[Reasons for Emergency Department Visits: Results of a Patient Survey]. / Beweggründe für die Inanspruchnahme von Notaufnahmen ­ Ergebnisse einer Patientenbefragung.

OBJECTIVES: The number of patients visiting emergency departments (ED) is steadily increasing. The cause for this rise in Germany is unclear and less examined. This study aimed to assess the reasons of walk-in patients to visit EDs by using a direct survey. METHODS: During a period of 4 weeks, 2 010 walk-in patients were anonymously surveyed in 2 major Berlin hospitals using a standardized questionnaire. Descriptive statistics were used for data analysis. RESULTS: More than 90% of patients assessed themselves as an emergency and three-quarters of patients reported pain. The majority of patients (57%) tried to contact statutory health insurance (SHI) office-based physicians in advance and 59% of patients said they would make use of ambulatory emergency facilities if they were available and well established. However, 55% of patients were unaware of the emergency service of the association of SHI physicians. CONCLUSION: The results indicate that centralized ambulatory emergency facilities should be available 24/7 at hospitals with EDs. Therefore, future planning of emergency services should integrate providers of ambulatory and inpatient sector. International experience suggests that different instruments aiming at better coordination of care, such as integrated call centers, extended ambulatory services and facilities for less urgent cases located in or nearby hospitals with EDs should also be implemented in Germany.

[Patients with Acute, Non-Traumatic Abdominal Pain in German Emergency Departments: A Prospective Monocentric Observation Study]. / Patienten mit akutem, nicht traumatischem Abdominalschmerz in der zentralen Notaufnahme ­ eine prospektive, monozentrische Beobachtungsstudie.

Background: Up to 11 % of patients in an Emergency Department (ED) present with non-traumatic acute abdominal pain. Based on this presenting symptom, this study aimed to analyse how residents (surgery, internal medicine, anaesthesiology and other fields) working in an ED during their second and third year of education treat these patients. Material and Methods: We performed a prospective, monocentric observation study in an ED in accordance with the STROBE recommendations, following the recommendations from the Ethics Committee of the University of Ulm (application no. 335/12) and the Declaration of Helsinki. The hospital's data protection officer approved the study. During a 12-month period (Dec. 2012 to Dec. 2013), a random sample of patients with non-traumatic abdominal pain was obtained in the ED of a major German acute care hospital by an independent observer, who was not part of the ED team. In addition to demographic data, the study focused on analysing processes and patient care (including medical history taking and physical examinations). In addition, subgroups were defined (clinical background of the treating physician, severity pursuant to the Manchester Triage Score [MTS]). Results: 143 patients met the inclusion criteria. The clinical background of the physician had no influence on the reviewed processes such as medical history taking, initial examinations, the request of consultative examinations or diagnostic procedures. Patients triaged as "urgent" were treated significantly earlier than patients triaged as "non-urgent" (time to first physician contact 26 ± 24 vs. 46 ± 34 min, p < 0.001). However, the overall time spent in the ED was equal (210 ± 79 vs. 220 ± 114 min, p = 0.555). Yet the initially estimated urgency was correlated with the need for hospitalisation (share: 57 %). Conclusion: The overall compliance with standards of care was high. The clinical background (surgery, internal medicine, anaesthesiology, other fields) of the physician in charge of initial treatment had no influence on the reviewed processes.

Age-Dependent D-dimer Cut-off to Avoid Unnecessary CT-Exams for Ruling-out Pulmonary Embolism.

PURPOSE: To evaluate the effect of an age-dependent D-Dimer cut-off in patients who underwent a computed tomography pulmonary angiogram (CTPA) for suspected pulmonary embolism (PE) Material and Methods: Retrospective application of an age-dependent D-dimer cut-off (age/100 in patients aged over 50) in 530 consecutive patients, both in- and outpatients, aged over 18, who underwent CTPA for suspected PE according to the guidelines. RESULTS: The application of an age-dependent D-dimer cut-off showed a now negative test-result in 17 of 530 patients (3.2%). The proportion was 4.1% (17 of 418) in patients aged over 50. None of these 17 cases was diagnosed with PE in CTPA, the false-negative rate was 0%. The effect could be seen in outpatients (14 of 377 [3.7%]) as well as in inpatients(3 of 153 [2.0%]) with no statistically significant difference (p > 0.05). CONCLUSION: The application of an age-dependent D-dimer cut-off as part of the guidline-based algorithm for suspected PE reduced the number of necessary CTPA in outpatients as well as in inpatients. KEY POINTS: The application of an age-dependent D-dimer cut-off reduces the number of CTPA as part of the diagnostic algorithm in patients suspected for PENo reduction in diagnostic safety was found. The age adjustement performed equally in outpatients and inpatients

Multidetector computed tomography mesentericography for the diagnosis of obscure gastrointestinal bleeding.

PURPOSE: To evaluate the diagnostic yield of 16-row multidetector computed tomography (CT) mesentericography in patients with obscure gastrointestinal bleeding. MATERIALS AND METHODS: The radiological information system database was used to retrospectively identify all patients in whom CT mesentericography (CTM) was performed for the diagnosis of obscure gastrointestinal bleeding between July 2002 and September 2006. A subsequent prospective study was conducted between October 2006 and September 2009 to evaluate CTM in patients with major obscure gastrointestinal bleeding. The retrospectively identified patients (six patients) as well as the prospectively evaluated patients (seven patients) constitute the study population. Following mesenteric DSA the catheter was left in the superior mesenteric artery, the patient was transferred to the CT suite and CTM was carried out by scanning the abdomen after contrast material injection via the catheter. Active bleeding was suspected if a focal area of high attenuation consistent with contrast material extravasation was found within the bowel lumen. RESULTS: CTM detected the site of active bleeding in three of 13 patients (23 %). In the subpopulation of patients who were prospectively evaluated, CT mesentericography identified the site of active bleeding in one of seven patients (14 %). Depiction of active bleeding by CTM prompted surgical intervention in each case and surgery confirmed the findings of CT mesentericography. CONCLUSION: Due to the relatively low rate of positive findings and inherent drawbacks, we feel that CTM cannot be recommended in general. However, in selected patients who are continuously bleeding at a low rate and in whom iv-CT was negative, CT mesentericography might be helpful.

[Endocrine regulation in critically ill patients]. / Hormone in der Intensivmedizin.

Disturbances of the hormonal regulation of critically ill patients are known since many years. In the last years, two topics received a lot of attention since a single intervention led to a mortality benefit: the intensive blood glucose control in surgical intensive care patients and the low dose hydrocortisone therapy in sepsis. These results were quickly incorporated in guidelines. However, large multi-center studies failed to support the initial results in several points. This review discusses these and other disturbances of endocrine regulation of critically ill patients.

Decreased cytosolic glucocorticoid receptor levels in critically ill patients.

The immune system and the hypothalamic-pituitary-adrenal axis are linked by several mechanisms. Intracellular glucocorticoid receptors represent one important connection. The aim of this study was to examine the coherence between the number of glucocorticoid receptors, activation of the hypothalamic-pituitary-adrenal axis, inflammatory cytokine levels and the severity of illness in critically ill patients. In a prospective study, blood was collected from 20 healthy members of the hospital staff (control group) and 50 ventilated patients (sample group) within the first 24 hours after intubation and within three days of extubation. 3H-dexamethasone-binding assay was used to assess cytoplasmatic free glucocorticoid receptors levels. ACTH, cortisol, IL-6 and TNFa levels were measured by ELISA. In the sample group, specific binding of 3H-dexamethasone was significantly decreased compared to the control group. Glucocorticoid receptor levels tended to be lower in more severely ill patients. Plasma cortisol and ACTH levels were significantly different from the control group after extubation but not at intubation. Severe illness is associated with rapid down-regulation of 3H-dexamethasone binding. This decrease occurs before elevation of plasma cortisol. Therefore, down-regulation of cortisol binding may be directly associated with the stress response and not due to feedback regulation following increase in plasma cortisol levels.

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]. / Lärm auf der Intensivstation: Unterscheiden sich die Alarme in den Fachdisziplinen?

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.

Users' opinions on intensive care unit alarms--a survey of German intensive care units.

Monitoring of physiologic parameters in critically ill patients is associated with an enormous number of alarms, leading to reduced clinical value with high sensitivity but low specificity. To evaluate opinions of intensive care unit (ICU) staff on current monitoring we conducted a survey of German ICUs. Furthermore, the survey aimed to assess requirements and requests for future alarm systems. The survey was conducted between May 2006 and June 2007 on a randomised sample of German ICUs. Questionnaires with 24 partly closed-ended partly open-ended questions were posted. Of 915 letters, 274 (30%) from 185 contacted ICUs were returned and evaluated. One hundred and sixty physicians, the majority (52%) working in a department of anaesthesiology, and 114 nurses returned the survey. Most responders (87%) estimated that less than 50% of current alarms result in clinical consequences (52% estimated less than 25%). We suggested trend alarms, smoothing of signals to reduce artefacts, generation of new combined alarms and integrative monitoring of different alarm systems as improvements of current ICU alarm systems, all of which were agreed to by the majority. Free text commentaries focused on the need for reducing alarms caused by artefacts and called for improvement of the monitor-user interfaces. Our survey demonstrates the dissatisfaction of clinical staff with the current alarm systems regarding alarm frequency and specificity in German ICUs, thereby confirming data raised in single institutions. ICU staff's acceptance for new alarm algorithms like signal extraction or detection of trends as a basis for smart monitoring appealed to the majority of users.

Extracorporeal pumpless interventional lung assist in clinical practice: determinants of efficacy.

Respiratory acidosis can become a serious problem during protective ventilation of severe lung failure. A pumpless arteriovenous interventional lung assist (iLA) for extracorporeal carbon dioxide removal has been used increasingly to control critical respiratory situations. The present study sought to evaluate the factors determining the efficacy of iLA and calculate its contribution to gas exchange. In a cohort of 96 patients with severe acute respiratory distress syndrome, haemodynamic parameters, oxygen consumption and carbon dioxide production as well as gas transfer through the iLA were analysed. The measurements demonstrated a significant dependency of blood flow via the iLA device on cannula size (mean+/-sd 1.59+/-0.52 L x min(-1) for 15 French (Fr), 1.94+/-0.35 L x min(-1) for 17 Fr, and 2.22 +/-0.45 L x min(-1) for 19 Fr) and on mean arterial pressure. Oxygen transfer capacity averaged 41.7+/-20.8 mL x min(-1), carbon dioxide removal was 148.0+/-63.4 mL x min(-1). Within two hours of iLA treatment, arterial oxygen partial pressure/inspired oxygen fraction ratio increased significantly and a fast improvement in arterial carbon dioxide partial pressure and pH was observed. Interventional lung assist eliminates approximately 50% of calculated total carbon dioxide production with rapid normalisation of respiratory acidosis. Despite limited contribution to oxygen transfer it may allow a more protective ventilation in severe respiratory failure.

Outcome of patients with acute, necrotizing pancreatitis requiring drainage-does drainage size matter?

AIM: To assess the outcome of patients with acute necrotizing pancreatitis treated by percutaneous drainage with special focus on the influence of drainage size and number. METHODS: We performed a retrospective analysis of 80 patients with acute pancreatitis requiring percutaneous drainage therapy for infected necroses. Endpoints were mortality and length of hospital stay. The influence of drainage characteristics such as the median drainage size, the largest drainage size per patient and the total drainage plane per patient on patient outcome was evaluated. RESULTS: Total hospital survival was 66%. Thirty-four patients out of all 80 patients (43%) survived acute necrotizing pancreatitis with percutaneous drainage therapy only. Eighteen patients out of all 80 patients needed additional percutaneous necrosectomy (23%). Ten out of these patients required surgical necrosectomy in addition, 6 patients received open necrosectomy without prior percutaneous necrosectomy. Elective surgery was performed in 3 patients receiving cholecystectomy and one patient receiving resection of the parathyroid gland. The number of drainages ranged from one to fourteen per patient. The drainage diameter ranged from 8 French catheters to 24 French catheters. The median drainage size as well as the largest drainage size used per patient and the total drainage area used per patient did not show statistically significant influence on mortality. CONCLUSION: Percutaneous drainage therapy is an effective tool for treatment of necrotizing pancreatitis. Large bore drainages did not prove to be more effective in controlling the septic focus.

Systematic analysis of the insulinotropic and glucagonotropic potency of saturated and monounsaturated fatty acid mixtures in rat pancreatic islets.

BACKGROUND: Blood contains a mixture of different fatty acids (FFAs) with palmitate and oleate as major components whose molar ratio is dependent on dietary habits. Based on the theory of lipotoxicity for the development of type 2 diabetes such variances in the FFA composition might interfere with lipotoxic effects on the endocrine pancreas. METHODS: Using different ratios of FFA mixtures with palmitate and oleate, we have looked at FFA specific effects on the secretion of mature insulin and glucagon in isolated rat pancreatic islets. RESULTS: The insulinotropic potency of the oleate dominated FFA solutions was stronger than that of the palmitate dominated FFA mixtures. Conversely, the glucagonotropic potency was stronger in the palmitate dominated FFA mixtures. Palmitate and oleate similarly contributed to an impaired release of mature insulin at 16.7 mM of glucose. CONCLUSION: Based on the present IN VITRO data, FFA specific differences in terms of glucagonotropic and insulinotropic potency appear rather slight. For the IN VIVO situation, it may be assumed that the dietary influence of saturated and monounsaturated fatty acids on hyperproinsulinemia or hyperglucagonemia are rather secondary for the development of type 2 diabetes.

[Intensive care support of patients after stem cell transplantation]. / Intensivmedizinische Betreuung von Patienten nach Stammzelltransplantation.

Within the hematologic therapy procedures, stem cell transplantation (SCT) represents the most extensive and invasive intervention. Those patients have certain risks for several bacterial, viral, as well as fungal infections during the different stages of transplantation. Especially in allogenic transplantation, discrimination of non-infectious, mostly immunologic complications like graft-versus-host reactions or VOD (veno-occlusive disease) is crucial, and often represents a therapeutic challenge. An adequate intensive care therapy of these patients can only be achieved with the knowledge of the specific complications of SCT. This review starts with an overview of the SCT stages with their corresponding infectious and noninfectious complications, followed by the discussion of organ specific pulmonary, renal, cardiac, gastrointestinal, hepatic and neurological complications of stem cell transplantation.

Defining high-fat-diet rat models: metabolic and molecular effects of different fat types.

High-fat (HF)-diet rodent models have contributed significantly to the analysis of the pathophysiology of the insulin resistance syndrome, but their phenotype varies distinctly between different studies. Here, we have systematically compared the metabolic and molecular effects of different HF with varying fatty acid compositions. Male Wistar rats were fed HF diets (42% energy; fat sources: HF-L - lard; HF-O - olive oil; HF-C - coconut fat; HF-F - fish oil). Weight, food intake, whole-body insulin tolerance and plasma parameters of glucose and lipid metabolism were measured during a 12-week diet course. Liver histologies and hepatic gene expression profiles, using Affymetrix GeneChips, were obtained. HF-L and HF-O fed rats showed the most pronounced obesity and insulin resistance; insulin sensitivity in HF-C and HF-F was close to normal. Plasma omega-3 polyunsaturated fatty acid (omega-3-PUFA) and saturated fatty acid (C(12)-C(14), SFA) levels were elevated in HF-F and HF-C animals respectively. The liver histologies showed hepatic steatosis in HF-L, HF-O and HF-C without major inflammation. Hepatic SREBP1c-dependent genes were upregulated in these diets, whereas PPARalpha-dependent genes were predominantly upregulated in HF-F fed rats. We detected classical HF effects only in diets based on lard and olive oil (mainly long-chain, saturated (LC-SFA) and monounsaturated fatty acids (MUFA)). PUFA- or MC-SFA-rich diets did not induce insulin resistance. Diets based on LC-SFA and MUFA induced hepatic steatosis with SREBP1c activation. This points to an intact transcriptional hepatic insulin effect despite resistance to insulin's metabolic actions.

Association between serum ferritin and the insulin resistance syndrome in a representative population.

OBJECTIVE: Unexplained hepatic iron overload with increased serum ferritin (SF) values has been associated with the insulin resistance syndrome (IRS), defined by the presence of one or more of the following criteria: increased body mass index (BMI), diabetes, hyperlipidemia or hypertension. However, as yet the association between IRS and SF in a representative population has not been investigated. METHODS: The study subjects participated in a nationwide epidemiological survey on metabolic disorders in the adult German population. The 1200 probands included in this study are representative of the German population. To eliminate major causes of secondary iron overload, 114 (9.5%) subjects with excessive alcohol consumption and 16 (1.5%) subjects with serological evidence for hepatitis B or C were excluded. For all remaining 1070 probands, complete clinical data of SF, HbA1c, known diabetes, BMI, cholesterol, high-density lipoprotein-cholesterol and blood pressure were available. RESULTS: SF values were significantly increased in men and women with high BMI (> 25 kg/m2), increased cholesterol (> 200 mg/dl), and increased systolic (> 160 mmHg) blood pressure, in women with diabetes, and in men with increased diastolic (> 95 mmHg) blood pressure. Furthermore, there was a significant correlation between the number of IRS criteria and SF. CONCLUSIONS: This study shows a significant correlation between SF and the presence of IRS criteria in a large representative population. Interestingly, the severity of the IRS seems to be associated with increased SF levels suggesting a causal connection. Further studies are required to investigate the pathophysiological mechanism and consequences of increased SF levels in patients with IRS.

Insulin-sparing effects of troglitazone in rat pancreatic islets.

Thiazolidinediones (TZDs) have been suggested to act beneficially on pancreatic islet function and on beta-cell viability but data concerning direct effects on isolated islets are controversial. Therefore, we have examined parameters of pancreatic insulin and glucagon secretion and biosynthesis in TZD-exposed rat pancreatic islets under physiological glucose level conditions and under conditions of glucolipotoxicity. Primary rat islets were incubated for 2.5 h with or without troglitazone (10 microM) in 5.6 mM glucose (standard glucose levels) and 16.7 mM glucose (high glucose levels); a subgroup was additionally treated with oleate (200 microM) to simulate acute glucolipotoxicity. Insulin and glucagon secretion, intracellular content and their respective mRNAs were quantified. Newly synthesized insulin was determined by pulse-labeling experiments. Troglitazone reduced insulin secretion at standard and high glucose levels by about one-third (P

Fatty acid and phorbol ester-mediated interference of mitogenic signaling via novel protein kinase C isoforms in pancreatic beta-cells (INS-1).

It is possible that activation of protein kinase C (PKC) isoforms by free fatty acids (FFA) plays a role in the failure of pancreatic beta-cell mass expansion to compensate for peripheral insulin resistance in the pathogenesis of type-2 diabetes. The effect of lipid moieties on activation of conventional (PKC-alpha and -beta1), novel (PKC-delta) and atypical (PKC-zeta) PKC isoforms was evaluated in an in vitro assay, using biotinylated neurogranin as a substrate. Oleoyl-Coenzyme A (CoA) and palmitoyl-CoA, but not unesterified FFA, significantly increased the activity of all PKC isoforms (P< or =0.05), particularly that for PKC-delta. It was found that FFA (0.4 mM oleate/complexed to 0.5% bovine serum albumin) inhibited IGF-I-induced activation of protein kinase B (PKB) in the pancreatic beta-cell line (INS-1), but this was alleviated in the presence of the general PKC inhibitor (Gö6850; 1 microM). To further investigate whether conventional or novel PKC isoforms adversely affect beta-cell proliferation, the effect of phorbol ester (phorbol 12-myristate 13-acetate; PMA)-mediated activation of these PKC isoforms on glucose/IGF-I-induced INS-1 cell mitogenesis, and insulin receptor substrate (IRS)-mediated signal transduction was investigated. PMA-mediated activation of PKC (100 nM; 4 h) reduced glucose/IGF-I mediated beta-cell mitogenesis (>50%; P< or =0.05), which was reversible by the general PKC inhibitor Gö6850 (1 microM), indicating an effect of PKC and not due to a non-specific PMA toxicity. PMA inhibited IGF-I-induced activation of PKB, correlating with inhibition of IGF-I-induced association of IRS-2 with the p85 regulatory subunit of phosphatidylinositol-3 kinase. However, in contrast, PMA activated the mitogen-activated protein kinases, Erk1/2. Titration inhibition analysis using PKC isoform inhibitors indicated that these PMA-induced effects were via novel PKC isoforms. Thus, FFA/PMA-induced activation of novel PKC isoforms can inhibit glucose/IGF-I-mediated beta-cell mitogenesis, in part by decreasing PKB activation, despite an upregulation of Erk1/2. Thus, activation of novel PKC isoforms by long-chain acyl-CoA may well contribute to decreasing beta-cell mass in the pathogenesis of type-2 diabetes, similar to their inhibition of insulin signal transduction which causes insulin resistance.

Free fatty acid-induced inhibition of glucose and insulin-like growth factor I-induced deoxyribonucleic acid synthesis in the pancreatic beta-cell line INS-1.

Pancreatic beta-cell mitogenesis is increased by insulin-like growth factor I (IGF-I) in a glucose-dependent manner. In this study it was found that alternative beta-cell nutrient fuels to glucose, pyruvate, and glutamine/leucine independently induced and provided a platform for IGF-I to induce INS-1 cell DNA synthesis in the absence of serum. In contrast, long chain FFA (>/=C(12)) inhibited 15 mM glucose-induced [(3)H]thymidine incorporation (+/-10 nM IGF-I) by 95% or more within 24 h above 0.2 mM FFA complexed to 1% BSA (K(0.5) for palmitate/1% BSA = 65-85 microM for 24 h; t(0.5) for 0.2 mM palmitate/1% BSA = approximately 6 h). FFA-mediated inhibition of glucose/IGF-I-induced ss-cell DNA synthesis was reversible, and FFA oxidation did not appear to be required, nor did FFA interfere with glucose metabolism in INS-1 cells. An examination of mitogenic signal transduction pathways in INS-1 cells revealed that glucose/IGF-I induction of early signaling elements in SH2-containing protein (Shc)- and insulin receptor substrate-1/2-mediated pathways leading to downstream mitogen-activated protein kinase and phosphoinositol 3'-kinase activation, were unaffected by FFA. However, glucose-/IGF-I-induced activation of protein kinase B (PKB) was significantly inhibited, and protein kinase Czeta was chronically activated by FFA. It is possible that FFA-mediated inhibition of ss-cell mitogenesis contributes to the reduction of beta-cell mass and the subsequent failure to compensate for peripheral insulin resistance in vivo that is key to the pathogenesis of obesity-linked diabetes.