Christian E. Wrede

Different effects of adiponectin isoforms in human monocytic cells.

Adiponectin (APM) is an adipocyte‐derived adipokine with immunosuppressive, antidiabetic, and antiatherosclerotic properties. Low molecular weight (LMW)‐ and higher molecular weight (HMW)‐APM circulate in the serum and activate different signaling pathways. We were interested to see whether LMW‐APM exerts different effects on monocytic cells compared with the HMW isoform. Therefore, the effects of recombinant LMW‐APM produced in insect cells and the APM from higher eukaryotic cells containing HMW forms on monocytic cells were investigated with respect to apoptosis and inflammation. LMW‐ and HMW‐APM induce apoptosis in nondifferentiated THP‐1 cells, reduce macrophage scavenger receptor (MSR) A mRNA expression, and stimulate phosphorylation of adenosine monophosphate‐activated protein kinase (AMPK). However, HMW‐APM induces the secretion of interleukin (IL)‐6 in human monocytes and THP‐1 cells but does not suppress lipopolysaccharide (LPS)‐induced IL‐6 secretion. In contrast, LMW‐APM reduces LPS‐mediated IL‐6 release and furthermore, stimulates IL‐10 secretion, most likely by reducing the abundance of inhibitor of nuclear factor (NF)‐κB kinase β, leading to a diminished nuclear translocation of NF‐κB p65. Our data indicate that the different APM isoforms do share common effects on monocytic cells but also induce isoform‐specific responses. Although apoptosis, the activation of AMPK, and the reduction of MSR are mediated by all APM isoforms, only LMW‐APM displays anti‐inflammatory properties.

Intensive care unit alarms--how many do we need?

Objective: To validate cardiovascular alarms in critically ill patients in an experimental setting by generating a database of physiologic data and clinical alarm annotations, and report the current rate of alarms and their clinical validity. Currently, monitoring of physiologic parameters in critically ill patients is performed by alarm systems with high sensitivity, but low specificity. As a consequence, a multitude of alarms with potentially negative impact on the quality of care is generated. Design: Prospective, observational, clinical study. Setting: Medical intensive care unit of a university hospital. Data Source: Data from different medical intensive care unit patients were collected between January 2006 and May 2007. Measurements and Main Results: Physiologic data at 1-sec intervals, monitor alarms, and alarm settings were extracted from the surveillance network. Video recordings were annotated with respect to alarm relevance and technical validity by an experienced physician. During 982 hrs of observation, 5934 alarms were annotated, corresponding to six alarms per hour. About 40% of all alarms did not correctly describe the patient condition and were classified as technically false; 68% of those were caused by manipulation. Only 885 (15%) of all alarms were considered clinically relevant. Most of the generated alarms were threshold alarms (70%) and were related to arterial blood pressure (45%). Conclusion: This study used a new approach of off-line, video-based physician annotations, showing that even with modern monitoring systems most alarms are not clinically relevant. As the majority of alarms are simple threshold alarms, statistical methods may be suitable to help reduce the number of false-positive alarms. Our study is also intended to develop a reference database of annotated monitoring alarms for further application to alarm algorithm research.

Medical device alarms

Abstract The high number of false positive alarms has long been known to be a serious problem in critical care medicine – yet it remains unresolved. At the same time, threats to patient safety due to missing or suppressed alarms are being reported. The purpose of this paper is to present results from a workshop titled “Too many alarms? Too few alarms?” organized by the Section Patient Monitoring and the Workgroup Alarms of the German Association of Biomedical Engineering of the Association for Electrical, Electronic and Information Technologies. The current situation regarding alarms and their problems in intensive care, such as lack of clinical relevance, alarm fatigue, workload increases due to clinically irrelevant alarms, usability problems in alarm systems, problems with manuals and training, and missing alarms due to operator error are outlined, followed by a discussion of solutions and strategies to improve the current situation. Finally, the need for more research and development, focusing on signal quality considerations, networking of medical devices at the bedside, diagnostic alarms and predictive warnings, usability of alarm systems, education of healthcare providers, creation of annotated clinical databases for testing, standardization efforts, and patient monitoring in the regular ward, are called for.

Reducing False Alarms of Intensive Care Online-Monitoring Systems: An Evaluation of Two Signal Extraction Algorithms

Online-monitoring systems in intensive care are affected by a high rate of false threshold alarms. These are caused by irrelevant noise and outliers in the measured time series data. The high false alarm rates can be lowered by separating relevant signals from noise and outliers online, in such a way that signal estimations, instead of raw measurements, are compared to the alarm limits. This paper presents a clinical validation study for two recently developed online signal filters. The filters are based on robust repeated median regression in moving windows of varying width. Validation is done offline using a large annotated reference database. The performance criteria are sensitivity and the proportion of false alarms suppressed by the signal filters.

Optimized multidetector computed tomographic protocol for the diagnosis of active obscure gastrointestinal bleeding: a feasibility study.

Objective: The purpose of this feasibility study was to prospectively evaluate an optimized multidetector computed tomographic protocol for the diagnosis of active obscure gastrointestinal bleeding (OGIB). Methods: Between October 2006 and February 2008, patients admitted for active OGIB were included in this prospective unicenter study. Water was administered orally and rectally as neutral luminal contrast material. A contrast-enhanced 16-row multidetector computed tomography (MDCT) was performed in the arterial and venous phases. Mesenteric digital subtraction angiography was carried out immediately after MDCT as standard of reference. Results: Six patients were included in this study. Multidetector computed tomography identified the bleeding site and source in 5 (83%) of the patients. Digital subtraction angiography was performed in 4 patients, and the result was positive in 1 (25%) of the patients. Multidetector computed tomography detected the site and source of bleeding in 2 patients whose digital subtraction angiographic result was negative. Conclusions: The results of this feasibility study indicate that optimized MDCT is an excellent diagnostic tool for the diagnosis of active OGIB.

Severe and long lasting cholestasis after high-dose co-trimoxazole treatment for Pneumocystis pneumonia in HIV-infected patients—a report of two cases

Pneumocystis pneumonia (PCP), a common opportunistic infection in HIV-infected individuals, is generally treated with high doses of co-trimoxazole. However, treatment is often limited by adverse effects. Here, we report two cases of severely immunocompromised HIV-infected patients who developed severe intrahepatic cholestasis, and in one patient lesions mimicking liver abscess formation on radiologic exams, during co-trimoxazole treatment for PCP. Whereas patient 1 showed lesions of up to 1 cm readily detectable on magnetic resonance imaging under prolonged co-trimoxazole treatment, therapy of patient 2 was switched early.

Noise in intensive care units. Do the alarms for subspecialties differ

INTRODUCTION Cardiovascular monitoring alarms are frequent in intensive care units (ICUs) and lead to noise levels often exceeding 80 dB. The aim of this study was to evaluate if there are relevant differences between ICUs with different subspecialties in the frequency and distribution of alarm signals, their occurrence during the day, the types of alarms and the underlying vital parameters. METHODS All alarm signals of the cardiovascular monitoring systems from randomly chosen patients at five different ICUs of the university hospital of Regensburg were evaluated. RESULTS No significant differences between the ICUs regarding the frequency of alarm signals and only slight differences in the time distribution could be recognized (p=0.02). The most frequent alarm signals were from threshold alarms (61%) followed by technical alarms. The majority of alarms generated were related to invasive arterial blood pressure measurement. CONCLUSIONS The frequency and distribution of ICU alarm signals seem to be comparable on different ICUs. Therefore, implementation of universal concepts for alarm reduction seems to be applicable regardless of the subspecialty of the ICU.

Computed tomography versus digital subtraction angiography for the diagnosis of obscure gastrointestinal bleeding

PURPOSE The diagnostic yield of computed tomography angiography (CTA) compared to digital subtraction angiography (DSA) for major obscure gastrointestinal bleeding (OGIB) is not known. Aim of the study was to prospectively evaluate the diagnostic yield of CTA versus DSA for the diagnosis of major OGIB. MATERIAL AND METHODS The institutional review board approved the study and informed consent was obtained from each patient. Patients with major OGIB were prospectively enrolled to undergo both CTA and DSA. Two blinded radiologists each reviewed the CTA and DSA images retrospectively and independently. Contrast material extravasation into the gastrointestinal lumen was considered diagnostic for active bleeding. Primary end point of the study was the diagnostic yield, defined as the frequency a technique identified an active bleeding or a potential bleeding lesion. The diagnostic yield of CTA and DSA were compared by McNemars test. RESULTS 24 consecutive patients (11 men; median age 64 years) were included. CTA and DSA identified an active bleeding or a potential bleeding lesion in 92% (22 of 24 patients; 95% CI 72%-99%) and 29% (7 of 24 patients; 95% CI 12%-49%) of patients, respectively (p<0.001). CTA and DSA identified an active bleeding in 42% (10 of 24; 95% CI 22%-63%) and 21% (5 of 24; 95% CI 7%-42%) of patients, respectively (p=0.06). CONCLUSION Due to the lower invasiveness and higher diagnostic yield CTA should be favored over DSA for the diagnosis of major OGIB.

Lärm auf der Intensivstation

INTRODUCTION Cardiovascular monitoring alarms are frequent in intensive care units (ICUs) and lead to noise levels often exceeding 80 dB. The aim of this study was to evaluate if there are relevant differences between ICUs with different subspecialties in the frequency and distribution of alarm signals, their occurrence during the day, the types of alarms and the underlying vital parameters. METHODS All alarm signals of the cardiovascular monitoring systems from randomly chosen patients at five different ICUs of the university hospital of Regensburg were evaluated. RESULTS No significant differences between the ICUs regarding the frequency of alarm signals and only slight differences in the time distribution could be recognized (p=0.02). The most frequent alarm signals were from threshold alarms (61%) followed by technical alarms. The majority of alarms generated were related to invasive arterial blood pressure measurement. CONCLUSIONS The frequency and distribution of ICU alarm signals seem to be comparable on different ICUs. Therefore, implementation of universal concepts for alarm reduction seems to be applicable regardless of the subspecialty of the ICU.

Obscure Gastrointestinal Bleeding: Preoperative CT-guided Percutaneous Needle Localization of the Bleeding Small Bowel Segment

A 57-year-old woman presented with obscure gastrointestinal bleeding. Double balloon enteroscopy, angiography, and surgery including intraoperative enteroscopy failed to identify the bleeding site. Multidetector computed tomography (CT) depicted active bleeding of a small bowel segment. The bleeding segment was localized by CT-guided percutaneous needle insertion and subsequently removed surgically.