Nutritional support during the hospital stay reduces mortality in patients with different types of cancers: secondary analysis of a prospective randomized trial.

BACKGROUND: Nutritional support in patients with cancer aims at improving quality of life. Whether use of nutritional support is also effective in improving clinical outcomes requires further study. PATIENTS AND METHODS: In this preplanned secondary analysis of patients with cancer included in a prospective, randomized-controlled, Swiss, multicenter trial (EFFORT), we compared protocol-guided individualized nutritional support (intervention group) to standard hospital food (control group) regarding mortality at 30-day (primary endpoint) and other clinical outcomes. RESULTS: We analyzed 506 patients with a main admission diagnosis of cancer, including lung cancer (n = 113), gastrointestinal tumors (n = 84), hematological malignancies (n = 108) and other types of cancer (n = 201). Nutritional risk based on Nutritional Risk Screening (NRS 2002) was an independent predictor for mortality over 180 days with an (age-, sex-, center-, type of cancer-, tumor activity- and treatment-) adjusted hazard ratio of 1.29 (95% CI 1.09-1.54; P = 0.004) per point increase in NRS. In the 30-day follow-up period, 50 patients (19.9%) died in the control group compared to 36 (14.1%) in the intervention group resulting in an adjusted odds ratio of 0.57 (95% CI 0.35-0.94; P = 0.027). Interaction tests did not show significant differences in mortality across the cancer type subgroups. Nutritional support also significantly improved functional outcomes and quality of life measures. CONCLUSIONS: Compared to usual hospital nutrition without nutrition support, individualized nutritional support reduced the risk of mortality and improved functional and quality of life outcomes in cancer patients with increased nutritional risk. These data further support the inclusion of nutritional care in cancer management guidelines.

A 37-year-old Menkes disease patient-Residual ATP7A activity and early copper administration as key factors in beneficial treatment.

Menkes disease (MD) is a lethal disorder characterized by severe neurological symptoms and connective tissue abnormalities; and results from malfunctioning of cuproenzymes, which cannot receive copper due to a defective intracellular copper transporting protein, ATP7A. Early parenteral copper-histidine supplementation may modify disease progression substantially but beneficial effects of long-term treatment have been recorded in only a few patients. Here we report on the eldest surviving MD patient (37 years) receiving early-onset and long-term copper treatment. He has few neurological symptoms without connective tissue disturbances; and a missense ATP7A variant, p.(Pro852Leu), which results in impaired protein trafficking while the copper transport function is spared. These findings suggest that some cuproenzymes maintain their function when sufficient copper is provided to the cells; and underline the importance of early initiated copper treatment, efficiency of which is likely to be dependent on the mutant ATP7A function.

Relationship between HbA1c on target, risk of silent hypoglycemia and glycemic variability in patients with type 2 diabetes mellitus.

OBJECTIVE: We aimed to compare time spent at low glucose level (silent hypoglycemia, glucose <3.0 mmol/l) and glycemic variability in patients who reached HbA1c <7.0% with those who did not. RESEARCH DESIGN AND METHODS: In 108 type 2 diabetic patients the interstitial glucose concentration was measured with CGMS (Continuous Glucose Monitoring System) over 72 h. Patients were divided in group 1 with an HbA1c <7.0% (n=63) and group 2 with an HbA1c≥7.0% (n=45). RESULTS: 24% in group 1 experienced silent hypoglycemia vs. 11% in group 2 (n. s.), duration of silent hypoglycemia over 48 h was 27±71 min vs. 7±36 min (n. s.). This was also valid for the subgroups treated with insulin. Patients in group 2 had a significantly higher standard deviation of average glucose (2.3±0.8 vs. 1.3±0.6; p<0.001) and MAGE (mean amplitude of glycemic excursions) (4.8±2.1 vs. 2.6±1.1; p<0.001). CONCLUSION: Silent hypoglycemia tended to occur more often and to last longer in patients with HbA1c <7%. However, patients with HbA1c >7% had a higher glycemic variability. HbA1c >7% wasn't a reliable indicator of lower risk of hypoglycemia.

[Craniopharyngioma--a "geographical malignant" tumour]. / Das Kraniopharyngeom--ein "geographisch maligner" Tumor.

The craniopharyngioma is a rare dysontogenetic tumour that originates from either scattered cells of the craniopharyngeal duct or from metaplastically mutated anterior pituitary parenchyma cells. Despite being classified as a WHO-Class-I tumour, the histologically benign craniopharyngioma may display an aggressive behaviour. Like other congenital tumours, it usually becomes manifest within the first two decades of life. Patients typically complain of headache and a chiasma syndrome with bitemporal hemianopsy may develop depending on tumour localisation. In children, anterior pituitary insufficiency often manifests as growth restriction. Additionally, diabetes insipidus and other hormonal disturbances may develop. Therapeutically either radical total removal or subtotal resection in combination with postoperative radiation is recommended. In cystic tumors, stereotactic cyst drainage and adjuvant radiation may be a possible alternative. The prognosis is best in patients who are diagnosed early.

[Hypertension and hyperhidrosis. Pheochromocytoma]. / Hypertonie und Schwitzen. Phaochromozytom.

A 39-year-old woman was referred to our hypertension clinic with refractory hypertension. The patient history gave certain clues for pheochromocytoma. The diagnosis was proven with elevated metanephrines and computer tomography. The tumor was surgically removed.

Women with polycystic ovary syndrome are sensitive to the TNF-alpha-lowering effect of glucose-induced hyperinsulinaemia.

BACKGROUND: Restoration of near-euglycaemia by intensive insulin therapy results in decreased serum levels of inflammatory mediators. The authors investigated whether the anti-inflammatory effect of insulin was independent of its glucose-lowering action and if this effect was intact in insulin-resistant women with the polycystic ovary syndrome (PCOS) characterized by low-grade chronic inflammation. MATERIALS AND METHODS: Blood was drawn on the third and sixth days after progestin-induced withdrawal bleeding in 20 young non-diabetic women with PCOS and once between the third and sixth days of the menstrual cycle in 21 age-matched lean healthy control women during a 75-g oral glucose tolerance test (oGTT). Serum insulin, glucose and tumour necrosis factor alpha (TNF-alpha) concentrations were measured after 0, 30, 60, 90 and 120 min. RESULTS: The increase in insulin and glucose concentrations during the oGTT was significantly more pronounced in patients with PCOS (one patient with impaired fasting glucose, one patient with impaired glucose tolerance, three patients with both) compared with healthy controls. The TNF-alpha serum concentrations decreased in patients with PCOS (mean of both days, P = 0.004). In patients and in controls, there was an inverse correlation between the serum concentrations of insulin and of TNF-alpha during oGTT (for patients, a mean of both days, P = 0.009; for controls, P = 0.047), but not between the serum concentrations of glucose and TNF-alpha. CONCLUSIONS: The decrease in TNF-alpha concentrations during oGTT and the inverse correlation between endogenous hyperinsulinaemia and serum TNF-alpha concentrations suggested an anti-inflammatory effect of moderately-high insulin concentrations. This occurred despite the presence of moderate hyperglycaemia. These findings also demonstrated a preserved responsiveness of inflammatory mediators to insulin in PCOS.

Changes in bone mineral content after surgical treatment of morbid obesity.

Weight loss reduces bone mass and increases the risk of osteoporosis. This study was undertaken to assess changes of bone metabolism following Roux-en-Y gastric bypass (RYGB) and adjustable silicone gastric banding (ASGB) as compared to nonoperated controls of morbidly obese subjects. Fourteen female and 5 male patients with a mean (+/-SEM) age of 44.3 +/- 1.8 years participated in the 24-month prospective study. Nine patients underwent ASGB, 4 patients RYGB operation, and 6 patients were included in the control group. Bone metabolism was assessed by determination of serum parathyroid hormone (PTH), osteocalcin, urinary deoxypyridinoline, and dual energy x-ray absorptiometry (DXA) before, and 6, 12, and 24 months after intervention. The body mass index (BMI) decreased from 41.0 +/- 1.1 to 34.0 +/- 1.4 kg/m2 in the ASGB group (P = .001), from 42.7 +/- 2.2 to 30.5 +/- 2.2 kg/m2 in the RYGB group (P = .006), and remained unchanged in the control group (from 41.2 +/- 1.2 to 41.4 +/- 1.4 kg/m2) after 24 months. Bone mineral content (BMC) showed no significant change in the ASGB group (from 3,079 +/- 140 to 3,064 +/- 129 g) and in the control group (from 2,945 +/- 130 to 2,940 +/- 111 g), whereas it decreased from 2,968 +/- 111 to 2,621 +/- 139 g in the RYGB group (P = .005). The loss in BMC was accompanied by significant increases in urinary deoxypyridinoline (P < .05) and in serum osteocalcin (P < .01) after RYGB, suggesting both, increased bone resorption and increased bone formation. The authors were aware of the fact that the study groups were small and conclusions need to be regarded as preliminary. However, the RYGB operation resulted in enhanced weight loss and significant net loss of bone mass in comparison to ASGB and obese control subjects. Patients losing large amounts of body weight should be monitored regularly regarding prevention of osteoporosis.

Effects of changes in hydration on protein, glucose and lipid metabolism in man: impact on health.

Alterations of cell volume induced by changes of extracellular osmolality have been reported to regulate intracellular metabolic pathways. Hypo-osmotic cell swelling counteracts proteolysis and glycogen breakdown in the liver, whereas hyperosmotic cell shrinkage promotes protein breakdown, glycolysis and glycogenolysis. To investigate the effect of acute changes of extracellular osmolality on whole-body protein, glucose and lipid metabolism in vivo, we studied 10 male subjects during three conditions: (i) hyperosmolality was induced by fluid restriction and intravenous infusion of hypertonic NaCl (2-5%, wt/vol) during 17 h; (ii) hypo-osmolality was produced by intravenous administration of desmopressin, liberal water drinking and infusion of hypotonic saline (0.4%); and (iii) the iso-osmolality study comprised oral water intake ad libitum. Plasma osmolality increased from 285+/-1 to 296+/-1 mosm/kg (P<0.001 during hyperosmolality, and decreased from 286+/-1 to 265+/-1 mosm/kg during hypo-osmolality (P<0.001). Total body leucine flux ([1-(13)C]leucine infusion technique), reflecting whole-body protein breakdown, as well as whole-body leucine oxidation rate (irreversible loss of amino acids) decreased significantly during hypo-osmolality. The glucose metabolic clearance rate during hyperinsulinaemic-euglycemic clamping increased significantly less during hypo-osmolality than iso-osmolality, indicating diminished peripheral insulin sensitivity. Glycerol turnover (2-[(13)C]glycerol infusion technique), reflecting whole-body lipolysis, increased significantly during hypo-osmolar conditions. The results demonstrate that the metabolic adaptation to acute hypo-osmolality resembles that of acute fasting, that is, it results in protein sparing associated with increased lipolysis, ketogenesis and lipid oxidation and impaired insulin sensitivity of glucose metabolism.

Nutritional supplements combined with dietary counselling diminish whole body protein catabolism in HIV-infected patients.

BACKGROUND: Weight loss and protein malnutrition are frequent complications in HIV-infected patients. The effect of an oral nutritional supplement combined with nutritional counselling on whole body protein metabolism was assessed. MATERIALS AND METHODS: HIV-infected individuals with a body mass index < 21 kg m-2 or CD4-T cells < 500 micro L-1 in stable clinical condition were randomly allocated to [1] receive either oral nutritional supplements (containing 2510 kJ, complete macro- and micronutrients) and dietary counselling (n = 8), or [2] identical monitoring but no supplements or specific nutritional advice (controls, n = 7). Whole body leucine kinetics and leucine oxidation rate were determined by [1-13C]-leucine infusions and lean and fat mass were measured before and 12 weeks after intervention. RESULTS: Leucine oxidation (protein catabolism) decreased in the group receiving nutritional intervention from 0.33 +/- 0.02 to 0.26 +/- 0.02 micromol kg-1 min-1 after 12 weeks (P < 0.05; P < 0.05 vs. control group) but remained unchanged in the control group. Whole body leucine flux showed a tendency to decrease in the intervention group from 1.92 +/- 0.19 to 1.73 +/- 0.14 micromol kg-1 min-1 (P = 0.07) and remained unchanged in the control group (2.21 +/- 0.16 and 2.27 +/- 0.14 micromol kg-1 min-1, respectively). Lean body mass determined by bioelectrical impedance analysis increased in the nutritional intervention group from 84 +/- 2 to 86 +/- 2 per cent (P < 0.05) and fat mass decreased from 17 +/- 2 to 14 +/- 2 per cent (P < 0.05) of total body weight whereas neither mass changed in the control group. Nutritional intervention had no significant effect on lymphocyte CD4 counts, on plasma TNFR 55, TNFR 75 and ILR 2 concentrations and on quality of life. CONCLUSIONS: The data demonstrate an anticatabolic effect of nutritional supplements combined with dietary counselling in HIV-infected subjects. They suggest that diminished whole body protein catabolism resulted in a change of body composition (increased lean mass, decreased fat mass).

[Polycystic ovary syndrome--only relevant in reproductive medicine?]. / Das Syndrom der Polycystischen Ovarien (PCOS)--nur für Kinderwunsch relevant?

The Polycystic Ovary Disease (PCOD) is one of the most common endocrine disorders in women with a prevalence of 5%. Affected women often consult a gynecologist because of menstrual irregularities, fertility problems or problems of androgen excess. However, PCOD is a metabolic disorder affecting multiple organs. Studies suggest that those women are at risk for developing several complications such as type II diabetes mellitus, hypertension, dyslipidemia and myocardial infarction. The risk to develop endometrial carcinoma is also elevated. To give adequate treatment to women with PCOD, an interdisciplinary approach of gynecologists together with endocrinologists specialized in metabolic and nutritional disorders at the University of Basel is presented. The work-up for diagnosis and assessment of risk factors is outlined. Goal of this interdisciplinary approach is an adequate evaluation of affected patients and their long-term follow-up to test if proposed interventions as weight loss, treatment of hyperinsulinemia, regulation of menstrual cycle and others can avoid long-term sequelae.

Effects of hypoosmolality on whole-body lipolysis in man.

Changes in extracellular osmolality, and thus in the cellular hydration state, appear to directly influence cell metabolism. The metabolic changes associated with cell swelling are inhibition of glycogenolysis, glycolysis, and proteolysis. Recent studies in our laboratory demonstrated diminished whole-body protein breakdown in humans during an acute hypoosmolar state. Because of the close interrelationship between carbohydrate and fat metabolism, we speculated that adipose tissue lipolysis and fatty acid oxidation are regulated by changes in extracellular osmolality. Therefore, we investigated the effect of artificially induced hypoosmolality on whole-body lipolysis and fat oxidation in seven healthy young men. Hypoosmolality was induced by intravenous administration of desmopressin, liberal ingestion of water, and infusion of hypotonic (0.45%) saline solution. Lipolysis was assessed by a stable-isotope method (2-[13C]-glycerol infusion). The glycerol rate of appearance (Ra), reflecting whole-body lipolysis, was higher under hypoosmolar compared with isoosmolar conditions (2.35+/-0.40 v 1.68+/-0.21 micromol/kg/min, P=.03). This was even more pronounced when lipolysis was suppressed during hyperinsulinemia and euglycemic clamping (0.90+/-0.08 v 0.61+/-0.03 micromol/kg/min, P=.002). However, plasma free fatty acid (FFA), glycerol, ketone body, insulin, and glucagon concentrations and carbohydrate and lipid oxidation measured by indirect calorimetry were not significantly altered by hypoosmolality. Plasma norepinephrine concentrations were lower under hypoosmolar conditions (P<.01 v control). In conclusion, hypoosmolality in vivo results in increased whole-body lipolysis, which is not due to changes in major lipolysis regulating hormones.