Publications by authors named "Bruno Schneeweiss"

29 Publications

  • Page 1 of 1

Impact of age on the cumulative risk of transformation in patients with chronic myelomonocytic leukaemia.

Eur J Haematol 2021 Aug 1;107(2):265-274. Epub 2021 Jun 1.

Department of Internal Medicine V with Hematology, Oncology and Palliative Medicine, Hospital Hietzing, Vienna, Austria.

In older patients with chronic myelomonocytic leukaemia (CMML) and limited life expectancy due to age and or comorbidities, it is particularly important to consider the risk of transformation for individualised treatment decisions. There is limited information on potential differences between younger and older CMML patients regarding the cumulative risk of transformation as well as haematological, molecular and biologic characteristics. We analysed data from the Austrian Biodatabase for CMML (ABCMML) to compare these parameters in 518 CMML patients. Categorisation of patients into 3 age-related groups: <60 years, 60-79 years and ≥80 years, showed a significantly lower risk of transformation at higher age by competing risk analysis, with a 4-year risk of 39%, 23% and 13%, respectively (P < .0001). The lower probability of transformation was associated with a lower percentage of blast cells in the peripheral blood (PB) of older patients. Furthermore, we provide a simple score based on age, PB blasts and platelet counts that allowed us to define subgroups of CMML patients with a different cumulative transformation risk, including a low-risk group with a transformation risk of only 5%. Our findings may facilitate reasonable treatment decisions in elderly patients with CMML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ejh.13647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480146PMC
August 2021

Correlation of RAS-Pathway Mutations and Spontaneous Myeloid Colony Growth with Progression and Transformation in Chronic Myelomonocytic Leukemia-A Retrospective Analysis in 337 Patients.

Int J Mol Sci 2020 Apr 24;21(8). Epub 2020 Apr 24.

Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, 1090 Vienna, Austria.

Although the RAS-pathway has been implicated as an important driver in the pathogenesis of chronic myelomonocytic leukemia (CMML) a comprehensive study including molecular and functional analyses in patients with progression and transformation has not been performed. A close correlation between RASopathy gene mutations and spontaneous in vitro myeloid colony (CFU-GM) growth in CMML has been described. Molecular and/or functional analyses were performed in three cohorts of 337 CMML patients: in patients without (A, = 236) and with (B, = 61) progression/transformation during follow-up, and in patients already transformed at the time of sampling (C, = 40 + 26 who were before in B). The frequencies of RAS-pathway mutations (variant allele frequency ≥ 20%) in cohorts A, B, and C were 30%, 47%, and 71% ( < 0.0001), and of high colony growth (≥20/10 peripheral blood mononuclear cells) 31%, 44%, and 80% ( < 0.0001), respectively. Increases in allele burden of RAS-pathway mutations and in numbers of spontaneously formed CFU-GM before and after transformation could be shown in individual patients. Finally, the presence of mutations in RASopathy genes as well as the presence of high colony growth prior to transformation was significantly associated with an increased risk of acute myeloid leukemia (AML) development. Together, RAS-pathway mutations in CMML correlate with an augmented autonomous expansion of neoplastic precursor cells and indicate an increased risk of AML development which may be relevant for targeted treatment strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21083025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215883PMC
April 2020

[Correction to: Therapie der akuten diabetischen Stoffwechselentgleisungen bei Erwachsenen (Update 2019)].

Wien Klin Wochenschr 2019 Aug;131(15-16):389

Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090, Wien, Österreich.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00508-019-01536-5DOI Listing
August 2019

The Austrian biodatabase for chronic myelomonocytic leukemia (ABCMML) : A representative and useful real-life data source for further biomedical research.

Wien Klin Wochenschr 2019 Sep 18;131(17-18):410-418. Epub 2019 Jul 18.

Department of Internal Medicine I with Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz Barmherzige Schwestern - Elisabethinen, Linz, Austria.

In the Austrian biodatabase for chronic myelomonocytic leukemia (ABCMML) clinicolaboratory real-life data have been captured from 606 CMML patients from 14 different hospitals over the last 30 years. It is the only large biodatabase worldwide in which functional methods such as semisolid in vitro cultures complement modern molecular methods such as next generation sequencing. This provides the possibility to comprehensively study the biology of CMML. The aim of this study was to compare patient characteristics with published CMML cohorts and to validate established prognostic parameters in order to examine if this real-life database can serve as a representative and useful data source for further research. After exclusion of patients in transformation characteristics of 531 patients were compared with published CMML cohorts. Median values for age, leukocytes, hemoglobin, platelets, lactate dehydrogenase (LDH) and circulating blasts were within the ranges of reported CMML series. Established prognostic parameters including leukocytes, hemoglobin, blasts and adverse cytogenetics were able to discriminate patients with different outcome. Myeloproliferative (MP) as compared to myelodysplastic (MD)-CMML patients had higher values for circulating blasts, LDH, RAS-pathway mutations and for spontaneous myelomonocytic colony growth in vitro as well as more often splenomegaly. This study demonstrates that the patient cohort of the ABCMML shares clinicolaboratory characteristics with reported CMML cohorts from other countries and confirms phenotypic and genotypic differences between MP-CMML and MD-CMML. Therefore, results obtained from molecular and biological analyses using material from the national cohort will also be applicable to other CMML series and thus may have a more general significance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00508-019-1526-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748886PMC
September 2019

[Treatment of acute diabetic metabolic crises in adults (Update 2019) : Hyperglycemic hyperosmolar state and ketoacidotic metabolic disorders].

Wien Klin Wochenschr 2019 May;131(Suppl 1):196-199

Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090, Wien, Österreich.

Diabetic ketoacidosis (DKA) and the hyperglycemic hyperosmolar state (HHS) represent potentially life-threatening situations in adults. Therefore, rapid comprehensive diagnostic and therapeutic measures with close monitoring of vital and laboratory parameters are required. The treatment of DKA and HHS is essentially the same and replacement of the mostly substantial fluid deficit with several liters of a physiological crystalloid solution is the first and most important step. Serum potassium concentrations need to be carefully monitored to guide its substitution. Regular insulin or rapid acting insulin analogues can be initially administered as an i.v. bolus followed by continuous infusion. Insulin should be switched to subcutaneous injections only after correction of the acidosis and stable glucose concentrations within an acceptable range.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00508-018-1423-zDOI Listing
May 2019

Correction: Different enteral nutrition formulas have no effect on glucose homeostasis but on diet-induced thermogenesis in critically ill medical patients: a randomized controlled trial.

Eur J Clin Nutr 2019 01;73(1):158

Medical University of Vienna, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Intensive Care Unit, Waehringer Guertel 18-20, 1090, Vienna, Austria.

After publication, the author noticed that Table 2 was incorrectly formatted for the final PDF despite being correct in earlier proofs. The table was correct in the HTML version of the article. The EJCN apologizes for the inadvertent error in the formatting of Table 2. The corrected version is uploaded and should be read in conjunction with the original paper. Any inconvenience to the author and readership is regretted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41430-018-0269-9DOI Listing
January 2019

Acid-base status and its clinical implications in critically ill patients with cirrhosis, acute-on-chronic liver failure and without liver disease.

Ann Intensive Care 2018 Apr 19;8(1):48. Epub 2018 Apr 19.

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

Background: Acid-base disturbances are frequently observed in critically ill patients at the intensive care unit. To our knowledge, the acid-base profile of patients with acute-on-chronic liver failure (ACLF) has not been evaluated and compared to critically ill patients without acute or chronic liver disease.

Results: One hundred and seventy-eight critically ill patients with liver cirrhosis were compared to 178 matched controls in this post hoc analysis of prospectively collected data. Patients with and without liver cirrhosis showed hyperchloremic acidosis and coexisting hypoalbuminemic alkalosis. Cirrhotic patients, especially those with ACLF, showed a marked net metabolic acidosis owing to increased lactate and unmeasured anions. This metabolic acidosis was partly antagonized by associated respiratory alkalosis, yet with progression to ACLF resulted in acidemia, which was present in 62% of patients with ACLF grade III compared to 19% in cirrhosis patients without ACLF. Acidemia and metabolic acidosis were associated with 28-day mortality in cirrhosis. Patients with pH values < 7.1 showed a 100% mortality rate. Acidosis attributable to lactate and unmeasured anions was independently associated with mortality in liver cirrhosis.

Conclusions: Cirrhosis and especially ACLF are associated with metabolic acidosis and acidemia owing to lactate and unmeasured anions. Acidosis and acidemia, respectively, are associated with increased 28-day mortality in liver cirrhosis. Lactate and unmeasured anions are main contributors to metabolic imbalance in cirrhosis and ACLF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13613-018-0391-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908779PMC
April 2018

Different enteral nutrition formulas have no effect on glucose homeostasis but on diet-induced thermogenesis in critically ill medical patients: a randomized controlled trial.

Eur J Clin Nutr 2018 04 19;72(4):496-503. Epub 2018 Feb 19.

Medical University of Vienna, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Intensive Care Unit, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Background/objectives: Hyperglycemia is common in critically ill patients and associated with increased mortality. It has been suggested that different nutrition formulas may beneficially influence glucose levels in surgical intensive care patients. In this prospective randomized clinical cohort study we investigated glucose homeostasis in response to different enteral nutrition formulas in medical critically ill patients.

Subjects/methods: 60 medical critically ill patients were randomized to receive continuous fat-based (group A, n = 30) or glucose-based enteral nutrition (group B, n = 30) for seven days. Indirect calorimetry was performed to determine energy demand at baseline and on days 3 and 7. Glucose levels and area under the curve (AUC), insulin demand, glucose variability, and calorie and substrate intake per 24 h were assessed for 7 days.

Results: Over the course of 7 days patients had similar average daily glucose (p = 0.655), glucose AUC (A: 758 (641-829) mg/dl/day vs B: 780 (733-845) mg/dl/day, p = 0.283), similar overall insulin demand (A: 153.5 (45.3-281.5) IE vs B: 167.9 (82.3-283.8) IE, p = 0.525), and received similar amounts of enteral nutrition per 24 h. Resting energy expenditure was similar at baseline (A: 1556 (1227-1808) kcal/day vs B: 1563 (1306-1789) kcal/day, p = 0.882) but energy expenditure increased substantially over time in group A (p < 0.0001), but not in group B (p = 0.097).

Conclusion: Fat-based and glucose-based EN influence glucose homeostasis and insulin demand similarly, yet diet-induced thermogenesis was substantially higher in critically ill patients receiving fat-based enteral nutrition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41430-018-0111-4DOI Listing
April 2018

Acid-base disorders in liver disease.

J Hepatol 2017 11 3;67(5):1062-1073. Epub 2017 Jul 3.

Department of Respiratory and Critical Care Medicine, Otto Wagner Spital, Vienna, Austria. Electronic address:

Alongside the kidneys and lungs, the liver has been recognised as an important regulator of acid-base homeostasis. While respiratory alkalosis is the most common acid-base disorder in chronic liver disease, various complex metabolic acid-base disorders may occur with liver dysfunction. While the standard variables of acid-base equilibrium, such as pH and overall base excess, often fail to unmask the underlying cause of acid-base disorders, the physical-chemical acid-base model provides a more in-depth pathophysiological assessment for clinical judgement of acid-base disorders, in patients with liver diseases. Patients with stable chronic liver disease have several offsetting acidifying and alkalinising metabolic acid-base disorders. Hypoalbuminaemic alkalosis is counteracted by hyperchloraemic and dilutional acidosis, resulting in a normal overall base excess. When patients with liver cirrhosis become critically ill (e.g., because of sepsis or bleeding), this fragile equilibrium often tilts towards metabolic acidosis, which is attributed to lactic acidosis and acidosis due to a rise in unmeasured anions. Interestingly, even though patients with acute liver failure show significantly elevated lactate levels, often, no overt acid-base disorder can be found because of the offsetting hypoalbuminaemic alkalosis. In conclusion, patients with liver diseases may have multiple co-existing metabolic acid-base abnormalities. Thus, knowledge of the pathophysiological and diagnostic concepts of acid-base disturbances in patients with liver disease is critical for therapeutic decision making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2017.06.023DOI Listing
November 2017

Renal tubular acidosis is highly prevalent in critically ill patients.

Crit Care 2015 Apr 6;19:148. Epub 2015 Apr 6.

Department of Medicine III - Division of Gastroenterology and Hepatology, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, 1090, Austria.

Introduction: Hyperchloremic acidosis is frequent in critically ill patients. Renal tubular acidosis (RTA) may contribute to acidemia in the state of hyperchloremic acidosis, but the prevalence of RTA has never been studied in critically ill patients. Therefore, we aimed to investigate the prevalence, type, and possible risk factors of RTA in critically ill patients using a physical-chemical approach.

Methods: This prospective, observational trial was conducted in a medical ICU of a university hospital. One hundred consecutive critically ill patients at the age ≥18, expected to stay in the ICU for ≥24 h, with the clinical necessity for a urinary catheter and the absence of anuria were included. Base excess (BE) subset calculation based on a physical-chemical approach on the first 7 days after ICU admission was used to compare the effects of free water, chloride, albumin, and unmeasured anions on the standard base excess. Calculation of the urine osmolal gap (UOG)--as an approximate measure of the unmeasured urine cation NH4(+)--served as determinate between renal and extrarenal bicarbonate loss in the state of hyperchloremic acidosis.

Results: During the first week of ICU stay 43 of the patients presented with hyperchloremic acidosis on one or more days represented as pronounced negative BEChloride. In 31 patients hyperchloremic acidosis was associated with RTA characterized by a UOG ≤150 mosmol/kg in combination with preserved renal function. However, in 26 of the 31 patients with RTA metabolic acidosis was neutralized by other acid-base disturbances leading to a normal arterial pH.

Conclusions: RTA is highly prevalent in critically ill patients with hyperchloremic acidosis, whereas it is often neutralized by the simultaneous occurrence of other acid-base disturbances.

Trial Registration: Clinicaltrials.gov NCT02392091. Registered 17 March 2015.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13054-015-0890-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404695PMC
April 2015

Resting energy expenditure and substrate oxidation rates correlate to temperature and outcome after cardiac arrest - a prospective observational cohort study.

Crit Care 2015 Mar 29;19:128. Epub 2015 Mar 29.

Department of Medicine III, Division of Gastroenterology and Hepatology, ICU 13H1, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, 1090, Austria.

Introduction: Targeted temperature management improves outcome after cardiopulmonary resuscitation. Reduction of resting energy expenditure might be one mode of action. The aim of this study was to correlate resting energy expenditure and substrate oxidation rates with targeted temperature management at 33°C and outcome in patients after cardiac arrest.

Methods: This prospective, observational cohort study was performed at the department of emergency medicine and a medical intensive care unit of a university hospital. Patients after successful cardiopulmonary resuscitation undergoing targeted temperature management at 33°C for 24 hours with subsequent rewarming to 36°C and standardized sedation, analgesic and paralytic medication were included. Indirect calorimetry was performed five times within 48 h after cardiac arrest. Measurements were correlated to outcome with repeated measures ANOVA, linear and logistic regression analysis.

Results: In 25 patients resting energy expenditure decreased 20 (18 to 27) % at 33°C compared to 36°C without differences between outcome groups (favourable vs. unfavourable: 25 (21 to 26) vs. 21 (16 to 26); P = 0.5). In contrast to protein oxidation rate (favourable vs. unfavourable: 35 (11 to 68) g/day vs. 39 (7 to 75) g/day, P = 0.8) patients with favourable outcome had a significantly higher fat oxidation rate (139 (104 to 171) g/day vs. 117 (70 to 139) g/day, P <0.05) and a significantly lower glucose oxidation rate (30 (-34 to 88) g/day vs. 77 (19 to 138) g/day; P < 0.05) as compared to patients with unfavourable neurological outcome.

Conclusions: Targeted temperature management at 33°C after cardiac arrest reduces resting energy expenditure by 20% compared to 36°C. Glucose and fat oxidation rates differ significantly between patients with favourable and unfavourable neurological outcome.

Trial Registration: Clinicaltrials.gov NCT00500825. Registered 11 July 2007.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13054-015-0856-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404232PMC
March 2015

[The art of treating multiorgan failure].

Med Klin Intensivmed Notfmed 2014 May;109(4):226-7

Interne Abteilung, LKH Kirchdorf, Hausmanningerstraße 8, A-4560 , Kirchdorf, Österreich,

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00063-013-0302-7DOI Listing
May 2014

Evaporation of free water causes concentrational alkalosis in vitro.

Wien Klin Wochenschr 2014 Apr 17;126(7-8):201-7. Epub 2013 Dec 17.

Department of Internal Medicine, Inselspital,University Hospital Bern, Bern, Switzerland.

Background: The development of metabolic alkalosis was described recently in patients with hypernatremia. However, the causes for this remain unknown. The current study serves to clarify whether metabolic alkalosis develops in vitro after removal of free water from plasma and whether this can be predicted by a mathematical model.

Materials And Methods: Ten serum samples of healthy humans were dehydrated by 29 % by vacuum centrifugation corresponding to an increase of the contained concentrations by 41 %. Constant partial pressure of carbon dioxide at 40 mmHg was simulated by mathematical correction of pH [pH(40)]. Metabolic acid-base state was assessed by Gilfix' base excess subsets. Changes of acid-base state were predicted by the physical-chemical model according to Watson.

Results: Evaporation increased serum sodium from 141 (140-142) to 200 (197-203) mmol/L, i.e., severe hypernatremia developed. Acid-base analyses before and after serum concentration showed metabolic alkalosis with alkalemia: pH(40): 7.43 (7.41 to 7.45) vs 7.53 (7.51 to 7.55), p = 0.0051; base excess: 1.9 (0.7 to 3.6) vs 10.0 (8.2 to 11.8), p = 0.0051; base excess of free water: 0.0 (- 0.2 to 0.3) vs 17.7 (16.8 to 18.6), p = 0.0051. The acidifying effects of evaporation, including hyperalbuminemic acidosis, were beneath the alkalinizing ones. Measured and predicted acid-base changes due to serum evaporation agreed well.

Conclusions: Evaporation of water from serum causes concentrational alkalosis in vitro, with good agreement between measured and predicted acid-base values. At least part of the metabolic alkalosis accompanying hypernatremia is independent of renal function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00508-013-0486-0DOI Listing
April 2014

A critique of Stewart's approach: the chemical mechanism of dilutional acidosis.

Intensive Care Med 2009 Dec;35(12):2173-80

Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.

Objective: While Stewart's acid-base approach is increasingly used in clinical practice, it has also led to new controversies. Acid-base disorders can be seen from different viewpoints: on the diagnostic/clinical, quantitative/mathematical, or the mechanistic level. In recent years, confusion in the interpretation and terminology of Stewart's approach has arisen from mixing these different levels. This will be demonstrated on the basis of a detailed analysis of the mechanism of "dilutional acidosis." In the classical dilution concept, metabolic acidosis after resuscitation with large volumes is attributed to the dilution of serum bicarbonate. However, Stewart's approach rejects this explanation and offers an alternative one that is based on a decrease in a "strong ion difference." This mechanistic explanation is questionable for principal chemical reasons. The objective of this study is to clarify the chemical mechanism of dilutional acidosis.

Methods: Experimental data and simulations of various dilution experiments, as well as theoretical and chemical considerations were used.

Results: 1. The key to understanding the mechanism of dilutional acidosis lies in the open CO2/HCO3 (-)-buffer system where the buffer base (HCO3(-)) is diluted whereas the buffer acid is not diluted (constant pCO2). 2. The categorization in independent and dependent variables depends on the system regarded. 3. Neither the principle of electroneutrality, nor a change in [SID], nor increased H2O dissociation plays a mechanistic role.

Conclusion: Stewart's approach is valid at the mathematical level but does not provide any mechanistic insights. However, the quantification and categorization of acid-base disorders, using Stewart approach, may be helpful in clinical practice.

Electronic Supplementary Material: The online version of this article (doi:10.1007/s00134-009-1528-y) contains supplementary material, which is available to authorized users.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00134-009-1528-yDOI Listing
December 2009

The strong ion gap and outcome after cardiac arrest in patients treated with therapeutic hypothermia: a retrospective study.

Intensive Care Med 2009 Feb 14;35(2):232-9. Epub 2008 Oct 14.

Department of Respiratory and Critical Care Medicine, Otto Wagner Spital, Vienna, Austria.

Objective: This study investigates whether the strong ion gap (SIG) is associated with long-term outcome after cardiac arrest in patients treated with therapeutic hypothermia. The hypothesis of the study was that an elevated SIG was associated with unfavourable outcome after cardiac arrest.

Design: Retrospective review of records from 1995 to 2007 of patients who received cardiopulmonary resuscitation.

Setting: Emergency department of a university hospital.

Patients: Patients who were successfully resuscitated after cardiac arrest (n = 288) and treated with mild therapeutic hypothermia.

Interventions: None.

Measurements And Results: Acid-base variables were calculated according to Stewart's approach, as modified by Figge and Fencl, and were determined immediately on admission and 12 h after the return of spontaneous circulation. Acid-base variables were determined at 37 degrees C and are reported without correction for patient temperature. Differences in SIG were compared between patients with favourable (survival 6 months with cerebral performance category 1 or 2) and unfavourable outcomes. SIG on admission and 12 h after return of spontaneous circulation was higher in patients with unfavourable outcome (n = 151; 52%). SIG 12 h after return of spontaneous circulation was identified as an independent predictor of outcome. A SIG > 8.9 mmol/L was associated with an increased cumulative hazard of death.

Conclusions: An elevated SIG 12 h after return of spontaneous circulation may be associated with unfavourable outcome in patients after cardiac arrest treated with mild therapeutic hypothermia. The unmeasured anions hidden behind an elevated SIG may represent markers of tissue damage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00134-008-1315-1DOI Listing
February 2009

Hypernatremia in the critically ill is an independent risk factor for mortality.

Am J Kidney Dis 2007 Dec;50(6):952-7

Intensive Care Unit 13H1, Medical University of Vienna, Sozialmedizinisches Zentrum Baumgartner Höhe-Otto Wagner Spital, Vienna, Austria.

Background: Hypernatremia is common in the intensive care unit (ICU). We assessed the prevalence of hypernatremia and its impact on mortality and ICU length of stay (LOS).

Study Design: Retrospective analysis.

Setting & Participants: All patients admitted to a medical ICU of a university hospital during a 35-month observation period.

Predictor: Hypernatremia (serum sodium > 149 mmol/L) after admission to the ICU.

Outcomes & Measurements: Main outcomes were 28-day hospital mortality and ICU LOS. Demographic factors, main diagnosis, and severity of illness. Cox proportional hazards regression models were used for data analysis.

Results: Of 981 patients, 90 (9%) had hypernatremia, on admission to the ICU in 21 (2%) and developed during the ICU stay in 69 patients (7%). Of these 981 patients, 235 (24%) died; LOS was 8 +/- 9 (SD) days. Mortality rates were 39% and 43% in patients with hypernatremia on admission or that developed after admission compared with 24% in patients without hypernatremia (P < 0.01). LOS was 20 +/- 16 days in patients with hypernatremia compared with 8 +/- 10 days in patients without hypernatremia (P < 0.001). In multivariable analysis, hypernatremia was an independent risk factor for mortality (relative risk, 2.1; 95% confidence interval, 1.4 to 3.3).

Limitations: Retrospective design, absence of data for long-term mortality.

Conclusions: Most cases of hypernatremia in the ICU developed after admission, suggesting an iatrogenic component in its evolution. Hypernatremia is associated with increased mortality. Strategies for preventing hypernatremia in the ICU should be encouraged.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.ajkd.2007.08.016DOI Listing
December 2007

Acid-base disturbances in critically ill patients with cirrhosis.

Liver Int 2007 Sep;27(7):901-9

Department of Respiratory and Critical Care Medicine, Otto Wagner Spital, Vienna, Austria.

Background/aims: The equilibrium of offsetting metabolic acid-base disorders in stable cirrhosis might be lost during episodes of hepatic decompensation, haemorrhage or sepsis. The purpose of this study was to determine whether the acid-base state is destabilized in critically ill patients with cirrhosis and whether this is associated with mortality.

Patients And Method: One-hundred and eighty-one consecutive patients with cirrhosis were investigated in a prospective observational cohort study on admission to a medical intensive care unit (ICU) of a university hospital. Arterial acid-base state was assessed according to the Gilfix methodology. Clinical data, ICU mortality and hospital mortality were recorded.

Main Results: Patients had net metabolic acidosis owing to unmeasured anions and owing to hyperchloraemic, dilutional and lactic acidosis. Lactic acidosis, acidemia and acute renal failure on ICU admission were associated with increased mortality. Lactate and pH discriminated survivors from non-survivors. The presence of lactic acidosis could not always be recognized by customary acid-base parameters.

Conclusion: The stable equilibrium of acid-base disorders is lost when patients with cirrhosis become critically ill. Lactic acidosis and acidaemia are associated with increased ICU mortality caused by severe underlying organ dysfunction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1478-3231.2007.01510.xDOI Listing
September 2007

Severity of insulin resistance in critically ill medical patients.

Metabolism 2007 Jan;56(1):1-5

Intensive Care Unit, Department of Internal Medicine IV, Medical University of Vienna, Vienna, Austria.

Critical illness is characterized by a hypermetabolic state associated with increased mortality, which is partly ascribed to the occurrence of hyperglycemia caused by enhanced endogenous glucose production and insulin resistance (IR). Insulin resistance is well described in patients after surgery and trauma. However, it is less clearly quantified in critically ill medical patients. In this clinical cohort study, IR (M value) was quantified in 40 critically ill medical patients and 25 matched, healthy controls by isoglycemic hyperinsulinemic clamps after an overnight fast on the day after admission to a medical intensive care unit. Energy and substrate metabolism were measured by using indirect calorimetry in the patients before and during the clamp. The severity of illness was assessed by the acute physiology and chronic health evaluation (APACHE) III score. M values of critically ill medical patients were significantly lower compared with healthy controls (2.29 +/- 1.0 and 7.6 +/- 2.9 mg/kg per minute, respectively; P < .001) and were closely related to APACHE III scores (r = -0.43, P < .01), body mass index (r = -0.41, P < .01), and resting energy expenditure (r = 0.40, P < .05). The M value was not associated with age, basal glucose concentrations, and respiratory quotient, and it did not differ among patients with various admission diagnoses. In conclusion, insulin sensitivity was found to be reduced by 70% in critically ill medical patients. The severity of IR was associated with the severity of illness, body mass index, and resting energy expenditure, but not with substrate oxidation rates. In addition, the severity of IR did not vary among patients with different admission diagnoses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.metabol.2006.08.014DOI Listing
January 2007

The acidifying effect of lactate is neutralized by the alkalinizing effect of hypoalbuminemia in non-paracetamol-induced acute liver failure.

J Hepatol 2006 Sep 25;45(3):387-92. Epub 2006 Apr 25.

Klinik fuer Innere Medizin IV, ICU 13H1, Medical University of Vienna, Allgemeines Krankenhaus, Waehringerguertel 18-20, A - 1090 Vienna, Austria.

Background/aims: Hyperlactatemia with unexplained absence of metabolic acidosis is observed in acute liver failure. In chronic liver disease offsetting metabolic acid-base disorders could be revealed by means of physical-chemical acid-base analysis. The purpose of this study was to determine whether the acidifying effect of lactate is neutralized by the alkalinizing effect of hypoalbuminemia in acute liver failure.

Methods: Serial arterial blood samples of 46 consecutive patients with non-paracetamol-induced acute liver failure were studied after admission to a medical ICU in a prospective investigation and compared to healthy controls. Acid-base state was assessed by quantitative physical-chemical analysis.

Results: Lactate was increased and albumin was decreased in patients with acute liver failure compared to healthy controls resulting in normal net metabolic acid-base state. The alkalinizing effect of hypoalbuminemia was neutralized by the acidifying effect of elevated lactate. This observation was confirmed in serial analysis during 5 days after admission.

Conclusions: The acidifying effect of lactate is neutralized by the alkalinizing effect of hypoalbuminemia in non-paracetamol-induced acute liver failure. The absence of apparent metabolic acidosis in the presence of elevated lactate can be explained by means of the physical-chemical acid-base model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2006.03.011DOI Listing
September 2006

Images in cardiovascular medicine. Bubble in the heart: a rare cause of mitral regurgitation.

Circulation 2006 Mar;113(10):e401-2

Public Hospital Elisabethinen Linz, University of Innsbruck and Vienna, Innsbruck and Vienna, Austria.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.105.565036DOI Listing
March 2006

Weight-adjusted resting energy expenditure is not constant in critically ill patients.

Intensive Care Med 2006 Mar 14;32(3):428-34. Epub 2006 Feb 14.

Medical University of Vienna, Intensive Care Unit, Department of Internal Medicine IV, Waehringer-Guertel 18-20, 1090, Vienna, Austria.

Objective: In critically ill patients, energy requirements are frequently calculated as a multiple of total body weight presuming a linear relationship between total body weight and resting energy expenditure (REE); however, it is doubtful if this estimation of energy needs should be applied to all patients, particularly to overweight patients, since adipose tissue has a low contribution to REE. This study was undertaken to test the hypothesis that REE adjusted for total body weight decreases with increasing body mass index in critically ill patients. Additionally, measured REE was compared with three predictive equations.

Design And Setting: Clinical study in a university hospital intensive care unit.

Patients: One hundred critically ill patients admitted to the intensive care unit.

Measurements And Results: Patients were included into four groups according to their body mass index (normal weight, pre-obese, obese, and morbidly obese). Measured REE was assessed using indirect calorimetry. Energy needs were calculated using the basal metabolic rate, the Consensus Statement of the American College of Chest Physicians (REEacs), and 25[Symbol: see text]kcal/kg of ideal body weight (REEibw). Adjusted REE was 24.8 +/- 5.5 kcal/kg in normal weight, 22.0 +/- 3.7 kcal/kg in pre-obese, 20.4 +/- 2.6 kcal/kg in obese, and 16.3 +/- 2.3 kcal/kg in morbidly obese patients (p < 0.01). Basal metabolic rate underestimated measured REE in normal weight and pre-obese patients. REEacs and REEibw over- and underestimated measured REE in overweight patients, respectively.

Conclusions: Predictive equations were not able to estimate measured REE adequately in all the patients. Adjusted REE decreased with increasing body mass index; thus, a body mass index group-specific adaptation for the estimation of energy needs should be applied.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00134-005-0056-7DOI Listing
March 2006

Equilibrium of acidifying and alkalinizing metabolic acid-base disorders in cirrhosis.

Liver Int 2005 Jun;25(3):505-12

Fourth Medical Department, Medical University of Vienna, Austria.

Background And Aims: Conflicting results exist with regard to metabolic acid-base status in liver cirrhosis, when the classic concept of acid-base analysis is applied. The influence of the common disturbances of water, electrolytes and albumin on acid-base status in cirrhosis has not been studied. The aim of this study was to clarify acid-base status in cirrhotic patients by analyzing all parameters with possible impact on acid-base equilibrium.

Patients And Methods: Fifty stable cirrhotic patients admitted to a university hospital. Arterial acid-base status was analyzed using the principles of physical chemistry and compared with 10 healthy controls.

Results: Apart from mild hypoalbuminemic alkalosis, acid-base state was normal in Child-Pugh A cirrhosis. Respiratory alkalosis was the net acid-base disorder in Child-Pugh B and C cirrhosis with a normal overall metabolic acid-base state (Base excess-1.0 (-3.6 to 1.6) vs 1.1 (-0.2 to 1.1) mmol/l, P = 0.136, compared with healthy controls, median (interquartile range)). Absence of an apparent metabolic acid-base disorder was based on an equilibrium of hypoalbuminemic alkalosis and of dilutional acidosis and hyperchloremic acidosis.

Conclusion: A balance of offsetting acidifying and alkalinizing metabolic acid-base disorders leaves the net metabolic acid-base status unchanged in cirrhosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1478-3231.2005.01013.xDOI Listing
June 2005

Immunohistochemical detection of VEGF in the bone marrow of patients with chronic myeloid leukemia and correlation with the phase of disease.

Am J Clin Pathol 2004 Apr;121(4):473-81

Department of Internal Medicine I, Medical University of Vienna, Austria.

We studied expression of vascular endothelial growth factor (VEGF) in paraffin-embedded bone marrow sections obtained from 15 patients with chronic myeloid leukemia (CML) in chronic phase (CP), 3 in accelerated phase (AP), 7 in myeloid blast phase (BP(M)), 6 in lymphoid blast phase (BP(L)), and in 3 normal bone marrow samples. VEGF expression was determined immunohistochemically by using an anti-VEGF antibody. In CML-CP, the distribution of VEGF showed a pattern similar to that of normal marrow. VEGF was expressed in myeloid progenitors and megakaryocytes and less abundantly in mature granulomonocytic cells, whereas erythroid cells did not stain positively for VEGF. In CML-BP(M), myeloblasts expressed substantial amounts of VEGF. By contrast, little if any VEGF was detectable in blast cells in CML-BP(L). VEGF messenger RNA (mRNA) was detected in leukemic cells in CML-BP(M) by reverse transcriptase-polymerase chain reaction, whereas blast cells in CML-BP(L) did not express substantial amounts of VEGF mRNA. Our data show that VEGF is expressed in immature myeloid cells in CML. The extent of VEGF expression depends on the phase of disease and the cell type involved in disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1309/3JLT-FNNE-DQHB-4A0PDOI Listing
April 2004

Randomized multicenter phase II trial of two different schedules of capecitabine plus oxaliplatin as first-line treatment in advanced colorectal cancer.

J Clin Oncol 2003 Apr;21(7):1307-12

Department of Internal Medicine I, Division of Clinical Oncology, University Hospital of Vienna, Austria.

Purpose: Capecitabine and oxaliplatin, two new agents with potential synergistic activity, have demonstrated promising antitumor efficacy in advanced colorectal cancer (ACC). Preclinical and clinical evidence indicating that dose intensification of the oral fluorouracil prodrug might result in improved therapeutic results led us to the present randomized multicenter phase II study.

Patients And Methods: Eighty-nine patients with bidimensionally measurable ACC previously untreated for metastatic disease were randomly allocated to receive oxaliplatin 130 mg/m(2) day 1 plus capecitabine 2,000 mg/m(2)/d days 1 to 14 every 3 weeks (arm A) or to receive oxaliplatin 85 mg/m(2) days 1 and 14 combined with capecitabine 3,500 mg/m(2) days 1 to 7 and 14 to 21 every 4 weeks (arm B). In both treatment arms, chemotherapy was continued for a total of 6 months unless there was prior evidence of progression of disease.

Results: Patients allocated to the high-dose capecitabine combination arm B had a higher radiologically confirmed response rate (54.5% v 42.2%) and a significantly longer median progression-free survival time than those allocated to control arm A (10.5 v 6.0 months; P =.0013). Median overall survival times cannot be calculated for either treatment arm at this point. Despite a 34% higher dose intensity of capecitabine in arm B, there was no difference in hematologic toxicity between treatment arms (neutropenia/thrombocytopenia: 60%/43% in arm B v 56%/33% in arm A). Similarly, the incidence rate and degree of nonhematologic adverse events were comparable: The most commonly encountered symptoms (all grades, arm A and arm B) included nausea/emesis (A: 58%; B: 62%), diarrhea (A: 44%; B: 31%), peripheral sensory neuropathy (A: 80%; B: 83%), and fatigue (A: 40%; B: 50%).

Conclusion: Results of this study indicate that both combination regimens are feasible, tolerable, and clinically active. The dose-intensified bimonthly capecitabine arm, however, seems to be more effective in increasing both response rate and progression-free survival time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2003.09.016DOI Listing
April 2003

Randomized multicenter phase II trial of oxaliplatin plus irinotecan versus raltitrexed as first-line treatment in advanced colorectal cancer.

J Clin Oncol 2002 Jan;20(1):165-72

Department of Internal Medicine I, Division of Oncology, Vienna University Medical School. Waeringer Guertel 18-20, A-1090 Vienna, Austria.

Purpose: Irinotecan and oxaliplatin are two new agents with promising activity in advanced colorectal cancer. Based on preclinical and clinical evidence that both drugs act synergistically, a randomized phase II study was initiated to investigate the therapeutic potential and tolerance of this combination in the front-line setting.

Patients And Methods: Ninety-two patients with previously untreated, measurable disease were randomized to receive biweekly oxaliplatin 85 mg/m(2) plus irinotecan 175 mg/m(2) or raltitrexed 3 mg/m(2) given on day 1 every 3 weeks. Upon development of progressive disease, second-line treatment with the opposite arm was effected.

Results: Patients allocated to oxaliplatin/irinotecan had a significantly better radiologically confirmed response rate (43.5% v 19.6%; P =.0025) and longer progression-free survival (median, 7.1 v 5.0 months; P =.0033). Improvement in overall survival, however, did not reach the level of significance (median, 16.0 v 16.5 months; P =.3943). The response rate after cross-over was 33.3% (eight of 24) for assessable patients treated with oxaliplatin/irinotecan compared with 14.2% (three of 21) for those treated with second-line raltitrexed. Oxaliplatin/irinotecan caused more hematologic and gastrointestinal toxicities, necessitating dose reductions in 10 of the first 20 patients. After adjustment of the irinotecan starting dose from 175 to 150 mg/m(2), tolerance of treatment was acceptable; the most commonly encountered events (all grades) were neutropenia (81%), alopecia (65%), nausea/emesis (62%), peripheral sensory neuropathy (62%), and diarrhea (46%).

Conclusion: Oxaliplatin/irinotecan seems beneficial as first-line therapy in advanced colorectal cancer, with an acceptable toxicity profile at the reduced irinotecan dose level. Its promising therapeutic potential is supported by the high response activity noted in the raltitrexed control arm after cross-over, which may also explain the lack of a difference in overall survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2002.20.1.165DOI Listing
January 2002
-->