Publications by authors named "Christian Rabe"

51 Publications

Clinical effect of ethanol co-use in patients with acute drug toxicity involving the use of central nervous system depressant recreational drugs.

Eur J Emerg Med 2022 Aug 8;29(4):291-300. Epub 2022 Apr 8.

Division of Clinical Toxicology and Poison Control Centre Munich, Department of Internal Medicine II, TUM School of Medicine, Technical University of Munich, Germany.

Background And Importance: Patients who use recreational drugs frequently co-ingest ethanol, which is considered a central nervous system (CNS) depressant. The clinical relevance of this in acute toxicity involving other CNS depressants is not well described.

Objective: To assess the clinical impact of ethanol co-use in patients presenting to the emergency department (ED) with acute toxicity involving the use of CNS depressant drugs.

Design, Settings And Participants: A retrospective multicentre study using data from the Euro-DEN Plus database from January 2014 to December 2019.

Outcomes Measure And Analysis: Comparison of epidemiologic and clinical characteristics, ED and hospital management of patients with CNS depressant intoxication with or without ethanol co-use.

Main Results: Although 7644 (17.5%) of the 43 633 presentations were included, ethanol was co-ingested in 3811 (49.9%). In total 53.3% required medical treatment, 14 patients died. Patients with ethanol co-use more frequently presented with a Glasgow Coma Scale (GCS) ≤8 (34.1% vs. 22.4%; P   <  0.001), vomiting (8.1% vs. 4.6%; P   <  0.001), anxiety (12 % vs. 6.4%; P   <  0.001), agitation/aggression (22% vs. 14.7%; P   <  0.001), seizures (3.8% vs. 2.4%; P   <  0.001) and hypotension (7.5% vs. 4.6%; P   <  0.001). They more often required ambulance transport (85.5% vs. 76.5%; P   <  0.001), medical treatment (57.3% vs. 48.0%; P   <  0.001), hospitalization (27.7% vs. 18.9%; P   <  0.001), and admission to intensive care (12.2% vs. 4.0%; P   <  0.001). Subgroup analysis showed that GCS ≤8 was particularly common in patients who combined ethanol with opioids or gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL).

Conclusion: Co-use of ethanol with CNS-depressant drugs appears to increase the risk of adverse effects and is associated with a higher need for medical treatment, especially when ethanol is combined with opioids or GHB/GBL.
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http://dx.doi.org/10.1097/MEJ.0000000000000932DOI Listing
August 2022

Clinical effect of ethanol co-use in patients with acute drug toxicity involving the use of central nervous system depressant recreational drugs.

Eur J Emerg Med 2022 Aug 8;29(4):291-300. Epub 2022 Apr 8.

Division of Clinical Toxicology and Poison Control Centre Munich, Department of Internal Medicine II, TUM School of Medicine, Technical University of Munich, Germany.

Background And Importance: Patients who use recreational drugs frequently co-ingest ethanol, which is considered a central nervous system (CNS) depressant. The clinical relevance of this in acute toxicity involving other CNS depressants is not well described.

Objective: To assess the clinical impact of ethanol co-use in patients presenting to the emergency department (ED) with acute toxicity involving the use of CNS depressant drugs.

Design, Settings And Participants: A retrospective multicentre study using data from the Euro-DEN Plus database from January 2014 to December 2019.

Outcomes Measure And Analysis: Comparison of epidemiologic and clinical characteristics, ED and hospital management of patients with CNS depressant intoxication with or without ethanol co-use.

Main Results: Although 7644 (17.5%) of the 43 633 presentations were included, ethanol was co-ingested in 3811 (49.9%). In total 53.3% required medical treatment, 14 patients died. Patients with ethanol co-use more frequently presented with a Glasgow Coma Scale (GCS) ≤8 (34.1% vs. 22.4%; P   <  0.001), vomiting (8.1% vs. 4.6%; P   <  0.001), anxiety (12 % vs. 6.4%; P   <  0.001), agitation/aggression (22% vs. 14.7%; P   <  0.001), seizures (3.8% vs. 2.4%; P   <  0.001) and hypotension (7.5% vs. 4.6%; P   <  0.001). They more often required ambulance transport (85.5% vs. 76.5%; P   <  0.001), medical treatment (57.3% vs. 48.0%; P   <  0.001), hospitalization (27.7% vs. 18.9%; P   <  0.001), and admission to intensive care (12.2% vs. 4.0%; P   <  0.001). Subgroup analysis showed that GCS ≤8 was particularly common in patients who combined ethanol with opioids or gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL).

Conclusion: Co-use of ethanol with CNS-depressant drugs appears to increase the risk of adverse effects and is associated with a higher need for medical treatment, especially when ethanol is combined with opioids or GHB/GBL.
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http://dx.doi.org/10.1097/MEJ.0000000000000932DOI Listing
August 2022

Effect of plasma exchange on colchicine elimination in overdose - a case report.

Clin Toxicol (Phila) 2021 09 8;59(9):849-850. Epub 2021 Feb 8.

Division of Clinical Toxicology, Department of Internal Medicine II, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

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http://dx.doi.org/10.1080/15563650.2021.1877298DOI Listing
September 2021

Bilateral Basal Ganglion Hemorrhage after Severe Olanzapine Intoxication.

Case Rep Psychiatry 2020 31;2020:2398721. Epub 2020 Aug 31.

Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Department of Neurology, München, Germany.

Olanzapine is a second-generation antipsychotic drug which is generally considered safe with well therapeutic antipsychotic effects. We describe a patient suffering from bilateral intracerebral hemorrhage after severe olanzapine intoxication without underlying thrombocytopenia, arterial hypertension, or vascular malformation as cause of intracerebral hemorrhage. This raises the possibility of a direct side effect of high-dose olanzapine intake. So far, intracranial hemorrhage after olanzapine intoxication in such constellation has not been reported before. Given the high number of its prescription rates, our finding of intracranial hemorrhage after olanzapine intoxication is of high clinical relevance.
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http://dx.doi.org/10.1155/2020/2398721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481995PMC
August 2020

Therapy limitation in octogenarians in German intensive care units is associated with a longer length of stay and increased 30 days mortality: A prospective multicenter study.

J Crit Care 2020 12 1;60:58-63. Epub 2020 Aug 1.

Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Hospital Düsseldorf, Germany; Cardiovascular Research Institute Düsseldorf (CARID), Düsseldorf, Germany.

Purpose: The approach to limit therapy in very old intensive care unit patients (VIPs) significantly differs between regions. The focus of this multicenter analysis is to illuminate, whether the Clinical Frailty Scale (CFS) is a suitable tool for risk stratification in VIPs admitted to intensive care units (ICUs) in Germany. Furthermore, this investigation elucidates the impact of therapeutic limitation on the length of stay and mortality in this setting.

Methods: German cohorts' data from two multinational studies (VIP-1, VIP-2) were combined. Univariate and multivariate logistic regression were used to evaluate associations with mortality.

Results: 415 acute VIPs were included. Frail VIPs (CFS > 4) were older (85 [IQR 82-88] vs. 83 [IQR 81-86] years p < .001) and suffered from an increased 30-day-mortality (43.4% versus 23.9%, p < .0001). CFS was an independent predictor of 30-day-mortality in a multivariate logistic regression model (aOR 1.23 95%CI 1.04-1.46 p = .02). Patients with any limitation of life-sustaining therapy had a significantly increased 30-day mortality (86% versus 16%, p < .001) and length of stay (144 [IQR 72-293] versus 96 [IQR 47.25-231.5] hours, p = .026).

Conclusion: In German ICUs, any limitation of life-sustaining therapy in VIPs is associated with a significantly increased ICU length of stay and mortality. CFS reliably predicts the outcome.
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http://dx.doi.org/10.1016/j.jcrc.2020.07.024DOI Listing
December 2020

Surviving chlormequat poisoning - pharmacokinetics and the role of atropine.

Clin Toxicol (Phila) 2021 01 27;59(1):74-76. Epub 2020 Apr 27.

Division of Clinical Toxicology and Poison Control Centre Munich, Department of Internal Medicine II, School of Medicine, Technical University of Munich, Munich, Germany.

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http://dx.doi.org/10.1080/15563650.2020.1758326DOI Listing
January 2021

Sustained low efficiency dialysis should not be interrupted for performing transpulmonary thermodilution measurements.

Ann Intensive Care 2018 Nov 23;8(1):113. Epub 2018 Nov 23.

Division of Clinical Toxicology and Poison Control Centre Munich, Department of Internal Medicine II, TUM School of Medicine, Technical University of Munich, Munich, Germany.

Background: Treatment of multiple organ failure frequently requires enhanced hemodynamic monitoring. When renal replacement is indicated, it remains unclear whether transpulmonary thermodilution (TPTD) measurements are influenced by renal replacement therapy (RRT) and whether RRT should be paused for TPTD measurements. Our aim was therefore to investigate the effect of pausing RRT on TPTD results in two dialysis catheter locations.

Materials And Methods: In total, 62 TPTD measurements in 24 patients (APACHE: 32 ± 7 [mean ± standard deviation (SD)]) were performed using the PiCCO™ system (Pulsion, Germany). Patients were treated with sustained low efficiency dialysis (SLED; Genius™ system, Fresenius, Germany) as RRT. Measurements were taken during ongoing hemodialysis (HD, HDO), during paused HD (HDP) and immediately after termination of HD and blood restitution (HDT). Dialysis catheters were placed either in the superior vena cava (SVC, 19 times) or in the inferior vena cava (IVC, 5 times). Statistical analysis was performed to assess the effects of the measurement setting, SLED (blood flow rate) and the catheter location, on cardiac index (CI), global end-diastolic volume index (GEDVI) and extravascular lung water index (EVLWI) as measured by TPTD. Multilevel models were used for the analysis due to the triplicate measurements and due to 12 out of 19 SVC and 2 out of 5 IVC patients having more than one TPTD measured.

Results: CI and GEDVI were significantly higher at time point HDP compared to both HDO and HDT. In contrast, values for EVLWI were lower at HDP when compared to HDO and HDT. These findings were independent of the site of dialysis catheter insertion and blood flow rate.

Conclusions: PiCCO™ measurements assessed at paused SLED significantly deviate from ongoing and terminated SLED. Therefore, the dialysis system should not be paused for measurements. TPTD measurements in patients with PiCCO monitoring seem sufficiently reliable during ongoing SLED as well as after its termination. An effect of dialysis catheter location (SVC vs IVC) and blood flow rate on PiCCO™ measurements could not be shown.
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http://dx.doi.org/10.1186/s13613-018-0455-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251800PMC
November 2018

Clinical Frailty Scale (CFS) reliably stratifies octogenarians in German ICUs: a multicentre prospective cohort study.

BMC Geriatr 2018 07 13;18(1):162. Epub 2018 Jul 13.

Division of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany.

Background: In intensive care units (ICU) octogenarians become a routine patients group with aggravated therapeutic and diagnostic decision-making. Due to increased mortality and a reduced quality of life in this high-risk population, medical decision-making a fortiori requires an optimum of risk stratification. Recently, the VIP-1 trial prospectively observed that the clinical frailty scale (CFS) performed well in ICU patients in overall-survival and short-term outcome prediction. However, it is known that healthcare systems differ in the 21 countries contributing to the VIP-1 trial. Hence, our main focus was to investigate whether the CFS is usable for risk stratification in octogenarians admitted to diversified and high tech German ICUs.

Methods: This multicentre prospective cohort study analyses very old patients admitted to 20 German ICUs as a sub-analysis of the VIP-1 trial. Three hundred and eight patients of 80 years of age or older admitted consecutively to participating ICUs. CFS, cause of admission, APACHE II, SAPS II and SOFA scores, use of ICU resources and ICU- and 30-day mortality were recorded. Multivariate logistic regression analysis was used to identify factors associated with 30-day mortality.

Results: Patients had a median age of 84 [IQR 82-87] years and a mean CFS of 4.75 (± 1.6 standard-deviation) points. More than half of the patients (53.6%) were classified as frail (CFS ≥ 5). ICU-mortality was 17.3% and 30-day mortality was 31.2%. The cause of admission (planned vs. unplanned), (OR 5.74) and the CFS (OR 1.44 per point increase) were independent predictors of 30-day survival.

Conclusions: The CFS is an easy determinable valuable tool for prediction of 30-day ICU survival in octogenarians, thus, it may facilitate decision-making for intensive care givers in Germany.

Trial Registration: The VIP-1 study was retrospectively registered on ClinicalTrials.gov (ID: NCT03134807 ) on May 1, 2017.
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http://dx.doi.org/10.1186/s12877-018-0847-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044022PMC
July 2018

Clinical Frailty Scale (CFS) reliably stratifies octogenarians in German ICUs: a multicentre prospective cohort study.

BMC Geriatr 2018 07 13;18(1):162. Epub 2018 Jul 13.

Division of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany.

Background: In intensive care units (ICU) octogenarians become a routine patients group with aggravated therapeutic and diagnostic decision-making. Due to increased mortality and a reduced quality of life in this high-risk population, medical decision-making a fortiori requires an optimum of risk stratification. Recently, the VIP-1 trial prospectively observed that the clinical frailty scale (CFS) performed well in ICU patients in overall-survival and short-term outcome prediction. However, it is known that healthcare systems differ in the 21 countries contributing to the VIP-1 trial. Hence, our main focus was to investigate whether the CFS is usable for risk stratification in octogenarians admitted to diversified and high tech German ICUs.

Methods: This multicentre prospective cohort study analyses very old patients admitted to 20 German ICUs as a sub-analysis of the VIP-1 trial. Three hundred and eight patients of 80 years of age or older admitted consecutively to participating ICUs. CFS, cause of admission, APACHE II, SAPS II and SOFA scores, use of ICU resources and ICU- and 30-day mortality were recorded. Multivariate logistic regression analysis was used to identify factors associated with 30-day mortality.

Results: Patients had a median age of 84 [IQR 82-87] years and a mean CFS of 4.75 (± 1.6 standard-deviation) points. More than half of the patients (53.6%) were classified as frail (CFS ≥ 5). ICU-mortality was 17.3% and 30-day mortality was 31.2%. The cause of admission (planned vs. unplanned), (OR 5.74) and the CFS (OR 1.44 per point increase) were independent predictors of 30-day survival.

Conclusions: The CFS is an easy determinable valuable tool for prediction of 30-day ICU survival in octogenarians, thus, it may facilitate decision-making for intensive care givers in Germany.

Trial Registration: The VIP-1 study was retrospectively registered on ClinicalTrials.gov (ID: NCT03134807 ) on May 1, 2017.
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http://dx.doi.org/10.1186/s12877-018-0847-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044022PMC
July 2018

Independent validation of the ICU requirement score in a cohort of acutely poisoned adults.

Clin Toxicol (Phila) 2018 07 16;56(7):664-666. Epub 2017 Nov 16.

a Department of Clinical Toxicology , Klinikum Rechts der Isar, Technical University of Munich , Munich , Germany.

Objective: To independently validate the predictive value of the intensive care requirement score (IRS) in unselected poisoned patients.

Design: Retrospective chart review.

Patients And Methods: Five hundred and seventeen out of 585 admissions for acute intoxications could be analyzed. Eleven were excluded for a condition already requiring intensive care unit (ICU) support at admission (e.g., preclinical intubation). A further 57 admissions were excluded due to missing data. The IRS was calculated using a point-scoring system including age, Glasgow Coma Scale, heart rate, type of intoxication, and preexisting conditions. It was then compared to a composite endpoint indicating an ICU requirement (death in hospital, vasopressors, need for ventilation). The endpoint and the point-scoring system were identical to the original publication of the score.

Results And Conclusion: Twenty-three out of 517 patients had a complicated clinical course as defined by meeting the endpoint definition. Twenty-one out of 23 complicated courses had a positive IRS (defined as greater or equal 6 points), as compared to 255/494 patients with an uncomplicated clinical course (p < .001, Fisher's exact test). One patient (with a positive IRS) died. The negative predictive value of the IRS was 0.99 (95% CI: 0.97-1), the sensitivity was 0.91 and the specificity 0.48. In conclusion, the IRS is significantly linked to outcome. While a negative IRS virtually excludes the need for ICU care, a positive IRS has a positive predictive value too low to be used for risk stratification. The IRS could also be applied to unselected admissions of poisoned patients.
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http://dx.doi.org/10.1080/15563650.2017.1401635DOI Listing
July 2018

An internet-based survey of 96 German-speaking users of "bath salts": frequent complications, risky sexual behavior, violence, and delinquency.

Clin Toxicol (Phila) 2018 03 28;56(3):219-222. Epub 2017 Jul 28.

a Department of Clinical Toxicology, Klinikum rechts der Isar , Technical University of Munich , Munich , Germany.

Objective: To define the demographics of German-speaking "bath salt" users.

Design: Prospective web-based survey of volunteer users of "bath salts". Subject recruitment/exclusion: Participation was solicited by posts in web forums frequented by users of synthetic cathinones. An invitation to participate was also disseminated via regional drug information centers. Responses were discarded if participants refused data analysis, provided incomplete surveys, were under 18 years of age (five cases), and in case of clearly improbable answers (i.e., two cases with profanity typed in free-form input fields). Overall 96 out of 180 participants provided complete questionnaires. These were further analyzed.

Results And Conclusions: 74% of respondents were male. 41% were under the age of 30 and a further 38% between 30 and 39 years old. Cathinones were used on more than 10 days in the preceding year by 62% of study subjects. The nasal and intravenous routes of administration were most often used. About 80% of respondents reported binge use. There were frequent co-administrations of opioids and opiates. The most common complication was prolonged confusion (47%). 16% had been involuntarily confined. One third had thoughts of violence and 16% acted on these thoughts either against themselves or others. About 44% reported high-risk sexual activity under the influence of cathinones. About 31% had driven or ridden a bike while intoxicated. About 6% had problems with law-enforcement for selling cathinones and 16% for crimes committed under the influence of cathinones. In conclusion, cathinone users are typically young males in their twenties and thirties. Most are experienced drug users, particularly of alcohol and opiates/opioids. The impact on society is tremendous as evidenced by high rates of self-reported violence, high-risk sexual activity, crimes, and traffic violations.
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http://dx.doi.org/10.1080/15563650.2017.1353094DOI Listing
March 2018

[Poison in the garden: Poisonous plants relevant to clinical toxicology].

MMW Fortschr Med 2017 Jun;159(12):46-49

Abteilung für klinische Toxikologie, Klinikum rechts der Isar, Technische Universität München, München, Deutschland.

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http://dx.doi.org/10.1007/s15006-017-9847-3DOI Listing
June 2017

Intoxication by gamma hydroxybutyrate and related analogues: Clinical characteristics and comparison between pure intoxication and that combined with other substances of abuse.

Toxicol Lett 2017 Aug 1;277:84-91. Epub 2017 Jun 1.

Department of Clinical Toxicology, Klinikum rechts der Isar, Technical University of Munich, Germany.

Objective: To study the profile of European gamma-hydroxybutyrate (GHB) and gammabutyrolactone (GBL) intoxication and analyse the differences in the clinical manifestations produced by intoxication by GHB/GBL alone and in combination with other substances of abuse.

Method: We prospectively collected data on all the patients attended in the Emergency Departments (ED) of the centres participating in the Euro-DEN network over 12 months (October 2013 to September 2014) with a primary presenting complaint of drug intoxication (excluding ethanol alone) and registered the epidemiological and clinical data and outcomes.

Results: We included 710 cases (83% males, mean age 31 years), representing 12.6% of the total cases attended for drug intoxication. Of these, 73.5% arrived at the ED by ambulance, predominantly during weekend, and 71.7% consumed GHB/GBL in combination with other substances of abuse, the most frequent additional agents being ethanol (50%), amphetamine derivatives (36%), cocaine (12%) and cannabis (8%). Among 15 clinical features pre-defined in the project database, the 3 most frequently identified were altered behaviour (39%), reduced consciousness (34%) and anxiety (14%). The severity ranged from mild cases requiring no treatment (308 cases, 43.4%) to severe cases requiring admission to intensive care (103 cases, 14.6%) and mechanical ventilation (49 cases, 6.9%). No deaths were reported. In comparison with only GHB/GBL consumption, patients consuming GHB/GBL with co-intoxicants presented more vomiting (15% vs. 3%, p<0.001) and cardiovascular symptoms (5.3% vs. 1.5%, p<0.05), a greater need for treatment (59.8% vs. 48.3%, p<0.01) and a longer ED stay (11.3% vs. 3.6% patients with ED stay >12h, p<0.01).

Conclusions: The profile of the typical GHB/GBL-intoxicated European is a young male, requiring care for altered behaviour and reduced level of consciousness, mainly during the weekend. The clinical features are more severe when GHB is consumed in combination with other substances of abuse.
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http://dx.doi.org/10.1016/j.toxlet.2017.05.030DOI Listing
August 2017

Outcome of acute respiratory distress syndrome in university and non-university hospitals in Germany.

Crit Care 2017 May 30;21(1):122. Epub 2017 May 30.

Department of Anaesthesiology and Intensive Care Medicine, Charité University Hospital, Berlin, Germany.

Background: This study investigates differences in treatment and outcome of ventilated patients with acute respiratory distress syndrome (ARDS) between university and non-university hospitals in Germany.

Methods: This subanalysis of a prospective, observational cohort study was performed to identify independent risk factors for mortality by examining: baseline factors, ventilator settings (e.g., driving pressure), complications, and care settings-for example, case volume of ventilated patients, size/type of intensive care unit (ICU), and type of hospital (university/non-university hospital). To control for potentially confounding factors at ARDS onset and to verify differences in mortality, ARDS patients in university vs non-university hospitals were compared using additional multivariable analysis.

Results: Of the 7540 patients admitted to 95 ICUs from 18 university and 62 non-university hospitals in May 2004, 1028 received mechanical ventilation and 198 developed ARDS. Although the characteristics of ARDS patients were very similar, hospital mortality was considerably lower in university compared with non-university hospitals (39.3% vs 57.5%; p = 0.012). Treatment in non-university hospitals was independently associated with increased mortality (OR (95% CI): 2.89 (1.31-6.38); p = 0.008). This was confirmed by additional independent comparisons between the two patient groups when controlling for confounding factors at ARDS onset. Higher driving pressures (OR 1.10; 1 cmHO increments) were also independently associated with higher mortality. Compared with non-university hospitals, higher positive end-expiratory pressure (PEEP) (mean ± SD: 11.7 ± 4.7 vs 9.7 ± 3.7 cmHO; p = 0.005) and lower driving pressures (15.1 ± 4.4 vs 17.0 ± 5.0 cmHO; p = 0.02) were applied during therapeutic ventilation in university hospitals, and ventilation lasted twice as long (median (IQR): 16 (9-29) vs 8 (3-16) days; p < 0.001).

Conclusions: Mortality risk of ARDS patients was considerably higher in non-university compared with university hospitals. Differences in ventilatory care between hospitals might explain this finding and may at least partially imply regionalization of care and the export of ventilatory strategies to non-university hospitals.
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http://dx.doi.org/10.1186/s13054-017-1687-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5448143PMC
May 2017

Synthetic cathinones in Southern Germany - characteristics of users, substance-patterns, co-ingestions, and complications.

Clin Toxicol (Phila) 2017 Jul 28;55(6):573-578. Epub 2017 Mar 28.

a Department of Clinical Toxicology , Klinikum rechts der Isar, Technical University of Munich , Munich , Germany.

Objective: To define the characteristics of synthetic cathinone users admitted to hospital including clinical and laboratory parameters and the complications of use.

Design: Retrospective single-center study of patients treated for acute cathinone intoxication and complications of cathinone use between January 2010 and January 2016.

Setting: A specialized clinical toxicology unit at an academic tertiary care center in Southern Germany serving a population of about 4 million.

Patients And Methods: 81 consecutive patients with laboratory-confirmed use of cathinones who presented for acute intoxication or complications of cathinone use were retrospectively analyzed.

Results And Conclusions: The patients were predominantly male (64%, 52/81) with a median age of 34 years. 60 were admitted for signs of acute intoxication while 21 suffered from complications of cathinone use. 70% of acutely intoxicated patients had an increased creatinine phosphokinase. Only a minority of patients presented with a sympathomimetic toxidrome. Three patients had infectious complications, 10 prolonged psychosis, 6 rhabdomyolyses and/or kidney failure, and two patients died. Based on presentations, cathinone use has increased with the first cases seen in 2010. Opiates/opioids are the main co-ingested drugs of abuse. The pattern of cathinone use shifted from methylone in 2010/2011 to 3,4-methylenedioxypyrovalerone (MDPV) and 3-methylmethcathinone (3-MMC) in 2014/2015. We conclude that in our setting "typical" cathinone users are males in their thirties. They are seldom drug naïve and regularly co-ingest illicit drugs. Preventive measures have to be tailored to these difficult to reach patients. Present efforts to educate young clubbers in their late teens may fail to reach the pertinent demographic.
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http://dx.doi.org/10.1080/15563650.2017.1301463DOI Listing
July 2017

L-Arginine in the treatment of valproate overdose - five clinical cases.

Clin Toxicol (Phila) 2017 04 3;55(4):260-266. Epub 2017 Feb 3.

a Department of Clinical Toxicology , Klinikum Rechts der Isar, Technical University of Munich (TUM) , Munich , Germany.

Background: Valproic acid and its metabolites - particularly valproyl-CoA - are inhibitors of the enzyme N-acetylglutamate synthetase. The amino acid l-arginine can stimulate N-acetylglutamate synthetase activity and could be potentially used therapeutically to correct hyperammonemia caused by valproate therapy or overdose. Severely valproic-acid-poisoned patients are usually treated with l-carnitine or hemodialysis in order to decrease hyperammonemia. We herein report of five cases, in which l-arginine was administered.

Methods: Observational study on five cases. Patients with hyperammonemia (i.e., ammonia 80 > μg/dL) and symptoms consistent with valproate overdose (i.e., drowsiness, coma) were selected for treatment with l-arginine. Data was collected retrospectively.

Results: l-Arginine decreased ammonia levels in a close temporal relation (case I ammonia in EDTA-plasma [μg/dL] decreased from 381 to 39; case II from 281 to 50; case III from 669 to 74; case IV from 447 to 56; case V from 202 to 60). In cases I and II, hemodialysis was performed and l-carnitine was given before the administration of l-arginine. In case III, hemodialysis was performed after the administration of l-arginine was already started. In cases IV and V, treatment with l-arginine was the sole measure to decrease ammonia levels in plasma.

Conclusion: The results suggest that l-arginine may be beneficial in selected cases of valproate overdose complicated by hyperammonemia. l-Arginine could extend our conventional treatment options for valproic acid overdose.
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http://dx.doi.org/10.1080/15563650.2017.1284333DOI Listing
April 2017

Effect of hemoperfusion on flecainide serum concentration - a case report.

Clin Toxicol (Phila) 2017 Feb 12;55(2):153-154. Epub 2016 Oct 12.

d Medical ICU, Department of Internal Medicine I,University of Bonn, Bonn, Germany; Toxicological ICU,Department of Clinical Toxicology , Klinikum rechts derIsar, Technical University of Munich , Munich , Germany.

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http://dx.doi.org/10.1080/15563650.2016.1241400DOI Listing
February 2017

Ideal polyethylene nanocrystals.

J Am Chem Soc 2013 Aug 26;135(31):11645-50. Epub 2013 Jul 26.

Chair of Chemical Materials Science, Department of Chemistry, University of Konstanz, Universitätsstr. 10, D-78457 Konstanz, Germany.

The water-soluble catalyst precursor [[(2,4,6-(3,5-(CF3)2C6H3)3-C6H2)-N═C(H)-(3-(9-anthryl)-2-O-C6H3)-κ(2)-N,O]Ni(CH3)(TPPTS)] (TPPTS = tri(sodiumphenylsulfonate)phosphine) polymerizes ethylene to aqueous dispersions of highly ordered nanoscale crystals (crystallinity χ(DSC) ≥ 90%) of strictly linear polyethylene (<0.7 methyl-branches/1000 carbon atoms, Mn = 4.2 × 10(5) g mol(-1)). SAXS in combination with cryo-TEM confirms this unusually high degree of order (χ(SAXS) = 82%) and shows the nanoparticles to possess a very thin amorphous layer on the crystalline lamella, just sufficient to accommodate a loop, but likely no entanglements. This ideal chain-folded structure is corroborated by annealing studies on the aqueous-dispersed nanoparticles, which show that the chain can move through the crystal as evidenced by lamella thickening without disturbing the crystalline order as concluded from an unaltered low thickness of the amorphous layers. These ideal chain-folded polyethylene nanocrystals arise from the crystallization in the confined environment of a nanoparticle and a deposition of the growing polymer chain on the crystal growth front as the chain is formed by the catalyst.
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http://dx.doi.org/10.1021/ja4052334DOI Listing
August 2013

Nonaqueous microemulsions based on n,n'-alkylimidazolium alkylsulfate ionic liquids.

Langmuir 2013 Jun 28;29(23):6833-9. Epub 2013 May 28.

Institut für Chemie, Universität Potsdam, Potsdam (Golm), Germany.

The ternary system composed of the ionic liquid surfactant (IL-S) 1-butyl-3-methylimidazolium dodecylsulfate ([Bmim][DodSO4]), the room temperature ionic liquid (RTIL) 1-ethyl-3-methylimidazolium ethylsulfate ([Emim][EtSO4]), and toluene has been investigated. Three major mechanisms guiding the structure of the isotropic phase were identified by means of conductometric experiments, which have been correlated to the presence of oil-in-IL, bicontinuous, and IL-in-oil microemulsions. IL-S forms micelles in toluene, which swell by adding RTIL as to be shown by dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS) experiments. Therefore, it is possible to form water-free IL-in-oil reverse microemulsions ≤10 nm in size as a new type of nanoreactor.
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http://dx.doi.org/10.1021/la401080qDOI Listing
June 2013

Anisotropic nanoparticles of precise microstructure polyolefins.

Chem Commun (Camb) 2012 Sep 3;48(73):9153-5. Epub 2012 Aug 3.

Department of Chemistry, University of Konstanz, Universitätsstrasse 10, D-78457 Konstanz, Germany.

Nanoparticles of precisely branched polyethylenes possess a distinct oblate shape resulting from a crystalline lamella in the particle as revealed by SAXS and TEM, and display controllable and well-behaved thermal behaviour.
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http://dx.doi.org/10.1039/c2cc32834hDOI Listing
September 2012

Is detection of bacterial DNA in ascitic fluid of clinical relevance?

Eur J Gastroenterol Hepatol 2010 Dec;22(12):1487-94

Departments of aInternal Medicine I, University of Bonn, Bonn, Germany.

Background: In patients with cirrhosis, bacterial DNA has been found in ascites reflecting bacterial translocation. However, the clinical relevance of this finding is ill-defined especially compared with the standard diagnostics for detection of spontaneous bacterial peritonitis (SBP). Furthermore, other DNA tests have not been sufficiently evaluated.

Patients And Methods: We prospectively included 151 patients with cirrhosis and ascites admitted to our department. The patients were evaluated for diagnosis of SBP (polymorphonuclear count > 250 cells/mm) or finding of bacterascites, defined by positive bacterial culture from ascites. To detect bacterial species of bacterial DNA fragments in ascites, broad-range polymerase chain reaction and nucleotide sequencing analysis with the LightCycler SeptiFast Kit Mgrade were performed. Routine parameters were correlated with these findings.

Results: Eighteen of 151 patients (12%) had SBP according to the classic definition. Bacterial DNA was detected in five of these 18 patients (3%), whereas in 13 patients (9%), bacterial DNA was detected without standard SBP. Seven patients (5%) had culture-positive SBP, only in two of them bacterial DNA was detected. In multivariate analysis, C-reactive protein (P = 0.000), white blood cell count (P = 0.019), and lactic acid dehydrogenase in ascites (P = 0.000) were independently associated with SBP. In the DNA-positive ascites group, none of the assessed parameters was significantly associated with the bacterial DNA positivity.

Conclusion: We found no correlation between detection of bacterial DNA in ascites and SBP (polymorphonuclear count > 250/mm). In contrast to the patients with bacterial DNA in ascites, patients with SBP showed clinical signs of infection. This study provides no evidence that detection of bacterial DNA in ascites of patients with liver cirrhosis is of clinical or diagnostic relevance when using the panel of LightCycler SeptiFast Kit Mgrade.
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http://dx.doi.org/10.1097/MEG.0b013e328340c43aDOI Listing
December 2010

18F-FDG-PET and histopathology in 131I-lipiodol treatment for primary liver cancer.

Cancer Biother Radiopharm 2009 Aug;24(4):445-52

Radiology and Nuclear Medicine Institute, Bad Honnef, Germany.

The diagnostic accuracy of 18F-FDG-PET (fluoro-2-deoxyglucose-positron emission tomography) remains questionable for primary hepatocellular carcinoma (HCC) but seems to be more promising for restaging and therapy control. Yet, there are no data on FDG-PET in 131I-lipiodol treatment for primary liver cancer. The aim of this study was to relate baseline FDG-PET findings to histologic data and to assess, for the first time, the role of repetitive FDG-PET imaging for follow-up of 131I-lipiodol treatment. Eighteen (18) patients (16 HCC, 2 cholangiocellular carcinoma; CCC) with 36 treatment courses (up to four per patient) had 35 PET exams, including 18 post-treatment follow-up scans in 10 patients (up to three per patient, one without baseline PET; n = 17). Histopathologic results were available in 15 patients. PET results were retrospectively related to histopathologic type, grading, presence of cirrhosis, and tumor size at baseline and compared with computed tomography (CT) during follow-up. Prior to 131I-lipiodol treatment, 8 patients were PET positive and 9 PET negative. Most of the large HCCs were PET positive and most small tumors PET negative (p < 0.05), despite an overlap below 11 cm. There was no identifiable correlation between PET results and degree of tumor differentiation. Overall, 9 of 10 patients with 17 of 18 follow-up scans showed concordant results with CT. The one discrepant case became PET negative after the first treatment course, despite CT-proven tumor growth (false negative). Patient management was not changed due to PET results. In conclusion, large HCCs were significantly more often PET positive, but there was no correlation with the degree of differentiation. Follow-up PET may be useful if the tumor is first demonstrated to be FDG positive.
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http://dx.doi.org/10.1089/cbr.2008.0560DOI Listing
August 2009

Severe respiratory failure due to diffuse alveolar hemorrhage: clinical characteristics and outcome of intensive care.

J Crit Care 2010 Jun 9;25(2):230-5. Epub 2009 Jul 9.

Medical ICU, Department of Internal Medicine I, University of Bonn, D-53105 Bonn, Germany.

Background: The aim of this study was to characterize patients and report outcome of diffuse alveolar hemorrhage (DAH) requiring intensive care unit support.

Patients And Methods: Thirty-seven patients were identified. Clinical characteristics and outcome were determined by chart review.

Results: Eighty-nine percent of patients presented with shortness of breath, 23% with cough, and 3% with hemoptysis. In 9% of patients, a diagnosis of DAH was suspected on admission. Diagnosis was confirmed by finding a progressively hemorrhagic bronchoalveolar lavage fluid in 89% and by a positive iron stain in 11% of patients. Vasculitis was causative in 19%, drug toxicity in 11%, thrombocytopenia in 27%, stem-cell transplantation in 5%, sepsis-associated lung injury in 22%, and unknown mechanisms in 16%. Thirty-two patients were mechanically ventilated, 4 received noninvasive ventilation, and 1 received supplemental oxygen therapy. Overall, 18 (49%) of 37 patients survived the intensive care unit stay. Survival was markedly different between patients with an immunologic/unknown etiology (82%) and patients with thrombocytopenia and/or sepsis (22%).

Discussion: Diffuse alveolar hemorrhage should be considered in all patients with persistent pulmonary infiltrates. Both bronchoalveolar lavage fluid and iron stain are mandatory diagnostic means. Patients with an immunologic/idiopathic pathogenetic mechanism have a relatively good prognosis, whereas the outcome in individuals with DAH secondary to cancer therapy or sepsis is poor.
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http://dx.doi.org/10.1016/j.jcrc.2009.04.009DOI Listing
June 2010

Prevention of paracentesis-induced circulatory dysfunction: midodrine vs albumin. A randomized pilot study.

Liver Int 2008 Aug 11;28(7):1019-25. Epub 2008 Apr 11.

Department of Internal Medicine I, University of Bonn, Bonn, Germany.

Background/aims: Large-volume paracentesis in patients with cirrhosis and ascites induces arterial vasodilatation and decreases effective arterial blood volume, termed paracentesis-induced circulatory dysfunction (PICD), which can be prevented by costly intravenous albumin. Vasoconstrictors, e.g. terlipressin, may also prevent PICD. The aim was to compare the less expensive vasoconstrictor midodrine, an alpha-adrenoceptor agonist, with albumin in preventing PICD.

Methods: Twenty-four patients with cirrhosis and ascites were randomly assigned to be treated with either midodrine (n=11) (12.5 mg three times per day; over 2 days) or albumin (n=13) (8 g/L of removed ascites) after large-volume paracentesis. Effective arterial blood volume was assessed indirectly by measuring plasma renin and aldosterone concentration on days 0 and 6 after paracentesis; renal function and haemodynamic changes were also measured. PICD was defined as an increase in plasma renin concentration on day 6 by more than 50% of the baseline value.

Results: PICD developed in six patients of the midodrine group (60%) and in only four patients (31%) of the albumin group. Six days after paracentesis, the aldosterone concentration increased significantly in the midodrine group, but not in the albumin group.

Conclusions: This pilot study suggests that midodrine is not as effective as albumin in preventing circulatory dysfunction after large-volume paracentesis in patients with cirrhosis and ascites.
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http://dx.doi.org/10.1111/j.1478-3231.2008.01734.xDOI Listing
August 2008

Prevention of paracentesis-induced circulatory dysfunction: midodrine vs albumin. A randomized pilot study.

Liver Int 2008 Aug 11;28(7):1019-25. Epub 2008 Apr 11.

Department of Internal Medicine I, University of Bonn, Bonn, Germany.

Background/aims: Large-volume paracentesis in patients with cirrhosis and ascites induces arterial vasodilatation and decreases effective arterial blood volume, termed paracentesis-induced circulatory dysfunction (PICD), which can be prevented by costly intravenous albumin. Vasoconstrictors, e.g. terlipressin, may also prevent PICD. The aim was to compare the less expensive vasoconstrictor midodrine, an alpha-adrenoceptor agonist, with albumin in preventing PICD.

Methods: Twenty-four patients with cirrhosis and ascites were randomly assigned to be treated with either midodrine (n=11) (12.5 mg three times per day; over 2 days) or albumin (n=13) (8 g/L of removed ascites) after large-volume paracentesis. Effective arterial blood volume was assessed indirectly by measuring plasma renin and aldosterone concentration on days 0 and 6 after paracentesis; renal function and haemodynamic changes were also measured. PICD was defined as an increase in plasma renin concentration on day 6 by more than 50% of the baseline value.

Results: PICD developed in six patients of the midodrine group (60%) and in only four patients (31%) of the albumin group. Six days after paracentesis, the aldosterone concentration increased significantly in the midodrine group, but not in the albumin group.

Conclusions: This pilot study suggests that midodrine is not as effective as albumin in preventing circulatory dysfunction after large-volume paracentesis in patients with cirrhosis and ascites.
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http://dx.doi.org/10.1111/j.1478-3231.2008.01734.xDOI Listing
August 2008

Diffuse alveolar haemorrhage in a systemic lupus erythematosus patient successfully treated with rituximab: a case report.

Nephrol Dial Transplant 2008 Jan 12;23(1):385-6. Epub 2007 Oct 12.

Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I--Allgemeine Innere Medizin, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany.

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http://dx.doi.org/10.1093/ndt/gfm701DOI Listing
January 2008

High dose chemotherapy with autologous stem cell transplantation in diffuse large B-cell lymphoma.

Ger Med Sci 2007 Jun 19;5:Doc02. Epub 2007 Jun 19.

Department of Internal Medicine I, University of Bonn, Bonn, Germany.

Background: High-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) plays an important role in the treatment of aggressive non-Hodgkin's lymphoma (NHL). We report on a retrospective analysis of all patients with diffuse large B-cell lymphoma who were consecutively treated with HDT followed by ASCT at the University Hospital of Bonn, Germany, between 1996 and 2004.

Methods: A total of 25 patients were transplanted for biopsy-proven diffuse large B-cell lymphoma (DLBCL). Eight patients received up-front HDT as first-line therapy, four patients received HDT due to incomplete response to conventional induction chemotherapy, and six patients were treated for primary refractory disease. Seven patients had recurrent lymphoma.

Results: A complete remission (CR) was achieved in 14 of 25 patients (56%). Estimated 3-year survival for patients treated with upfront HDT, chemosensitive patients with incomplete response to first line therapy, and patients with chemosensitive relapsed disease was 87.5%, 50.0% and 60.0%, respectively. In contrast, no patient with primary refractory disease or relapsed disease lacking chemosensitivity lived longer than 8 months. Chemosensitivity was the only significant prognostic factor for overall survival (OS) in multivariate analysis.

Conclusions: Our results confirm that HDT and ASCT is a highly effective therapy in patients with DLBCL leading to long-term survival in a substantial proportion of patients. Patients treated upfront for high-risk disease, incomplete response to conventional first-line therapy, or for chemosensitive relapse have a good prognosis. In contrast, patients with primary chemorefractory disease and patients with relapsed disease lacking chemosensitivity do not benefit from HDT with ASCT.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2703236PMC
June 2007

DHAP in combination with rituximab vs DHAP alone as salvage treatment for patients with relapsed or refractory diffuse large B-cell lymphoma: a matched-pair analysis.

Leuk Lymphoma 2006 Dec;47(12):2558-66

Department of Internal Medicine I, University of Bonn, Germany.

The addition of rituximab to chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) has been shown to improve outcome in first-line therapy. However, in patients with relapsed or refractory disease, the value of adding rituximab to salvage chemotherapy is less clearly defined. This study performed a matched-pair analysis of patients with relapsed or refractory DLBCL by comparing the combination of dexamethasone, high-dose cytarabine and cisplatin (DHAP) with rituximab to DHAP alone. Sixty-seven patients with relapsed or refractory DLBCL were collected from two prospective phase II trials from Germany and Italy. Twenty-three patient pairs treated with either DHAP in combination with rituximab or DHAP alone could be analysed after matching for important prognostic factors. The addition of rituximab to the DHAP regimen led to higher complete and similar overall remission rates. However, differences with regard to complete remission rates failed to reach statistical significance, thereby necessitating further evaluation of the role of combined immunochemotherapy in this patient population.
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http://dx.doi.org/10.1080/10428190600926572DOI Listing
December 2006

Dexamethasone, high-dose cytarabine, and cisplatin in combination with rituximab as salvage treatment for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma.

Cancer Invest 2006 Oct;24(6):593-600

Department of Internal Medicine I, University of Bonn, Germany.

We designed a multicenter Phase II trial to prospectively evaluate the efficacy and safety of the combination of rituximab with the DHAP regimen (dexamethasone, high-dose cytarabine, cisplatin) in patients who relapsed after or were resistant to a CHOP-like regimen. A total of 53 patients with relapsed or resistant aggressive B-cell NHL were analyzed. The overall response rate was 62.3 percent. With a median follow-up of 24.9 months, median overall and progression-free survivals were 8.5 and 6.7 months, respectively. Immunochemotherapy with rituximab and DHAP proved to be feasible and effective in this patient population.
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http://dx.doi.org/10.1080/07357900600814490DOI Listing
October 2006
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