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.

Simultaneous islet-kidney vs pancreas-kidney transplantation in type 1 diabetes mellitus: a 5 year single centre follow-up.

AIMS/HYPOTHESIS: The aim of this study was to compare the long-term outcomes--in terms of glucose control, renal function and procedure-related complications--of simultaneous islet-kidney (SIK) transplantation with those of simultaneous pancreas-kidney (SPK) transplantation in patients with type 1 diabetes mellitus. METHODS: HbA1c, need for insulin, GFR and complication rate were compared between 13 recipients of SIK and 25 recipients of SPK transplants at the same institution. The mean follow-up was 41 months. RESULTS: Two primary organ non-functions occurred in the SIK group. HbA1c did not differ at any time point during follow-up in the SIK group compared with the SPK group (mean during follow-up 6.3 vs 5.9%). Similarly, kidney function over time was not different between the two groups. A higher rate of insulin independence following SPK transplantation (after 1 year 96 vs 31% in the SIK group) was counterbalanced by a higher rate of serious adverse events (40% relaparotomies vs 0% in the SIK group). CONCLUSIONS/INTERPRETATION: The endogenous insulin production achieved by islet transplantation, combined with optimal insulin therapy, was sufficient for maintaining near-normal glucose levels. In terms of glucose control, islet transplantation provides results comparable to those achieved with pancreas transplantation. However, SPK results in a higher rate of insulin independence, albeit at the cost of more surgical complications. These results have led to a new paradigm in islet transplantation at our institution, where the primary goal is not insulin independence, but good glucose control and avoidance of severe hypoglycaemia.

Inaccurate self-monitoring of blood glucose readings in patients on chronic ambulatory peritoneal dialysis with icodextrin.

Patients on chronic ambulant peritoneal dialysis (CAPD) are increasingly likely to be treated with a new solution of corn starch-derived glucose polymers called icodextrin. This solution involves a very low carbohydrate absorption leading to a better glycemic control in diabetic patients. However these glucose polymers pass to the blood and are metabolized to oligosaccharids which interfere with blood glucose in distinct capillary glucose analyzers leading to overestimation of glycemia. We assessed the accuracy of glucose measurements with the three most commonly used glucose analyzers compared to venous plasma glucose measurement at our institution in 8 patients (4 patients with type 2 diabetes) on CAPD using icodextrin. Glycemia was measured simultaneously in plasma of venous blood using a reference laboratory method and in capillary blood using Accu-Chek sensor (Rotkreuz, Switzerland) (glucose dehydrogenase method), Glucotrend 2 (Rotkreuz, Switzerland) (glucose-dye-oxyreductase method) and Ascensia elite (Zurich, Switzerland) (glucose oxidase method) glucose analyzers. Only glucose readings with Ascensia elite correspond correctly with venous plasma glucose results (+0.3 mmol/l; n. s.), whereas glycemia was significantly overestimated by Accu-Chek sensor (+4.3 mmol/l; p<0.0001) and Glucotrend 2 glucose analyzers (+3.7 mmol/l; p<0.0001). Thus we conclude that distinct glucose analyzers overestimate real blood glucose concentration and are not suitable for monitoring glycemia in patients on CAPD with icodextrin. On the basis of our results, these patients should use glucose analyzers using glucose oxidase methods. All glucose analyzers should be cross-checked with a laboratory reference method before the application in patients on CAPD with icodextrin is recommended.

Thyrotoxicosis-induced prinzmetal variant angina.

We describe a postmenopausal women with new onset of variant angina caused by thyrotoxicosis due to Graves' disease. During exercise bicycle ergometry at 50 Watts, the patient developed typical angina with ST segment elevation in the precordial leads. A coronary angiogram revealed normal coronary arteries. Graves' disease with overt hyperthyroidism was diagnosed. After achieving an euthyroid state with administration of propylthiouracil, the symptoms resolved completely and the patient had a normal exercise capacity without electrocardiographic changes. Thus, we conclude that in patients with thyrotoxicosis, variant angina and normal coronary arteries, restoration of normal thyroid function may be curative.

[Islet transplantation in type I diabetes mellitus]. / Inseltransplantation bei Typ I Diabetes mellitus.

Type 1 diabetes mellitus results from autoimmune destruction of the insulin-secreting cells in the pancreas. The dramatic breakthrough in 2000 with the "Edmonton protocol" for successful solitary islet transplantation has restored optimism for the application of islet transplantation as a treatment for type I diabetes. Due to the recent successes, islet transplantation has evolved from a theoretical concept to its current status as a therapeutic option for patients with type 1 diabetes. Islet transplantation has shown to normalize metabolic control in a way that has been virtually impossible to achieve with exogenous insulin. The less invasive procedure of islet transplantation as compared to whole pancreas transplantation in patients with type 1 diabetes mellitus would be expected to be safer and much less costly. However, this procedure also requires lifetime immunosuppression with drugs. The limited availability of donor organs and the necessity of transplantation of several pancreata in order to achieve insulin independence limit this procedure to a small minority of patients. Unlike the North American centers, the European centers concentrated their efforts on islet after kidney and simultaneous islet kidney transplantation. The two Swiss islet transplantation programs have been pioneers in applying the steroid-free "Edmonton protocol" to simultaneous islet-kidney and islet after kidney transplantation. The long term follow-up showed that islet function decreases over time. In order to maintain insulin independence repeated islet transplants would have to be given to the patients. Therefore, there has been a change in paradigm over time. The major goal of islet transplantation focuses now on achieving a good blood glucose control and avoidance of severe hypoglycaemic episodes rather than only insulin-independence. Thus, due to the limited supply of donor organs, more patients can benefit from islet transplantation. Small insulin doses of exogenous insulin prevent stress on the islet in particular after meals and might help to maintain the transplanted islet mass over time. Due to the severe limitations of immunosuppression solitary islet transplantation is limited to a very small number of patients with type 1 diabetes. The most common indication for islet transplantation in Switzerland is terminal kidney failure in patients with type I diabetes. A simultaneous islet-kidney or pancreas-kidney transplantation should be offered to these patients. The choice between islet or pancreas transplantation is a matter of age and diabetic complications because the perioperative risk is considerably higher in pancreas transplantation.

Increased myocardial blood flow during acute exposure to simulated altitudes.

BACKGROUND: Although only poor data exist on changes in myocardial blood flow (MBF) under acute hypoxia, patients with known coronary artery disease are advised not to exceed a moderate altitude exposure of about 2000 m above sea level. METHODS AND RESULTS: We measured MBF with positron emission tomography using O-15--labeled water in 8 healthy human volunteers (aged 26 +/- 3 years [mean +/- SD]) at baseline (450 m above sea level, Zurich, Switzerland) and during acute hypoxic hypoxemia induced by inhalation of 2 hypoxic gas mixtures corresponding to altitudes of 2000 and 4500 m. MBF remained unchanged at 2000 m (increase of 10%, not significant) but increased significantly at 4500 m (62%, P <.001), exceeding the relative increase in rate pressure product. CONCLUSIONS: Our results may explain why exposure to an altitude of 2000 m (corresponding to the cabin pressure in most airplanes during flight) is clinically well tolerated, even by patients with reduced coronary flow reserve, such as those with coronary artery disease. However, at an altitude of 4500 m, MBF increases significantly, supporting the recommendation that patients with impaired flow reserve avoid exposure to higher altitudes.

Effects of hypobaric hypoxia on vascular endothelial growth factor and the acute phase response in subjects who are susceptible to high-altitude pulmonary oedema.

In order to investigate whether vascular endothelial growth factor (VEGF) and inflammatory pathways are activated during acute hypobaric hypoxia in subjects who are susceptible to high-altitude pulmonary oedema (HAPE-S), seven HAPE-S and five control subjects were exposed to simulated altitude corresponding to 4000 m in a hypobaric chamber for 1 day. Peripheral venous blood was taken at 450 m (Zürich level) and at 4000 m, and levels of erythropoietin (EPO), VEGF, interleukin-6 (IL-6) and the acute-phase proteins complement C3 (C3), alpha1-antitrypsin (alpha1AT), transferrin (Tf) and C-reactive protein (CRP) were measured. Peripheral arterial oxygen saturation (SaO2) was recorded. Chest radiography was performed before and immediately after the experiment. EPO increased during altitude exposure, correlating with SaO2, in both groups (r = -0.86, P < 0.001). Venous serum VEGF did not show any elevation despite a marked decrease in SaO2 in the HAPE-S subjects [mean (SD) HAPE-S: 69.6 (9.1)%; controls: 78.7 (5.2)%]. C3 and alpha1AT levels increased in HAPE-S during hypobaric hypoxia [from 0.94 (0.11) g/l to 1.07 (0.13) g/l, and from 1.16 (0.08) g/l to 1.49 (0.27) g/l, respectively; P < 0.05], but remained within the clinical reference ranges. No significant elevations of IL-6, Tf or CRP were observed in either group. The post-exposure chest radiography revealed no signs of oedema. We conclude that VEGF is not up-regulated in HAPE-S and thus does not seem to increase critically pulmonary vascular permeability during the 1st day at high altitude. Furthermore, our data provide evidence against a clinically relevant inflammation in the initial phase of exposure to hypoxia in HAPE-S, although C3 and alpha1AT are mildly induced.

[Effects of carvedilol, a sympatholytic, in experimental alloxan diabetes in laboratory rats]. / Studium úcinku sympatolytika carvedilolu v podmínkách experimentálního alloxanového diabetu u laboratorního potkana.

A possible effect of the sympatholytic carvedilol on alloxan-induced diabetes mellitus in the laboratory rat was examined in experiments. The animals were divided into a group treated with carvedilol in a single daily dose of 10mg/kg in 1 ml of diluting solution i.p and the control group which received only diluting solution in the pertinent amount. The values of malondialdehyde and glucose in the serum, diuresis and total losses of sugar in the urine within 24 hours were estimated and histopathological examination of the kidneys of the treated and control groups was performed. The results show an effect of the tested dose of the drug, primarily in the region the proximal renal tubule.

Changes of cerebral blood flow during short-term exposure to normobaric hypoxia.

Decreased arterial partial oxygen pressure (PaO2) below a certain level presents a strong stimulus for increasing cerebral blood flow. Although several field studies examined the time course of global cerebral blood flow (gCBF) changes during hypoxia at high altitude, little was known about the regional differences in the flow pattern. Positron emission tomography (PET) with [(15)O]H2O was used on eight healthy volunteers to assess regional cerebral blood flow (rCBF) during short-term exposure to hypoxia corresponding to simulated altitudes of 3,000 and 4,500 m. Scans at the simulated altitudes were preceded and followed by baseline scans at the altitude of Zurich (450 m, baseline-1 and baseline-2). Each altitude stage lasted 20 minutes. From baseline to 4,500 m, gCBF increased from 34.4 +/- 5.9 to 41.6 +/- 9.0 mL x minute(-1) x 100 g(-1) (mean +/- SD), whereas no significant change was noted at 3,000 m. During baseline-2 the flow values returned to those of baseline-1. Statistical parametric mapping identified the hypothalamus as the only region with excessively increased blood flow at 4,500 m (+32.8% +/- 21.9% relative to baseline-1). The corresponding value for the thalamus, the structure with the second largest increase, was 19.2% +/- 16.3%. Compared with the rest of the brain, an excessive increase of blood flow during acute exposure to hypoxia is found in the hypothalamus. The functional implications are at present unclear. Further studies of this finding should elucidate its meaning and especially focus on a potential association with the symptoms of acute mountain sickness.

[The effects of Carvedilol, a beta-blocker, in experimental ischemia-reperfusion kidney injury]. / Studium úcinku beta-blokátoru Carvedilolu pri ischemicko-reperfuzním poskození ledviny v experimentu.

Carvedilol is a recently introduced drug with multiple action with a non-selective beta-antiadrenergic and selective alpha1-antiadrenergic action used for treatment of mild to medium severe hypertension. The authors investigated in their experiments the protective effect of carvedilol under conditions of ischaemia-reperfusion of the kidney in the laboratory rat. The animals were divided into four groups 1. the control group was fed a diet without carvedilol for a period of two weeks. Groups 2, 3 and 4 were fed for two weeks a diet containing carvedilol, 1-3-10 mg/kg/day resp. After completed medication in all animals ischaemia of the kidney was induced (60 min.) with subsequent reperfusion (10 min.) Then the animals were sacrificed, the kidney was removed for histopathological examination, in blood the malondialdehyde (MDA) level was assessed. The conclusions of the investigation indicate a marked protective effect of the administered preparation. Carvedilol prevents the disintegration of tubular epithelia, pycnosis of the nuclei, and reduced the development of oedematous changes. These findings correlate with MDA levels.

[Extracorporeal membrane oxygenation. Initial experience at an ECMO center. 1]. / Extracorporeal membrane oxygenation (ECMO). První zkusenosti ECMO centra (1. cást).

The authors describe their initial experience, organization, and problems associated with the development of an EMCO centre. Its main activities are those of a neonatal ECMO centre (to a smaller extent paediatric ECMO and ECCO2R-LF PPV of adults) during the first 4 months of its existence. During the period the ECMO centre was contacted in 10 instances. The referring department indicated the ECMO centre correctly in six instances. However, at least in two instances too late and the patients died (during priming of the ECMO circuit or transport could not be implemented because of the critical condition). In two instances, however, the ECMO staff failed as it was unable to ensure a minimum of seven days of safe operation of ECMO and therefore ECMO was not provided. Based on this experience the authors present an organizational model of the ECMO unit which is formed ad hoc when needed and comprises specialists of various professions from the sphere of emergency medicine. The main purpose of the present paper is to inform referring departments on the indications, selection criteria, contraindications of ECMO in neonates and children and to ensure thus not only smooth communication between the ECMO centre and the referring department but in the first place early referral to the ECMO centre at a time when transport is not yet a problem.

Human neutrophil mobilization during open heart surgery.

Phagocyte released reactive oxygen species are often discussed in connection with ischemic and reperfusion injuries to the myocardium. The kinetics of the accumulation and oxidative burst of human blood phagocytes was studied by chemiluminescence during open heart surgery in the myocardium of human patients. Direct evidence is presented for an accumulation of neutrophils along with their markedly increased metabolic activity (oxygen radical formation), especially following the reperfusion of the ischemic myocardium. Leukocyte numbers and activity remained significantly elevated even in the venous blood obtained 24 h after the operation.

Surgical aspects of the implantation of a left ventricle assist device.

The authors have summarised their experience with short-term use of a left ventricle assist device (LVAD). Nine experiments were carried out in healthy calves. A polyurethane pump of their own design, placed extracorporeally, was used. Its in-flow cannula was placed in the left atrium, the outflow one in the initial segment of the descending aorta. The LVAD was operated for a period of 5 days. Fourteen days after its disconnection, the animal was sacrificed and both the bypass system and parenchymal organs were examined. No surgical complications were observed during the experiments. Macro- and microscopical pictures showed minor infarctions in the renal tissue which, however, did not impair renal function. The findings in other organs were related to anaesthesia, the operative procedure and way of animal sacrificing. The experiments have proved the safety of the bypass system used over a short period and, consequently, its potential for future clinical application.

Hematological and biochemical studies in calves living over 100 days with the polymethylmethacrylate total artificial heart TNS Brno II.

A polymethylmethacrylate total artificial heart (kinetic components made of polyetherurethane) of TNS Brno II type was implanted into seven calves (2-5 months of age) surviving for the average of 152.4 +/- 19.1 days after the implantation. During the entire post-operative period the animals received oral warfarin-sodium, acetylsalicylic acid, dipyridamole and alpha-tocopherol. Blood was taken for biochemical and hematological examinations twice a week from the jugular vein. During the experiments there were decreases in the number of red blood cells, hematocrit and hemoglobin levels. Plasma free hemoglobin and serum enzymes (alkaline phosphatase, AST, ALT, LDH) increased. Coagulation tests were abnormal because anticoagulation therapy was used. There were minimal changes in the number of white blood cells and platelets, fibrinogen, blood pH, blood glucose, serum electrolytes, bilirubin (total and direct), creatinine, blood urea, and lactate. Possible reasons for observed changes include the gradual rise in the central venous pressure and damaged function of the liver parenchyma. Other factors playing a possible role in inducing changes in laboratory findings are also discussed.

A comparative study of a group of eight calves, surviving longer than 1 month with the total artificial heart.

Over the last 2 1/2 years, eight calves with implanted total artificial hearts (from experimental group IV) have survived for greater than 1 month. In this group two subgroups were further differentiated, subgroup IVa, including three calves surviving 31, 35, and 75 days, and subgroup IVb, with five calves surviving 104, 142, 150, and 155 days and one calf still surviving greater than 160 days. Mean survival in the fourth group was greater than 106.5 days. The artificial ventricles used were the TNS-BRNO-II made of polymethylmethacrylate (seven calves) and the TNS-BRNO-III, made of segmented polyetherurethane (one calf). The controller and driving units were of our own design. The Chirasist-TN-3 and TN-4 worked without trouble over the total duration of the studies in all calves. Autoregulation of suction was used in three of these calves. All calves survived in good physiological condition; however, some common changes were observed in all of them, such as a gradual central venous pressure increase and liver enlargement. Anticoagulation therapy was used in all calves. Causes of death were technical in three cases and biological in four. Body weight gains were normal in the majority of these calves, with slight individual differences observed. Diaphragm mineralization of various degrees was observed in three cases. In one of them it was directly related to the cause of death. These results are very encouraging for further development of the total artificial heart research in our center.

Some problems associated with the implantation of a cardiac prosthesis and with early postoperative care in animals with a total artificial heart.

The progress in the methods and techniques for surgical implantation of the TAH has progressed in parallel with the technology and design of the cardiac prosthesis. During the period from December 1974 to May 1982 the authors performed altogether 75 orthotopic implantations of eight types of TAH in calves. The Soviet TAH type KEDR I-III was implanted in 26 calves, type MODUL to one calf. The American TAH JARVIK 3 was implanted in one calf and Czechoslovak TAH type TNS BRNO I-III in 47 calves. The modification of blood pump and improved system of its control provided for the limitation of the range of surgery and to shorten the time of operation and cardiopulmonary bypass. The methods of preoperative care, anaesthesia, cardiopulmonary bypass and postoperative care in our laboratory were gradually improving in parallel. This was associated with maximum survival time of animals in the course of the research period which gradually increased from 5.5 h in 1974 to 173 days in 1982. The chief experiences acquired from all experiments performed are presented and problems associated with the investigation of the TAH in general are discussed in this paper.