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Biomedical subjects

Edmund A M Neugebauer

Publications and source records attributed to Edmund A M Neugebauer.

16 recordsLinked to original sources

Guidelines for emergency laparoscopy.

Acute abdominal pain is a leading symptom in many surgical emergency patients. Laparoscopy allows for accurate diagnosis and immediate therapy of many intraabdominal pathologies. The guidelines of the EAES (European Association for Endoscopic Surgery) provides scientifically founded recommendations about the role of laparoscopy in the different situations. Generally, laparoscopy is well suited for the therapy of the majority of diseases that cause acute abdominal pain.

Editorial↗

Applying evidence-based surgery in daily clinical routine: a feasibility study.

BACKGROUND: Although the word evidence-based medicine (EBM) has gained wide popularity, only a few studies have evaluated how EBM works in clinical practice. METHODS: We have prospectively evaluated the feasibility of evidence-based trauma surgery. Orthopaedic trauma surgeons were asked to produce clinical questions related to the treatment of current patients. An informaticist searched the literature (Medline, Cochrane Library, practice guidelines and textbooks) and reported the findings on every following day. The study's main endpoints were the rate of questions for which relevant evidence (>level V) was available and the time necessary to find and critically appraise medical evidence. RESULTS: In total, 44 EBM questions were formulated, mainly concerning treatment options. PubMed was searched for 39 questions, textbooks for 14, the Cochrane Library for 11, online guidelines for 9 and other sources were used for 4 questions. On average, 157 text items (three per questions) were identified as potentially relevant. Journal articles predominated (83%) over textbooks (10%). Sixty-eight percent of the questions (30 of 44) were answered, either on the basis level 1 (n=13 questions), level 2 (n=6), or level 4 evidence (n=14). Trying to answer a question required 53 min on average, split up between 39 min of database searches and 25 min of obtaining full text articles. In four cases, the evidence suggested a change in clinical management. The physicians were very appreciative of our project and found the provided evidence very helpful for their clinical decisions. CONCLUSIONS: Time will be the main barrier against the introduction of clinical EBM. It is likely that clinicians reduce EBM to those situations where evidence is likely to be found. Although the impact of EBM on patient-care was limited, the concept of EBM was successfully implemented.

Adult↗

Trauma Associated Severe Hemorrhage (TASH)-Score: probability of mass transfusion as surrogate for life threatening hemorrhage after multiple trauma.

BACKGROUND: To develop a simple scoring system that allows an early and reliable estimation for the probability of mass transfusion (MT) as a surrogate for life threatening hemorrhage following multiple trauma. METHODS: Potential clinical and laboratory variables documented in the Trauma Registry of the German Trauma Society (DGU) (1993-2003; n=17,200) were subjected to univariate and multivariate logistic regression analysis to predict the probability for MT. RESULTS: Clinical and laboratory variables available from data sets were screened for their association with mass transfusion. MT was defined by transfusion requirement of >or=10 units of packed red blood cells from emergency room (ER) to intensive care unit admission. Seven independent variables were identified to be significantly correlated with an increased probability for MT: systolic blood pressure (<100 mm Hg=4 pts, <120 mm Hg=1 pt), hemoglobin (<7 g/dL=8 pts, <9 g/dL=6 pts, <10 g/dL=4 pts, <11 g/dL=3 pts, and <12 g/dL=2 pts), intra-abdominal fluid (3 pts), complex long bone and/or pelvic fractures (AIS 3/4=3 pts and AIS 5=6 pts), heart rate (>120=2 pts), base excess (<-10 mmol/L=4 pts, <-6 mmol/L=3 pts, and <-2 mmol/L=1 pt), and gender (male=1 pt). These variables were incorporated into a risk score, the Trauma Associated Severe Hemorrhage Score (TASH-Score, 0-28 points). Performance of the score was tested with respect to discrimination, precision, and calibration. Increasing TASH-Score points were associated with an increasing probability for MT. CONCLUSION: The TASH-Score is an easy-to-use scoring system that reliably predicts the probability for MT after multiple trauma. Taken as a surrogate for life threatening bleeding calculation may focus attention on relevant variables indicative for risk and impact strategies to stop bleeding and stabilize coagulation in acute trauma care.

Adult↗

Reversal of neuromotor and cognitive dysfunction in an enriched environment combined with multimodal early onset stimulation after traumatic brain injury in rats.

This study was designed to investigate the additional benefits of a multimodal early onset stimulation (MEOS) paradigm when combined with enriched environment (EE) versus EE only and standard housing (SH) on the recovery after experimental traumatic brain injury (TBI). Male Sprague- Dawley rats were subjected to moderate lateral fluid percussion (LFP) brain injury (n = 40) or sham operation (n = 6). Thereafter, the injured and sham/EE + MEOS and EE only groups were placed into a complex EE consisting of tunnel-connected wide-bodied cages with various beddings, inclining platforms, and toys. Along with group living and environmental complexity, injured and sham/EE + MEOS animals were additionally exposed to a standardized paradigm of multimodal stimulation including auditory, visual, olfactory, and motor stimuli. In contrast, injured and sham/SH groups were housed individually without stimulation. A standardized composite neuroscore (NS) test was used to assess acute post-traumatic neuromotor deficits (24 h after injury) and recovery on days 7 and 15; recovery of cognitive function was assessed on days 11-15 using the Barnes maze. Neuromotor impairment was comparable in all injured animals at 24 h post-injury, but braininjured EE + MEOS rats performed significantly better than both brain-injured SH and EE groups when tested on post-injury days 7 and 15 (p = 0.004). Similarly, latencies to locate the hidden box under the Barnes maze platform were significantly shortened in EE + MEOS animals at day 15 (p = 0.003). These results indicate that the reversal of neuromotor and cognitive dysfunction after TBI can be substantially enhanced when MEOS is added to EE.

Acoustic Stimulation↗

Characterization of a new rat model of experimental combined neurotrauma.

Traumatic brain injury (TBI) is present in two-thirds of patients with multiple injuries and in one-third combined with injuries of the extremities. Studies on interactive effects between central and peripheral injuries are scarce due to the absence of clinically relevant models. To meet the demand for "more-hit" models, an experimental model of combined neurotrauma (CNT) incorporating a standardized TBI via lateral fluid percussion (LFP) together with a peripheral bone fracture, i.e., tibia fracture, is introduced. Sprague-Dawley rats were randomized to four experimental groups: controls (n = 10), animals with TBI (n = 30), animals with tibia fracture (n = 30), and animals with CNT (n = 30). Morphological aspects of brain and bone injury were analyzed via standard histopathological procedures and x-ray. Trauma-induced neuromotor dysfunction was assessed using a standardized neuroscore. For interactive effects between injuries, we studied the extent and temporal pattern of circulating interleukin 6 (IL-6) levels via immunoassay and callus formation at fracture sites by means of microradiography. LFP produced an ipsilateral lesion with cortical contusion, hemorrhage, mass shift, and neuronal cell loss (adjacent cortex and hippocampus CA-2/-3), along with contralateral neuromotor dysfunction. X-rays confirmed complete fractures in the middle of the bone shaft. The type of injury (P < 0.001) and time (P = 0.022) were significantly associated with increased IL-6 levels. CNT produced the highest IL-6 plasma levels with a maximum peak at 6 h after trauma (P < 0.001). Similarly, callus formation at fracture sites in CNT was significantly increased versus fracture only (P < 0,01). The CNT model mimics a variety of clinically relevant features known from human multiple injury, including TBI, and offers novel approaches for investigation of interactive mechanisms and therapeutic approaches.

Animals↗

Evaluation of criteria for temporary external fixation in risk-adapted damage control orthopedic surgery of femur shaft fractures in multiple trauma patients: "evidence-based medicine" versus "reality" in the trauma registry of the German Trauma Society.

BACKGROUND: Femur-shaft fracture treatment (FSFT) follows controversial management concepts after multiple trauma: primary-definitive osteosynthesis, secondary-definitive osteosynthesis after temporary external fixation (EF) in all patients, or individualized primary- or secondary-definitive osteosynthesis ("risk-adapted damage control orthopedics"). This study compares the concepts by analyzing literature evidence and a prospective multicenter database. METHODS: A systematic literature analysis was performed. The German Trauma Society trauma registry was used to assess variables predictive of treatment concept. RESULTS: Contradictory results in 63 controlled trials failed to support a "generalized management strategy." In all, 1,465 FSFTs in 8,057 trauma registry patients (age 39 +/- 19.5 years; Injury Severity Score [ISS] 23.5 +/- 14.9; 17.3% mortality) were treated initially (<24 hour) by EF, nail, or plate in 47.0%, 41.1%, and 11.9%, respectively. Despite large interhospital variability, EF was more likely with increasing severity of ISS, Glasgow Coma Score, thorax trauma, base excess, coagulation abnormalities, and initial probability of death. CONCLUSIONS: Clinical "reality" reflects the controversies of "scientific evidence" for FSFT after multiple trauma in Germany. Although decision making is currently based on unvalidated criteria, anatomic and physiologic injury severity appears to influence the choice of management concept.

Adolescent↗

Reduced colonization and infection with miconazole-rifampicin modified central venous catheters: a randomized controlled clinical trial.

OBJECTIVE: Central venous catheters (CVC) are a major cause of nosocomial bloodstream infections. Catheters modified with miconazole and rifampicin that constantly and slowly release antimicrobial substances are assumed to be beneficial in reducing rates of colonization and catheter-related infections. DESIGN AND SETTING: Prospective controlled non-blinded randomized clinical trial in two German university hospitals. PATIENTS: 223 adult inpatients with CVC between October 2000 and February 2002. Baseline characteristics, APACHE II score and therapeutic interventions were comparable. INTERVENTION: Randomization to receive either a miconazole and rifampicin modified catheter (n=118) or a standard triple-lumen CVC (n=105). MEASUREMENTS, DEFINITIONS: Microbiological evaluation was done after CVC removal. A catheter was considered colonized if growth of > or =15 cfu was found by semi-quantitative roll-plate technique from a proximal or distal catheter segment. A catheter-related infection (CRI) was defined as a colonized catheter with local signs of inflammation. A catheter-related bloodstream infection (CR-BSI) was defined as a colonized catheter with isolation of the same organism from the patient's blood with accompanying clinical signs of infection. RESULTS: A colonization of CVC was observed in six patients (5.1%) with a modified catheter and 38 patients (36.2%) with a standard catheter (P < 0.001). Five patients in the modified group (4.2%) and 18 in the standard group (17.1%) developed CRI (P=0.002). One assumed CR-BSI was detected in the standard group, with none in the modified group. No adverse effects related to the modified catheters and no antimicrobial resistance were observed. CONCLUSION: CVC supersaturated with miconazole and rifampicin were associated with a significantly lower risk for catheter colonization and catheter-related infections compared to standard catheters.

Adolescent↗

The reliability of clinical examination in detecting pelvic fractures in blunt trauma patients: a meta-analysis.

INTRODUCTION: Several studies have recently questioned whether routine radiographic screening for pelvic fractures is necessary in the initial evaluation of blunt trauma patients. Therefore, we assessed how sensitive and specific the clinical examination is in detecting fractures of the pelvis. METHODS: We extensively searched various medical databases for studies that reported on the accuracy of pelvic examination in severely injured adults or children. Individual study results were summarized in a receiver operating characteristics (ROC) curve and pooled in a meta-analysis. RESULTS: Twelve studies with a total of 5454 patients met our inclusion criteria and provided data in sufficient detail. Pooled sensitivity and specificity were 0.90 (95% confidence interval: 0.85-0.93) and 0.90 (0.84-0.94), respectively. Results were better in those studies which excluded neurologically impaired patients [e.g., Glasgow Coma Scale (GCS) <13]. Among the 49 false negative cases whose fractures went undetected on clinical examination, the majority of patients had either altered consciousness or minor pelvic fracture only. Only 3 clinically relevant pelvic fractures were missed among 441 patients with fracture within a total population of 5235 patients. CONCLUSION: In stable and alert trauma patients, a thorough clinical examination will detect pelvic fractures with nearly 100% sensitivity, thus rendering initial radiography unnecessary in this group of patients.

False Negative Reactions↗

Plasma levels of procalcitonin and neopterin in multiple trauma patients with or without brain injury.

Clinical and experimental evidence suggests that traumatic brain injury (TBI) leads to a systemic immune response. To examine whether TBI causes a release of procalcitonin (PCT) or neopterin (NT) into the circulation, we compared plasmatic mediator levels among multiple injured patients with or without TBI. In total, 98 trauma patients (24 with TBI only, 39 with extracranial injuries excluding TBI, and 35 with combined injuries) and 35 healthy volunteers were studied. Blood was sampled at 15 predefined time points within 132 h after injury and analysed for NT and PCT. Multivariate statistical comparisons were adjusted for different severity of head, thorax, abdomen and extremity injuries, as quantified by the Abbreviated Injury Scale (AIS). PCT was normal 3 h after trauma, but 24 h after extracranial injuries a massive release (median 3 ng/mL) was observed. Significant positive associations between injury severity and posttraumatic PCT levels were found for abdominal and extremity, but not for cranial or thoracic injuries. Only modest changes of marginal statistical significance were detected for NT. The maximum increase per AIS point was 9% (95% confidence intervals [CI]: 3-16%). The effect of TBI on NT release was significant only at 108 h posttrauma with a 5% (95% CI: 1-10%) increase per AIS point. TBI induces a release of PCT and NT into the plasma, but this effect seems to be smaller for intra- than for extracranial injuries, probably due to more extensive surgery for abdominal and extremity injuries.

Adult↗

The clinical value of procalcitonin and neopterin in predicting sepsis and organ failure after major trauma.

We examined whether procalcitonin (PCT) or neopterin (NT) are useful in predicting sepsis, multiple organ failure (MOF), or death after multiple trauma (MT). In a prospective clinical study, a total of 137 consecutive trauma patients (mean age 39 years, median injury severity score [ISS] 27 points) and 34 healthy volunteers were enrolled. Blood samples were collected on arrival in the emergency room until day 28 after trauma. Plasma NT was detected by enzyme-linked immunoassay and PCT plasma levels were determined using an immunoluminometric assay. The incidence of sepsis was 65%, MOF 48%, and death in hospital within 28 days 11%. After adjustment for age, gender, and ISS, PCT and NT levels during the first 2 days after injury were unable to differentiate between patients who developed sepsis or not. On the contrary, patients who developed MOF had higher PCT plasma levels on day 0 (0.60 vs. 0.15 ng/mL), and on days 1 and 2 combined (1.95 vs. 0.32 ng/mL). This difference remained significant in multivariate logistic regression (P = 0.01) and additional subgroup analyses for early and late MOF (P = 0.048 and 0.002). For NT, smaller differences were observed (4.39 vs. 3.68 nmol/L, and 7.20 vs. 5.79 nmol/L), which lost significance in multivariate analysis. On the basis of PCT, ISS, and age, a MOF prediction rule was developed and had a good predictive power (area under the curve: 0.77; P < 0.001). These findings demonstrate that high plasma concentrations of PCT in the early posttraumatic phase are an independent predictor of MOF but not of sepsis.

Abbreviated Injury Scale↗

Immunologic alterations associated with high blood transfusion volume after multiple injury: effects on plasmatic cytokine and cytokine receptor concentrations.

The initial transfusion therapy after trauma has been identified as an independent risk factor for the incidence of multiple organ failure (MOF). Late occurrence of MOF in severely injured patients may be a clinical consequence of disturbed mediator homeostasis. For this reason, levels of interleukin (IL)-6, IL-10, and soluble tumor necrosis factor receptors (sTNFR) p55 and p75 were analyzed in the plasma of patients with comparable injury severity but with a different supply of packed red blood cells (PRBC). Thirty-eight multiple trauma patients with an injury severity score range of 25-54 points were separated into two groups according to their PRBC supply within the first 24 h after trauma. Patients who received at least 15 units of PRBC were analyzed in group 2 (n = 11); the remaining patients (n = 27) were assigned to group 1. The incidence of MOF was higher (P < 0.05) in group 2 patients. Correspondingly, levels of all assayed mediators were found significantly elevated at several time points in this patient group. We conclude that increases in mediator concentrations may be causally related to the extent of blood transfusion therapy itself or to the conditions for which it was needed.

Adult↗

An experiment of mailing physician surveys on two different issues in joint or separate mail.

High response rates from physicians play an important role in obtaining valid data on practice patterns. We wanted to know whether two questionnaires (one on hernia surgery and one on perioperative pain management) should better be sent out in one letter or two separate letters. We randomized 2,393 surgeons who received the two questionnaires either in one letter or by separate mail, in two letters, at a time interval of 4 weeks. The response rate for the separate mailout was not significantly higher when compared to the joint mailout. The differences were 3.3% (95%-CI -0,4% to 7.1%) and 2.2% (95%-CI -1,4% to 5.9%) for the two surveys. Due mainly to higher postage costs, the costs per response were doubled in the separate mailout group (5.85 Euro versus 2.93 Euro). Sending out two surveys separately seems to have only little effect on the response rates.

Data Collection↗

Expression of the thrombin receptor PAR-1 correlates with tumour cell differentiation of pancreatic adenocarcinoma in vitro.

Patients with pancreatic cancer frequently suffer from thrombosis due to excess thrombin generation. Yet, the effects of thrombin on pancreatic cancer are still poorly understood. The thrombin receptor PAR-1 is responsible for cellular effects of thrombin. PAR-1 plays an important role in the progression of different solid tumours in vitro. In breast cancer the level of PAR-1 expression correlates with invasiveness. Our aim was to correlate PAR-1 mRNA and protein expression level with the grade of differentiation of pancreatic tissue and cancer cell lines. PAR-1 protein was not detectable in the epithelium of healthy pancreas. Analysis of PAR-1 protein expression by immunofluorescence staining of pancreatic cancer cell lines revealed a correlation to the grade of differentiation. Quantitative analysis of PAR-1 protein expression by Western Blot analysis confirmed these observations. Analysis of PAR-1 mRNA expression showed low levels in healthy pancreas compared to pancreatic cancer tissue and the pancreatic cancer cell line MIA PaCa-2. The level of PAR-1 mRNA differed up to 25 fold between the respective pancreatic cancer cell lines. The eminent differences in PAR-1 expression, both protein and mRNA, between healthy pancreatic tissue and pancreatic cancer in vivo and in vitro emphasise the putative role of PAR-1 in pancreatic cancer progression.

Adenocarcinoma↗

Association between injury pattern of patients with multiple injuries and circulating levels of soluble tumor necrosis factor receptors, interleukin-6 and interleukin-10, and polymorphonuclear neutrophil elastase.

BACKGROUND: Our knowledge about the bidirectional interactions between brain and whole organism after trauma is still limited. It was the purpose of this prospective clinical study to determine the influence of severe head trauma (SHT) as well as trauma in different anatomic injury regions on posttraumatic inflammatory mediator levels from patients with multiple injuries. METHODS: Thirty-five healthy controls, 33 patients with an isolated SHT, 47 patients with multiple injuries without SHT, and 45 patients with both SHT and multiple injuries were studied. The posttraumatic plasma levels of soluble tumor necrosis factor receptors p55 and p75, interleukin (IL)-6, IL-10, and polymorphonuclear neutrophil (PMN) elastase were monitored using enzyme-linked immunosorbent assay technique. The influence of head injuries as well as thorax, abdomen, and extremity injuries on the mediator release from patients with multiple injuries was investigated by multivariate linear regression models. RESULTS: The soluble tumor necrosis factor receptor p55/p75 ratio was significantly elevated within 3 hours of trauma in all three injury groups and returned to reference ratios after 12 hours. The lowest increase was found in patients suffering from an isolated SHT. Lowest mediator levels in this patient population were also found for IL-6, IL-10, and PMN elastase during the first 36 hours after trauma. Additional injuries to the head, thorax, abdomen, and extremity modulated mediator levels to a different degree. No specific effect was found for SHT when compared with other injury groups. Thorax injuries caused the quickest rise in mediator levels, whereas abdominal injuries significantly increased PMN elastase levels 12 to 24 hours after trauma. CONCLUSION: Traumatic injuries cause the liberation of various mediators, without any specific association between anatomic injury pattern and the pattern of mediator release.

Adult↗

Local lactate and histamine changes in small bowel circulation measured by microdialysis in pig hemorrhagic shock.

Hemorrhagic shock results in inadequate tissue oxygenation. Plasma lactate (L) can characterize the degree of systemic oxygen debt (OD), but gives no information on local changes. The aim of this study was to characterize different degrees of hemorrhagic shock by microdialysis measurement of L and histamine (H) in small bowel circulation. Thirty-eight pigs were randomized to five groups of increasing OD (< 50 --> 120 ml/kg). The OD was accrued by hemorrhage over 60 min and was followed by retransfusion and observation for 3 days. In parallel to plasma probes, subserosa(ss)-, submucosa(sm)-, and intraluminal(il)-L- and H-probes were obtained by small bowel microdialysis every 30 min for 210 min. Ss- and sm-L increased during hemorrhage from 1.2 +/- 0.06 and 1.18 +/- 0.06 to 2.57 +/- 0.15 and 2.96 +/- 0.27 mmol/L. Highest mean L > 3.5mmol/L resulted 90 and 120 min after induction of hemorrhage. Although ss- and sm- levels hardly differed, il-L was significantly decreased with 0.27 +/- 0.02 mmol/L at 0 min and highest mean il-L at 120 min: 2.45 +/- 0.51 mmol/L. Sm-L was significantly increased after 60, 90, 120, and 150 min of highest hemorrhage severity (OD > 100 mL/kg). In parallel, systemic L increased significantly during hemorrhage and correlated well with the severity of shock. Although systemic H increased significantly during hemorrhage (from 1.3 +/- 0.31 to 15.2 +/- 0.67 ng/mL), H-dialysates showed no effect either over time nor with the degree of hemorrhage. In conclusion, microdialysis allows evaluation of local L changes in small bowel circulation in pig hemorrhagic shock. Sm-L levels appear to correlate with the degree of shock. Local H changes were not observed during hemorrhagic shock in this study.

Animals↗

Laparoscopic versus open appendectomy: between evidence and common sense.

BACKGROUND: Laparoscopic surgery has been proposed to have diagnostic and therapeutic advantages over conventional surgery. The purpose of this article is to present a recently completed Cochrane review on laparoscopic surgery for suspected appendicitis on the background of daily surgical practice and the developments in the last decade. METHODS: Within the Cochrane review, various medical databases (Medline, Embase, Cochrane, SciSearch) were searched electronically until October 2001. Congress proceedings were searched by hand. Randomized controlled trials were included that assessed the therapeutic effects of laparoscopic appendectomy (LA) versus open appendectomy (OA) in adults and children, the diagnostic effects of laparoscopy followed by LA or OA if necessary versus immediate OA, and the therapeutic effects of diagnostic laparoscopy followed by OA if necessary versus immediate OA. RESULTS: Based on 45 studies, wound infection was half as likely while intra-abdominal abscesses were three times more frequent after LA. Return to normal activity showed a uniform tendency in favor of LA. Pain was also reduced, but data vary and most primary studies were not blinded. Obvious diagnostic advantages concerned the negative appendectomy rate and the rate of patients without established diagnosis, both being reduced to 0.2-0.3 (RR). CONCLUSION: The review finds that laparoscopic surgery for suspected appendicitis has diagnostic and therapeutic advantages as compared to conventional surgery--a fact which is in full agreement with the daily practice of surgeons interested in endoscopic surgery.

Abdominal Abscess↗