Publications by authors named "Peter Steiger"

32 Publications

Cutaneous and systemic hyperinflammation drives maculopapular drug exanthema in severely ill COVID-19 patients.

Allergy 2021 Jun 22. Epub 2021 Jun 22.

Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.

Background: Coronavirus disease-2019 (COVID-19) has been associated with cutaneous findings, some being the result of drug hypersensitivity reactions such as maculopapular drug rashes (MDR). The aim of this study was to investigate whether COVID-19 may impact the development of the MDR.

Methods: Blood and skin samples from COVID-19 patients (based on a positive nasopharyngeal PCR) suffering from MDR (COVID-MDR), healthy controls, non-COVID-19-related patients with drug rash with eosinophilia and systemic symptoms (DRESS), and MDR were analyzed. We utilized imaging mass cytometry (IMC) to characterize the cellular infiltrate in skin biopsies. Furthermore, RNA sequencing transcriptome of skin biopsy samples and high-throughput multiplexed proteomic profiling of serum were performed.

Results: IMC revealed by clustering analyses a more prominent, phenotypically shifted cytotoxic CD8 T cell population and highly activated monocyte/macrophage (Mo/Mac) clusters in COVID-MDR. The RNA sequencing transcriptome demonstrated a more robust cytotoxic response in COVID-MDR skin. However, severe acute respiratory syndrome coronavirus 2 was not detected in skin biopsies at the time point of MDR diagnosis. Serum proteomic profiling of COVID-MDR patients revealed upregulation of various inflammatory mediators (IL-4, IL-5, IL-6, TNF, and IFN-γ), eosinophil and Mo/Mac -attracting chemokines (MCP-2, MCP-3, MCP-4 and CCL11). Proteomics analyses demonstrated a massive systemic cytokine storm in COVID-MDR compared with the relatively milder cytokine storm observed in DRESS, while MDR did not exhibit such features.

Conclusion: A systemic cytokine storm may promote activation of Mo/Mac and cytotoxic CD8 T cells in severe COVID-19 patients, which in turn may impact the development of MDR.
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http://dx.doi.org/10.1111/all.14983DOI Listing
June 2021

Prevalence and outcome of silent hypoxemia in COVID-19.

Minerva Anestesiol 2021 03;87(3):325-333

Department of Anesthesiology, Intensive Care and Emergency Medicine, Medical University of Göttingen, Göttingen, Germany.

Background: In the early stages of COVID-19 pneumonia, hypoxemia has been described in absence of dyspnea ("silent" or "happy" hypoxemia). Our aim was to report its prevalence and outcome in a series of hypoxemic patients upon Emergency Department admission.

Methods: In this retrospective observational cohort study we enrolled a study population consisting of 213 COVID-19 patients with PaO2/FiO2 ratio <300 mmHg at hospital admission. Two groups (silent and dyspneic hypoxemia) were defined. Symptoms, blood gas analysis, chest X-ray (CXR) severity, need for intensive care and outcome were recorded.

Results: Silent hypoxemic patients (68-31.9%) compared to the dyspneic hypoxemic patients (145-68.1%) showed greater frequency of extra respiratory symptoms (myalgia, diarrhea and nausea) and lower plasmatic LDH. PaO2/FiO2 ratio was 225±68 mmHg and 192±78 mmHg in silent and dyspneic hypoxemia respectively (P=0.002). Eighteen percent of the patients with PaO2/FiO2 from 50 to 150 mmHg presented silent hypoxemia. Silent and dyspneic hypoxemic patients had similar PaCO2 (34.2±6.8 mmHg vs. 33.5±5.7 mmHg, P=0.47) but different respiratory rates (24.6±5.9 bpm vs. 28.6±11.3 bpm respectively, P=0.002). Even when CXR was severely abnormal, 25% of the population was silent hypoxemic. Twenty-six point five percent and 38.6% of silent and dyspneic patients were admitted to the ICU respectively (P=0.082). Mortality rate was 17.6% and 29.7% (log-rank P=0.083) in silent and dyspneic patients.

Conclusions: Silent hypoxemia is remarkably present in COVID-19. The presence of dyspnea is associated with a more severe clinical condition.
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http://dx.doi.org/10.23736/S0375-9393.21.15245-9DOI Listing
March 2021

Maternal effects on reproduction in the precocial European hare (Lepus europaeus).

PLoS One 2021 17;16(2):e0247174. Epub 2021 Feb 17.

Institute of Wildlife Biology and Game Management, University of Natural Resources and Life Sciences, Vienna, Austria.

In female mammals, reproduction, and in particular lactation, is the energetically most exigent life-history phase. Reproduction is strongly controlled by body reserves and food availability, so females with better body condition or food supply are believed to have higher reproductive output. Additionally, the growth and mortality of young mammals depends on their postnatal development. Therefore, the degree of precociality affects energetic demands for both mothers and young. To study the reproductive performance of the precocial European hare (Lepus europaeus), we analysed relationships between six predictor variables describing maternal and environmental effects and nine response variables relating to reproduction from 217 captive females. We compared the data with those of precocial and altricial mammal species from an extensive literature search. For hares, we found: (1) Heavier females had heavier litters at birth. (2) In summer and spring, total litter mass was larger than in winter. (3) At the end of lactation, the litters of multiparous females were heavier than those of primiparous females. (4) Both older females and females giving birth for the first time had relatively high leveret mortality during lactation. Comparing our results with the literature for other mammals revealed that the body condition (i.e., body mass) of females before birth is predictive of reproductive parameters in both precocial and altricial species. In the precocial hare, female body condition is no longer predictive of reproductive parameters at the end of lactation, whereas in altricial species, female body condition remains predictive of reproduction (litter mass at the end of lactation, offspring mortality) until the end of lactation. We conclude that these effects are caused by precocial offspring feeding on solid food soon after birth and, thus, being less dependent on the mother's body condition during lactation than altricial offspring. In line with this, precociality might have evolved as a way of buffering offspring against maternal effects.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247174PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888652PMC
February 2021

Intracerebral endotheliitis and microbleeds are neuropathological features of COVID-19.

Neuropathol Appl Neurobiol 2021 04 14;47(3):454-459. Epub 2020 Dec 14.

Institute of Neuropathology, University of Zurich, Zurich, Switzerland.

Coronavirus disease 19 (COVID-19) is a rapidly evolving pandemic caused by the coronavirus Sars-CoV-2. Clinically manifest central nervous system symptoms have been described in COVID-19 patients and could be the consequence of commonly associated vascular pathology, but the detailed neuropathological sequelae remain largely unknown. A total of six cases, all positive for Sars-CoV-2, showed evidence of cerebral petechial hemorrhages and microthrombi at autopsy. Two out of six patients showed an elevated risk for disseminated intravascular coagulopathy according to current criteria and were excluded from further analysis. In the remaining four patients, the hemorrhages were most prominent at the grey and white matter junction of the neocortex, but were also found in the brainstem, deep grey matter structures and cerebellum. Two patients showed vascular intramural inflammatory infiltrates, consistent with Sars-CoV-2-associated endotheliitis, which was associated by elevated levels of the Sars-CoV-2 receptor ACE2 in the brain vasculature. Distribution and morphology of patchy brain microbleeds was clearly distinct from hypertension-related hemorrhage, critical illness-associated microbleeds and cerebral amyloid angiopathy, which was ruled out by immunohistochemistry. Cerebral microhemorrhages in COVID-19 patients could be a consequence of Sars- CoV-2-induced endotheliitis and more general vasculopathic changes and may correlate with an increased risk of vascular encephalopathy.
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http://dx.doi.org/10.1111/nan.12677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753688PMC
April 2021

Safety of enzymatic debridement in extensive burns larger than 15% total body surface area.

Burns 2021 Jun 25;47(4):796-804. Epub 2020 Oct 25.

Department of Plastic and Hand Surgery, Burn Center, University Hospital Zurich, Zurich, Switzerland.

Objectives: Bromelain-based enzymatic debridement has emerged as an alternative to surgical eschar removal. Indications include partial thickness, mixed pattern, and full-thickness burns. Enzymatic debridement has been approved by the European Medicines Agency for treating burn wounds affecting <15% total body surface area (TBSA). Data and evidence for the treatment of areas >15% TBSA in one session is scarce. The aim of this retrospective study was to retrospectively analyze off-label use of enzymatic debridement in a single burn center for large TBSA burns.

Methods: Between 01/2017 and 12/2018, 59 patients with partial- to full-thickness burns underwent enzymatic debridement in a single center study. Patients were categorized into two groups: the regular use group with a treated area less than 15% TBSA and the off-label group (OG) with larger TBSA debrided in one session. Treatment was evaluated for systemic inflammatory reaction, bleeding, hemodynamic instability and electrolyte shifts.

Results: In total, 49 patients were treated in the regular use group with a median application area of 6% (IQR 2.5-9.5) and 10 patients were treated in the off-label group with a median application area of 18% (IQR 15-19) TBSA. We found no significant differences regarding blood pressure, body temperature or hemodynamic stability during and after enzymatic debridement. No treatment-related serious adverse events were observed in either group. Catecholamine use was similar in both groups. No differences in leukocyte counts, CRP, PCT and lactate prior to application and during the following three days were observed. Sodium, potassium, chloride and phosphate levels did not differ. We found no evidence of an electrolyte shift. Survival was 49 of 49 patients (100%) in the RG and 7 of 10 patients (70%) in the OG (p = 0.004).

Conclusion: Enzymatic debridement did not result in any expected or unexpected side effects in the patient groups investigated. These preliminary results indicate the potential safety of bromelain-based enzymatic debridementin the treatment of burns greater than 15% TBSA.
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http://dx.doi.org/10.1016/j.burns.2020.10.012DOI Listing
June 2021

Large and Small Cerebral Vessel Involvement in Severe COVID-19: Detailed Clinical Workup of a Case Series.

Stroke 2020 12 15;51(12):3719-3722. Epub 2020 Oct 15.

Neuroimmunology and Multiple Sclerosis Research Section (A.L., I.J.), University Hospital and University of Zurich, Switzerland.

Background And Purpose: Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms.

Methods: We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement. Patients identified underwent computed tomography, magnetic resonance imaging, electroencephalography, cerebrospinal fluid analysis, and autopsy in case of death.

Results: Of 32 critically ill patients with COVID-19, 8 (25%) had severe central nervous system involvement. Two presented with lacunar ischemic stroke in the early phase and 6 with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in 3 with additional subarachnoid hemorrhage and in 2 with additional small ischemic lesions. In 3 patients, intracranial vessel wall sequence magnetic resonance imaging was performed for the first time to our knowledge. All showed contrast enhancement of vessel walls in large cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. Reverse transcription-polymerase chain reactions for SARS-CoV-2 in cerebrospinal fluid were all negative. No intrathecal SARS-CoV-2-specific IgG synthesis was detectable.

Conclusions: Different mechanisms of cerebrovascular disorders might be involved in COVID-19. Acute ischemic stroke might occur early. In a later phase, microinfarctions and vessel wall contrast enhancement occur, indicating small and large cerebral vessels involvement. Central nervous system disorders associated with COVID-19 may lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.
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http://dx.doi.org/10.1161/STROKEAHA.120.031224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678671PMC
December 2020

Benralizumab for severe DRESS in two COVID-19 patients.

J Allergy Clin Immunol Pract 2021 01 8;9(1):481-483.e2. Epub 2020 Oct 8.

Faculty of Medicine, University of Zurich, Zurich, Switzerland; Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; Department of Dermatology, Hochgebirgsklinik Davos, Davos, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.09.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543785PMC
January 2021

Indications and contraindications for extracorporeal life support for severe heart or lung failure: a systematic review.

Minerva Anestesiol 2021 02 4;87(2):199-209. Epub 2020 Aug 4.

Clinical Ethics Unit, Institute of Biomedical Ethics and History of Medicine, Zurich University Hospital, University of Zurich, Zurich, Switzerland.

Introduction: The effectiveness of extracorporeal life support (ECLS) in critically ill patients remains unclear despite a substantial increase in its use. This study critically assesses existing ECLS guidelines, consensus statements, and position papers to systematically review them for agreements and differences regarding indications and contraindications for ECLS.

Evidence Acquisition: The aims of this review were to identify available indications and contraindications for ECLS and to evaluate the quality of the evidence on which they are based. Documents containing recommendations regarding indications and/or contraindications for ECLS in adults (aged 18+) were identified through Medline, EMBASE, and CENTRAL searches. Additional documents were identified from guideline-specific databases and the internet websites of professional societies. Based on the Appraisal of Guidelines for Research and Evaluation (AGREE II), four independent reviewers assessed the rigor of development and quality of the documents.

Evidence Synthesis: Eleven documents met the inclusion criteria. Three documents received an average score of ≥50% in all domains. However, the Editorial independence domain only scored <50% in most of the documents. Overall, 13 cardiac and 13 pulmonary ECLS indications, and 23 cardiac and 14 pulmonary contraindications were identified. Indications and contraindications for ECLS use are variable across the documents included and leave considerable room for interpretation.

Conclusions: The documents included for review show considerable variability, with little consensus on indications and contraindications. This lack of consensus may reflect a lack of clarity regarding ECLS utility. Additionally, it may reveal the necessity for individualized, patient-dependent criteria supported by the best evidence available.
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http://dx.doi.org/10.23736/S0375-9393.20.14513-9DOI Listing
February 2021

Myocardial edema in COVID-19 on cardiac MRI.

J Heart Lung Transplant 2020 07 28;39(7):730-732. Epub 2020 May 28.

Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

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http://dx.doi.org/10.1016/j.healun.2020.04.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834291PMC
July 2020

Electron microscopy of SARS-CoV-2: a challenging task - Authors' reply.

Lancet 2020 05 19;395(10238):e100. Epub 2020 May 19.

Department of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(20)31185-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237177PMC
May 2020

Endothelial cell infection and endotheliitis in COVID-19.

Lancet 2020 05 21;395(10234):1417-1418. Epub 2020 Apr 21.

Department of Pathology and Molecular Pathology, University Hospital Zurich, CH-8091 Zurich, Switzerland.

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http://dx.doi.org/10.1016/S0140-6736(20)30937-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172722PMC
May 2020

Implementation of a multiprofessional, multicomponent delirium management guideline in two intensive care units, and its effect on patient outcomes and nurse workload: a pre-post design retrospective cohort study.

Swiss Med Wkly 2020 Jan 27;150:w20185. Epub 2020 Jan 27.

Intensive Care Unit, Department of Intensive Care Medicine, University Hospital Basel, Switzerland.

Aim Of The Study: Delirium is a frequent intensive care unit (ICU) complication, affecting 26% to 80% of ICU patients, often with serious consequences. This study aimed to evaluate the effectiveness, costs and benefits of following a standardised multiprofessional, multicomponent delirium guideline on eight outcomes: delirium prevalence and duration, lengths of stay in ICU and hospital, in-hospital mortality, duration of mechanical ventilation, and cost and nursing hours per case. It also aimed to explore the associations of delirium with length of ICU stay, length of hospital stay and duration of mechanical ventilation.

Methods: This retrospective cohort study used a pre-post design. ICU patients in an historical control group (n = 1608) who received standard ICU care were compared with a postintervention group (n = 1684) who received standardised delirium management – delirium risk identification, preventive measures, screening and treatment – with regard to eight outcomes. The delirium management guideline was developed and implemented in 2012 by a group of experts from the study hospital. As appropriate, descriptive statistics and multivariate, multilevel models were used to compare the two groups and to explore the association between delirium occurrence and the selected outcomes.

Results: Twelve percent of the 1608 historical controls and 20% of the 1684 postintervention patients were diagnosed with delirium according to the ICD-10 delirium diagnosis codes. Patients being treated for heart disease, and those with septic shock, ARDS, renal insufficiency (acute or chronic), older age and higher numbers of comorbidities were significantly more likely to develop delirium during their stay. Multivariate models comparing the historical controls with the post intervention group indicated significant differences in delirium period prevalence (odds ratio 1.68, 95% confidence interval [CI] 1.38–2.06; p <0.001), length of stay in the ICU (time ratio [TR] 0.94, CI 0.89–1.00; p = 0.048), cost per case (median difference 3.83, CI 0.54–7.11; p = 0.023) and duration of mechanical ventilation (TR 0.84, CI 0.77–0.92; p <0.001). The observed differences in the other four outcomes – in-hospital mortality, delirium duration, length of stay in the hospital, and nursing hours per case – were not significant. Delirium was a significant predictor for prolonged duration of mechanical ventilation and for both ICU and hospital stay.

Conclusion: Standardised delirium management, specifically delirium screening, supports timely detection of delirium in ICU patients. Increased awareness of delirium after the implementation of standardised multiprofessional, multicomponent management leads to increased therapeutic attention, a prolongation of ICU stay and increased costs, but with no influence on mortality.
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http://dx.doi.org/10.4414/smw.2020.20185DOI Listing
January 2020

Pancreatic Stone Protein Predicts Sepsis in Severely Burned Patients Irrespective of Trauma Severity: A Monocentric Observational Study.

Ann Surg 2020 Jan 14. Epub 2020 Jan 14.

Department of Plastic Surgery and Hand Surgery, Burn Center, University Hospital Zurich, Zurich, Switzerland.

Objective: The burn victim's inherent state of hyperinflammation frequently camouflages septic events delaying the initiation of targeted intensive care therapy. Accurate biomarkers are urgently needed to support sepsis detection before patients' clinical deterioration.

Summary Of Background Data: Evidence on the usefulness of pancreatic stone protein (PSP) as a powerful diagnostic and prognostic marker in critically ill patients has recently accumulated.

Methods: Analysis of biomarker kinetics (PSP, routine markers) was performed on 90 patients admitted to the Zurich Burn Center between May 2015 and October 2018 with burns ≥15% total body surface area with regard to infection and sepsis (Sepsis-3) over a 14-day time course.

Results: PSP differentiated between sepsis, infection and sterile inflammation from day 3 onward with an area under the curve of up to 0.89 (P < 0.001), therefore, competing with procalcitonin (area under the curve = 0.86, P < 0.001). Compared to routine inflammatory biomarkers, only PSP demonstrated a significant interaction between time and presence of sepsis - signifying a steeper increase in PSP levels in septic patients as opposed to those exhibiting a nonseptic course (interaction P < 0.001). Event-related analysis demonstrated tripled PSP serum levels within 72 hours and doubled levels within 48 hours before a clinically apparent sepsis.

Conclusion: PSP is able to differentiate between septic and nonseptic patients during acute burn care. Its steep rise up to 72 hours before clinically overt deterioration has the potential for physicians to timely initiate treatment with reduced mortality and costs.
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http://dx.doi.org/10.1097/SLA.0000000000003784DOI Listing
January 2020

Impact of allogeneic blood transfusions on clinical outcomes in severely burned patients.

Burns 2020 08 19;46(5):1083-1090. Epub 2019 Dec 19.

Department of Plastic Surgery and Hand Surgery, Burn Center, University and University Hospital Zurich, Zurich, Switzerland. Electronic address:

Background: Allogeneic blood transfusions are common in the treatment of severely burned patients as surgery may lead to major blood loss. However, transfusions are associated with a number of adverse events. Therefore, the purpose of our study was to investigate the impact of allogeneic blood transfusions on clinical outcomes in severely burned patients.

Methods: This retrospective study included all adult patients admitted to the burn center of the University Hospital Zurich between January 2004 and December 2014, with burn injuries greater than 10% of total body surface area and receiving both surgical and intensive care treatment. Primary Endpoints were infectious or thromboembolic complications and mortality and secondary endpoints were length of hospital and ICU stay. Simple and multivariable logistic and linear regression models, adjusted for injury severity and confounders, were applied.

Results: 413 patients met inclusion criteria of which 212 patients (51%) received allogenic blood products. After adjustment for injury severity and confounders, red blood cell transfusion was independently associated with wound infection (OR 13.5, 95% CI 1.7-107, p = 0.014), sepsis (OR 8.3, 4.2-16.3; p < 0.001), pneumonia (OR 4.7, 2.2-10.0; p < 0.001), thrombosis (OR 3.0, 1.2-7.4; p = 0.015), central line infection (OR 34.7, 4.6-260; p = 0.001) and a longer ICU and hospital stay (difference 17.7, CI 12.1-23.4, p < 0.001 and 22.0, 15.8-28.2, p < 0.001, respectively). Fresh frozen plasma transfusion was independently associated with a longer ICU and hospital stay (difference 13.7, 95% CI 5.5-21.8, p = 0.001 and 13.5, 4.6-22.5, p = 0.003, respectively). Platelet transfusion was independently associated with systemic inflammatory response syndrome (OR 4.5, 1.3-15.5; p = 0.018) and mortality (OR 5.8, 2.1-16.0; p = 0.001).

Conclusion: Transfusion of allogeneic blood products is associated with an increased infection rate and thromboembolic morbidity and a longer hospital stay in severely burned patients.
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http://dx.doi.org/10.1016/j.burns.2019.11.005DOI Listing
August 2020

Cerebral metabolism is not affected by moderate hyperventilation in patients with traumatic brain injury.

Crit Care 2019 Feb 13;23(1):45. Epub 2019 Feb 13.

Institute for Intensive Care Medicine, University Hospital of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.

Background: Hyperventilation-induced hypocapnia (HV) reduces elevated intracranial pressure (ICP), a dangerous and potentially fatal complication of traumatic brain injury (TBI). HV decreases the arteriolar diameter of intracranial vessels, raising the risk of cerebral ischemia. The aim of this study was to characterize the effects of moderate short-term HV in patients with severe TBI by using concomitant monitoring of cerebral metabolism, brain tissue oxygen tension (PbrO), and cerebral hemodynamics with transcranial color-coded duplex sonography (TCCD).

Methods: This prospective trial was conducted between May 2014 and May 2017 in the surgical intensive care unit (ICU) at the University Hospital of Zurich. Patients with nonpenetrating TBI older than 18 years of age with a Glasgow Coma Scale (GCS) score < 9 at presentation and with ICP monitoring, PbrO, and/or microdialysis (MD) probes during ICU admission within 36 h after injury were included in our study. Data collection and TCCD measurements were performed at baseline (A), at the beginning of moderate HV (C), after 50 min of moderate HV (D), and after return to baseline (E). Moderate HV was defined as arterial partial pressure of carbon dioxide 4-4.7 kPa. Repeated measures analysis of variance was used to compare variables at the different time points, followed by post hoc analysis with Bonferroni adjustment as appropriate.

Results: Eleven patients (64% males, mean age 36 ± 14 years) with an initial median GCS score of 7 (IQR 3-8) were enrolled. During HV, ICP and mean flow velocity (CBFV) in the middle cerebral artery decreased significantly. Glucose, lactate, and pyruvate in the brain extracellular fluid did not change significantly, whereas PbrO showed a statistically significant reduction but remained within the normal range.

Conclusion: Moderate short-term hyperventilation has a potent effect on the cerebral blood flow, as shown by TCCD, with a concomitant ICP reduction. Under the specific conditions of this study, this degree of hyperventilation did not induce pathological alterations of brain metabolites and oxygenation.

Trial Registration: NCT03822026 . Registered on 30 January 2019.
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http://dx.doi.org/10.1186/s13054-018-2304-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375161PMC
February 2019

How Can Radiomics Be Consistently Applied across Imagers and Institutions?

Radiology 2019 Apr 29;291(1):60-61. Epub 2019 Jan 29.

From the Department of Scientific and Medical Services, Parexel Informatics, Parexel International, 2 Federal St, Billerica, MA 01820.

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http://dx.doi.org/10.1148/radiol.2019190051DOI Listing
April 2019

[Burn wound treatment through enzymatic debridement: First experience in Switzerland].

Handchir Mikrochir Plast Chir 2019 Apr 26;51(2):80-85. Epub 2018 Apr 26.

Klinik für Plastische Chirurgie und Handchirurgie, Zentrum für Brandverletzte, UniversitätsSpital Zürich.

Introduction: Thermal injuries are frequent and can be associated with relevant morbidity and mortality in severe cases. Excisional debridement followed by autografting is the standard of care for deep burns, but is associated with serious potential complications. Clinical results of a novel enzymatic debridement based on Bromelain raw material extracted from the pineapple plant (Nexobrid™) were published in 2014. At the Center for Burns at the University Hospital Zürich enzymatic debridement was introduced in 2016. Our experience and interpretation of the first 12 cases are reported.

Patients And Methods: Patients of at least 18 years of age with second and third degree burns were included in this study. Pregnant or breast feeding women were excluded. After so-called "pre-soaking" with saline solution, the Nexobrid™ gel was applied for 4 hours with occlusive sealing. After abrasion of the debris, "post-soaking" with Prontosan followed and definite wound dressings were applied.

Results: The mean age of the patients was 51 (19-78) years, the length of hospital stay was 38 (1-92) days. The amount of burns was 25 (1-67) % of the total body surface area (TBSA). On average, 11 (1-18) % of the TBSA was debrided with Nexobrid™ after 7 (1-19) days. In 8 patients, the defects completely healed without scarring after Nexobrid™ treatment. In 4 patients additional surgical measures were necessary to complete the debridement as well as to cover the defect. The treatment with Nexobrid™ was efficient in difficult treatment areas such as back, hands and feet, where preservation of the demis prevented joint contracture through scarring.

Conclusion: Treatment with Nexobrid™ extends the armamentarium to treat partial second-degree thermal injuries with good long-term results. It can be applied in analgosedation in an intensive care setting and reduces the need for surgical treatment.
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http://dx.doi.org/10.1055/s-0044-100613DOI Listing
April 2019

Low Level of Vegetative State After Traumatic Brain Injury in a Swiss Academic Hospital.

Anesth Analg 2018 09;127(3):698-703

Surgical Intensive Care Unit.

Background: No standards exist regarding decision making for comatose patients, especially concerning life-saving treatments. The aim of this retrospective, single-center study was to analyze outcomes and the decision-making process at the end of life (EOL) in patients with traumatic brain injury (TBI) in a Swiss academic tertiary care hospital.

Methods: Consecutive admissions to the surgical intensive care unit (ICU) with stays of at least 48 hours between January 1, 2012 and June 30, 2015 in patients with moderate to severe TBI and with fatality within 6 months after trauma were included. Descriptive statistics were used.

Results: Of 994 ICU admissions with TBI in the study period, 182 had an initial Glasgow Coma Scale <13 and a length of stay in the ICU >48 hours. For 174 of them, a 6-month outcome assessment based on the Glasgow Outcome Scale (GOS) was available: 43.1% (36.0%-50.5%) had favorable outcomes (GOS 4 or 5), 28.7% (22.5%-35.9%) a severe disability (GOS 3), 0.6% (0%-3.2%) a vegetative state (GOS 2), and 27.6% (21.5%-34.7%) died (GOS 1). Among the GOS 1 individuals, 45 patients had a complete dataset (73% men; median age, 67 years; interquartile range, 43-79 years). Life-prolonging therapies were limited in 95.6% (85.2%-99.2%) of the cases after interdisciplinary prognostication and involvement of the surrogate decision maker (SDM) to respect the patient's documented or presumed will. In 97.7% (87.9%-99.9%) of the cases, a next of kin was the SDM and was involved in the EOL decision and process in 100% (96.3%-100.0%) of the cases. Written advance directives (ADs) were available for 14.0% (6.6%-27.3%) of the patients, and 34.9% (22.4%-49.8%) of the patients had shared their EOL will with relatives before trauma. In the other cases, each patient's presumed will was acknowledged after a meeting with the SDM and was binding for the EOL decision.

Conclusions: At our institution, the majority of deaths after TBI follow a decision to limit life-prolonging therapies. The frequency of patients in vegetative state 6 months after TBI is lower than expected; this could be due to the high prevalence of limitation of life-prolonging therapies. EOL decision making follows a standardized process, based on patients' will documented in the ADs or on preferences assumed by the SDM. The prevalence of ADs was low and should be encouraged.
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http://dx.doi.org/10.1213/ANE.0000000000003375DOI Listing
September 2018

Effect of diagnosis related groups implementation on the intensive care unit of a Swiss tertiary hospital: a cohort study.

BMC Health Serv Res 2018 02 5;18(1):84. Epub 2018 Feb 5.

Institute of Intensive Care Medicine, University Hospital Zurich, University Zurich, Raemistrasse 100, CH-8091, Zurich, Switzerland.

Background: In 2013 the Swiss Diagnosis Related Groups ((Swiss)-DRG) was implemented in Intensive Care Units (ICU). Its impact on hospitalizations has not yet been examined. We compared the number of ICU admissions, according to clinical severity and referring institution, and screened whether implementation of Swiss-DRG affected admission policy, ICU length-of-stay (ICU-LOS) or ICU mortality.

Methods: Retrospective, single centre, cohort study conducted at the University Hospital Zurich, Switzerland between January 2009 and end of September 2013. Demographic and clinical data was retrieved from a quality assurance database.

Results: Admissions (n = 17,231) before the introduction of Swiss-DRG were used to model expected admissions after DRG, and then compared to the observed admissions. Forecasting matched observations in patients with a high clinical severity admitted from internal units and external hospitals (admitted / predicted: 709 / 703, [95% Confidence Interval (CI), 658-748] and 302 / 332, [95% CI, 269-365] respectively). In patients with low severity of disease, in-house admissions became more frequent than expected and external admission were less frequent (admitted / predicted: 1972 / 1910, [95% CI, 1898-1940] and 436 / 518, [95% CI, 482-554] respectively). Various mechanisms related to Swiss-DRG may have led to these changes. DRG could not be linked to significant changes in regard to ICU-LOS and ICU mortality.

Conclusions: DRG introduction had not affected ICU admissions policy, except for an increase of in-house patients with a low clinical severity of disease. DRG had neither affected ICU mortality nor ICU-LOS.
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http://dx.doi.org/10.1186/s12913-018-2869-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800035PMC
February 2018

Neurologic Injury With Severe Adult Respiratory Distress Syndrome in Patients Undergoing Extracorporeal Membrane Oxygenation: A Single-Center Retrospective Analysis.

Anesth Analg 2017 11;125(5):1544-1548

From the *Surgical Intensive Care Unit and †Medical Intensive Care Unit, University Hospital of Zurich, Zurich, Switzerland; ‡Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milano, Italy; and Departments of §Neuropathology and ‖Neurology, University Hospital of Zurich, Zurich, Switzerland.

This retrospective single-center study investigated the incidence of neurologic injury as determined by autopsy or cerebral imaging in 74 patients undergoing extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome. Seventy-three percent of patients were treated with venovenous and 27% with venoarterial ECMO. ECMO-associated intracerebral hemorrhage was diagnosed in 10.8% of patients. There were no cases of ischemic stroke. Clinical characteristics did not differ between patients with and without neurologic injury. Six-month survival was 13% (Wilson confidence interval, 2%-47%) in patients with severe intracerebral hemorrhage compared to an overall survival rate of 57% (Wilson confidence interval, 45%-67%).
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http://dx.doi.org/10.1213/ANE.0000000000002431DOI Listing
November 2017

Age-related outcome of patients after traumatic brain injury: a single-center observation.

Minerva Anestesiol 2017 Nov 22;83(11):1169-1177. Epub 2017 Jun 22.

Unit of Surgical Intensive Care, University Hospital of Zurich, Zurich, Switzerland -

Background: The purpose of the present study was to analyze clinical features of patients with traumatic brain injury (TBI), their age-related outcomes and determinants of long-term outcome.

Methods: This retrospective cohort study was conducted in a level I University Swiss trauma center. Consecutive patients with moderate to severe TBI admitted for more than 48 hours to the Intensive Care Unit (ICU) were included. Patients' and trauma characteristics, management during ICU stay, prognostic scores and long-term outcomes were analyzed.

Results: Hundred-seventy-four patients (72% males, mean age 49 years) were divided in three age groups: young (≤39 years, N.=69, 39.7%), middle aged (40-64 years, N.=55, 31.6%), and elderly (≥65 years, N.=50, 28.7%). In elderly patients, falls (62%) were the most common cause of TBI. Overall ICU mortality was 15% with no difference among age groups. Within six-months after TBI, 80% of elderly patients presented unfavorable outcomes. Age, pre-existing cardiovascular disease, use of anticoagulants and/or antiplatelet agents, abnormal pupillary reactivity, a high score in Marshall CT classification, and a higher glucose level were associated with unfavorable outcomes in a univariable logistic regression. In a multivariable logistic regression, age and abnormal pupillary reactivity were identified as independent risk factors for unfavorable outcomes, while presence of epidural hematoma and higher hemoglobin levels were predictors for favorable outcomes.

Conclusions: Older patients are at higher risk for long-term unfavorable outcomes than younger patients. Use of anticoagulants and/or antiplatelet agents and lower hemoglobin levels during rescue phase are associated with unfavorable long-term outcomes. Fall prevention in the elderly should be a key target of intervention programs.
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http://dx.doi.org/10.23736/S0375-9393.17.11837-7DOI Listing
November 2017

The impact of mild induced hypothermia on the rate of transfusion and the mortality in severely injured patients: a retrospective multi-centre study.

Eur J Med Res 2016 Oct 6;21(1):37. Epub 2016 Oct 6.

Division of Trauma Surgery, University Hospital Zurich, University of Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.

Background: Although under discussion, induced hypothermia (IH) is an established therapy for patients with cardiac arrest or traumatic brain injuries. The influences on coagulopathy and bleeding tendency in severely injured patients (SIP) with concomitant traumatic brain injury are most widely unclear. Therefore, the aim of this study was to quantify the effect of mild IH in SIP with concomitant severe traumatic brain injuries on transfusion rate and mortality.

Methods: In this retrospective multi-centre study, SIP from three European level-1 trauma centres with an ISS ≥16 between 2009 and 2011 were included. At hospital A, patients qualified for IH with age ≤70 years and a severe head injury with an abbreviated injury scale (AIS) of ≥3. IH was defined as target core body temperature of 35 °C. Hypothermic patients were matched with two patients, one from hospital B and one from hospital C using age and AIS. The effect of IH on the transfusion rate, complications and mortality was quantified with 95 % confidence intervals (CI). Patients not treated with IH in hospital A and those from hospital B and C, who were not matched, were used to adjust the CI for the effect of inter-hospital therapy protocol differences.

Results: Mean age of patients in the IH-group (n = 43) was 35.7 years, mean ISS 30 points and sex distribution showed 83.7 % male. Mean age of matched patients in the normotherm-group (n = 86) was 36.7 years, mean ISS 33 points and there were 75.6 % males. For the hypothermic patients, we pointed out an estimate of mean difference for the number of transfused units of packed red blood cells as well as for mortality which does not indicate a decrease in the benefit gained by hypothermia. It is suggested that hypothermic patients tend to a higher rate of lung failure and thromboembolisms.

Conclusion: Though tending to an increased rate of complications, there is no evidence for a difference in both; rate of transfusion and mortality in SIP. Mild IH as an option for severe head injuries seems as well-being practicable in the presence of multiple severe injuries. Further, clinical studies regarding the side effects are necessary.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052900PMC
http://dx.doi.org/10.1186/s40001-016-0233-xDOI Listing
October 2016

External validation of scores proposed for estimation of survival probability of patients with severe adult respiratory distress syndrome undergoing extracorporeal membrane oxygenation therapy: a retrospective study.

Crit Care 2015 Apr 7;19:142. Epub 2015 Apr 7.

Medical Intensive Care Unit, University Hospital of Zurich, Raemistrasse 100, CH-8091, Zurich, Switzerland.

Introduction: This study was designed as an external validation of the recently proposed Predicting Death for Severe ARDS on V-V ECMO (PRESERVE) score, The respiratory extracorporeal membrane oxygenation survival prediction (RESP) score and a scoring system developed for externally retrieved patients on extracorporeal membrane oxygenation (ECMO) at our institution. All scores are proposed for the estimation of survival probability after ECMO treatment for severe adult respiratory distress syndrome.

Methods: Data from 51 patients (2008 to 2013) were analyzed in this retrospective single-center study. A calculation of an adapted PRESERVE score, the RESP score as well as the score developed for externally retrieved ECMO patients was performed.

Results: Seventy one percent of patients received veno-venous (v-v) and 29% venous-arterial (v-a) ECMO support during the study period. Overall survival at 6 months was 55%, with a 61% survival rate for v-v cannulated patients and a 40% survival rate for v-a cannulated patients. The PRESERVE score discriminated survivors and non-survivors with an area under the curve of 0.67 (95% CI 0.52 to 0.82, P = 0.03). Analyzing survival prediction according to cannulation modus, the PRESERVE score and the RESP score significantly predicted survival for patients on v-v ECMO with an area under the curve of 0.75 (95% CI 0.57 to 0.92, P = 0.01) and 0.81 (95% CI 0.67 to 0.95, P = 0.035), respectively, while the scoring system developed for externally retrieved ECMO patients failed to predict survival in our study population. All scores failed to predict mortality for patients on v-a ECMO.

Conclusion: Our single-center validation confirms that the proposed PRESERVE and RESP score predict survival for patients treated with v-v ECMO for severe adult respiratory distress syndrome.
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http://dx.doi.org/10.1186/s13054-015-0875-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403939PMC
April 2015

Response to BONE-D-14-00884.

Bone 2015 Jun 4;75:246. Epub 2014 Dec 4.

Park Nicollet Institute for Research and Education, Division of Health Policy and Management, University of Minnesota, USA.

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http://dx.doi.org/10.1016/j.bone.2014.11.020DOI Listing
June 2015

Methods and reliability of radiographic vertebral fracture detection in older men: the osteoporotic fractures in men study.

Bone 2014 Oct 6;67:152-5. Epub 2014 Jul 6.

Park Nicollet Institute for Research and Education, Division of Health Policy and Management, University of Minnesota, USA.

We describe the methods and reliability of radiographic vertebral fracture assessment in MrOS, a cohort of community dwelling men aged ≥65yrs. Lateral spine radiographs were obtained at Visit 1 (2000-2) and 4.6years later (Visit 2). Using a workflow tool (SpineAnalyzer™, Optasia Medical), a physician reader completed semi-quantitative (SQ) scoring. Prior to SQ scoring, technicians performed "triage" to reduce physician reader workload, whereby clearly normal spine images were eliminated from SQ scoring with all levels assumed to be SQ=0 (no fracture, "triage negative"); spine images with any possible fracture or abnormality were passed to the physician reader as "triage positive" images. Using a quality assurance sample of images (n=20 participants; 8 with baseline only and 12 with baseline and follow-up images) read multiple times, we calculated intra-reader kappa statistics and percent agreement for SQ scores. A subset of 494 participants' images was read regardless of triage classification to calculate the specificity and sensitivity of triage. Technically adequate images were available for 5958 of 5994 participants at Visit 1, and 4399 of 4423 participants at Visit 2. Triage identified 3215 (53.9%) participants with radiographs that required further evaluation by the physician reader. For prevalent fractures at Visit 1 (SQ≥1), intra-reader kappa statistics ranged from 0.79 to 0.92; percent agreement ranged from 96.9% to 98.9%; sensitivity of the triage was 96.8% and specificity of triage was 46.3%. In conclusion, SQ scoring had excellent intra-rater reliability in our study. The triage process reduces expert reader workload without hindering the ability to identify vertebral fractures.
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http://dx.doi.org/10.1016/j.bone.2014.06.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4152008PMC
October 2014

Comprehensive vertebral deformity and vertebral fracture assessment in clinical practice: intra- and inter-reader agreement of a clinical workflow tool.

Spine (Phila Pa 1976) 2013 Dec;38(26):E1676-83

*Department of Radiology, University of Foggia, Viale Luigi Pinto, Foggia, Italy †Department of Radiology, Scientific Institute Hospital "Casa Sollievo della Sofferenza," Viale Cappuccini, San Giovanni Rotondo, Foggia, Italy ‡Optasia Medical Ltd, Mellor House, Cheadle Hulme, Cheadle, United Kingdom; and §Optasia Medical Inc, Sudbury, MA.

Study Design: Study design randomized intra- and inter-reader reproducibility study.

Objective: To evaluate reproducibility of quantitative morphometry (QM) and agreement of dichotomous fracture/no-fracture status on lateral spinal radiographs acquired during routine clinical practice using a clinical workflow tool.

Summary Of Background Data: Several recent guidelines have underlined the importance of Genant semi-quantitative scoring and selective QM to confirm and grade suspected vertebral fractures in clinical practice.

Methods: Thoracic and lumbar spine radiographs were acquired from 98 consecutive subjects (mean age, 60.1 ± 11.7 yr) attending the clinic for osteoporosis evaluation. For each subject, QM and Genant semi-quantitative scoring were performed on all evaluable vertebrae from L4 to T4 using a software workflow tool. A radiologist and an experienced radiographical technician performed 2 repeat reading sessions of the radiographs 12 months apart, blinded to each other's results; for the second read, the cases were anonymized and the order was randomized.

Results: Inter-reader reproducibility results were 3.1% and 3.2% coefficient of variation (%) for heights, 0.030 and 0.031 root mean square standard deviation for height ratios. For intrareader reproducibility, these values were 2.2% and 3.5% coefficient of variation %; 0.023 and 0.034 root mean square standard deviation. Kappa score results for agreement of dichotomous fracture/no-fracture status were 0.67 and 0.72 (inter-rater) and 0.50 and 0.67 (intrarater).

Conclusion: The software assessed in this study is a reliable clinical tool that facilitates QM and Genant semi-quantitative scoring of the spine in routine clinical practice.

Level Of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000000048DOI Listing
December 2013

The relationship between preoperative creatinine clearance and outcomes for patients undergoing liver transplantation: a retrospective observational study.

BMC Nephrol 2013 Feb 14;14:37. Epub 2013 Feb 14.

Surgical Intensive Care Medicine, University Hospital of Zurich, Raemistrasse 100, Zurich, CH 8091, Switzerland.

Background: Renal failure with following continuous renal replacement therapy is a major clinical problem in liver transplant recipients, with reported incidences of 3% to 20%. Little is known about the significance of postoperative acute renal failure or acute-on-chronic renal failure to postoperative outcome in liver transplant recipients.

Methods: In this post hoc analysis we compared the mortality rates of 135 consecutive liver transplant recipients over 6 years in our center subject to their renal baseline conditions and postoperative RRT. We classified the patients into 4 groups, according to their preoperative calculated Cockcroft formula and the incidence of postoperative renal replacement therapy. Data then were analyzed in regard to mortality rates and in addition to pre- and peritransplant risk factors.

Results: There was a significant difference in ICU mortality (p=.008), hospital mortality (p=.002) and cumulative survival (p<.0001) between the groups. The highest mortality rate occurred in the group with RRT and normal baseline kidney function (20% ICU mortality, 26.6% hospital mortality and 50% cumulative 1-year mortality, respectively). The hazard ratio in this group was 9.6 (CI 3.2-28.6, p=.0001).

Conclusion: This study shows that in liver transplant recipient's acute renal failure with postoperative RRT is associated with mortality and the mortality rate is higher than in patients with acute-on-chronic renal failure and postoperative renal replacement therapy.
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http://dx.doi.org/10.1186/1471-2369-14-37DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3582487PMC
February 2013

Use of imaging biomarkers for regulatory studies.

Authors:
Peter Steiger

J Bone Joint Surg Am 2009 Feb;91 Suppl 1:132-6

Optasia Medical Inc., 365 Boston Post Road #340, Sudbury, MA 01776, USA.

Imaging often plays an important role in pivotal clinical trials of drugs or devices that have been submitted for approval to regulatory agencies that grant approval for the marketing and sale of these products on the basis of documentation of their safety and efficacy. Imaging biomarkers can help substantiate either or both of these characteristics. This article focuses on how to successfully incorporate imaging biomarkers into clinical trials through a process of careful planning and diligent execution. Planning starts with posing and then answering a number of questions that pertain to the product under study. What will the claimed benefit of the product be? Is there a current standard of care that involves imaging, and will that standard of care help in the documentation of safety and efficacy? Are there relevant novel imaging biomarkers? Are there any relevant guidance documents issued by the regulatory agencies? After imaging biomarkers are identified, their role and benefit must be understood. Will they help diagnose subjects? Will they stratify subjects for enrollment? Will they identify those who are more likely to benefit? Will they help document progression of disease and effectiveness of intervention? Execution must occur in close collaboration with regulatory agencies and with the involvement of imaging experts and imaging core laboratories to ensure attention to key components: imaging charter, investigator training and certification, 21 CFR Part 11 (Part 11 of Title 21 of the U.S. Code of Federal Regulations)-compliant data management, real-time incoming image quality control for eligibility reads and investigator feedback, and centralized image analysis for safety and efficacy by certified readers.
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http://dx.doi.org/10.2106/JBJS.H.01545DOI Listing
February 2009

Differential temporal profile of lowered blood glucose levels (3.5 to 6.5 mmol/l versus 5 to 8 mmol/l) in patients with severe traumatic brain injury.

Crit Care 2008 4;12(4):R98. Epub 2008 Aug 4.

Surgical Intensive Care Medicine, University Hospital Zuerich, Raemistrasse 100, CH 8091 Zuerich, Switzerland.

Introduction: Hyperglycaemia is detrimental, but maintaining low blood glucose levels within tight limits is controversial in patients with severe traumatic brain injury, because decreased blood glucose levels can induce and aggravate underlying brain injury.

Methods: In 228 propensity matched patients (age, sex and injury severity) treated in our intensive care unit (ICU) from 2000 to 2004, we retrospectively evaluated the influence of different predefined blood glucose targets (3.5 to 6.5 versus 5 to 8 mmol/l) on frequency of hypoglycaemic and hyperglycaemic episodes, insulin and norepinephrine requirement, changes in intracranial pressure and cerebral perfusion pressure, mortality and length of stay on the ICU.

Results: Mortality and length of ICU stay were similar in both blood glucose target groups. Blood glucose values below and above the predefined levels were significantly increased in the 3.5 to 6.5 mmol/l group, predominantly during the first week. Insulin and norepinephrine requirements were markedly increased in this group. During the second week, the incidences of intracranial pressure exceeding 20 mmHg and infectious complications were significantly decreased in the 3.5 to 6.5 mmol/l group.

Conclusion: Maintaining blood glucose within 5 to 8 mmol/l appears to yield greater benefit during the first week. During the second week, 3.5 to 6.5 mmol/l is associated with beneficial effects in terms of reduced intracranial hypertension and decreased rate of pneumonia, bacteraemia and urinary tract infections. It remains to be determined whether patients might profit from temporally adapted blood glucose limits, inducing lower values during the second week, and whether concomitant glucose infusion to prevent hypoglycaemia is safe in patients with post-traumatic oedema.
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http://dx.doi.org/10.1186/cc6974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2575586PMC
May 2009