and any associated disturbance in gastrointestinal physiology. In addition, the properties of the pancreatic enzyme preparations and adjuvant drugs need to be taken into consideration. This paper reviews the pathophysiological mechanisms of maldigestion in exocrine pancreatic insufficiency, discusses the efficacy of different therapy regimens, and gives guidelines for a cause-related and patient-tailored treatment with respect to both drug therapy and dietary counselling.

Delay in diagnosis of X-linked adrenoleukodystrophy.

In 16 consecutive patients with clinically suspected and biochemically proven X-linked adrenoleukodystrophy (X-ALD), total delay (interval between onset of symptoms and diagnosis) and specialist delay (interval between referral to a specialist and diagnosis) were determined. All patients previously were unaware of the existence of X-ALD in their families. From the time of onset of symptoms attributable to this disease until diagnosis, mean total delay was 9.9 (range 1-33) years and mean specialist delay was 8.4 (range 0-33) years. Three patients who presented with adrenocortical insufficiency had mean total and specialist delays of 17.3 (range 9-33) years. Five patients with an initial diagnosis of multiple sclerosis had mean total and specialist delays of 12.8 (range 5-25) and 11.2 (range 1-23) years, respectively. In 12 patients with adrenomyeloneuropathy--the second most frequent phenotype of X-ALD--mean total delay was 11.0 (range 2-33) years and mean specialist delay 9.1 (range 0-33) years. Since 1981 X-ALD can be reliably diagnosed on the basis of elevated levels of very long chain fatty acids in plasma and/or cultured fibroblasts. The delays therefore must have been due to the unfamiliarity with the clinical manifestations and diagnostic possibilities of this disease. Once X-ALD is diagnosed, dietary treatment and/or bone marrow transplantation may be considered. Genetic counseling should be performed, and screening of other family members is essential for the early identification of affected relatives.