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Background: Sepsis and complications to sepsis are major causes of mortality in critically ill patients. Rapid treatment of sepsis is of crucial importance for survival of patients. The infectious status of the critically ill patient is often difficult to assess because symptoms cannot be expressed and signs may present atypically. The established biological markers of inflammation (leucocytes, C-reactive protein) may often be influenced by other parameters than infection, and may be unacceptably slowly released after progression of an infection. At the same time, lack of a relevant antimicrobial therapy in an early course of infection may be fatal for the patient. Specific and rapid markers of bacterial infection have been sought for use in these patients.Methods: Multi-centre randomized controlled interventional trial. Powered for superiority and non-inferiority on all measured end points. Complies with, "Good Clinical Practice" (ICH-GCP Guideline (CPMP/ICH/135/95, Directive 2001/20/EC)). Inclusion: 1) Age > or = 18 years of age, 2) Admitted to the participating intensive care units, 3) Signed written informed consent.Exclusion: 1) Known hyper-bilirubinaemia. or hypertriglyceridaemia, 2) Likely that safety is compromised by blood sampling, 3) Pregnant or breast feeding. Computerized Randomisation: Two arms (1:1), n = 500 per arm: Arm 1: standard of care. Arm 2: standard of care and Procalcitonin guided diagnostics and treatment of infection. Primary Trial Objective: To address whether daily Procalcitonin measurements and immediate diagnostic and therapeutic response on day-to-day changes in procalcitonin can reduce the mortality of critically ill patients.Discussion: For the first time ever, a mortality-endpoint, large scale randomized controlled trial with a biomarker-guided strategy compared to the best standard of care, is conducted in an Intensive care setting. Results will, with a high statistical power answer the question: Can the survival of critically ill patients be improved by actively using biomarker procalcitonin in the treatment of infections? 700 critically ill patients are currently included of 1000 planned (June 2008). Two interim analyses have been passed without any safety or futility issues, and the third interim analysis is soon to take place. Trial registration number at clinicaltrials.gov: Id. nr.: NCT00271752). [ABSTRACT FROM AUTHOR]

Background: The Surgical Apgar Score is a simple outcome score based on intraoperative parameters. The scoring system is recently validated in patients undergoing esophagectomy but without comparable results. This study evaluated the ability of the original and modified Surgical Apgar Scores to predict major complications in a patient population undergoing Ivor-Lewis esophagectomy., Methods: We retrospectively examined 234 patients who successfully underwent Ivor-Lewis esophagectomy at Rigshospitalet, Copenhagen from November 23, 2011 till November 23, 2014. Major complications were defined as Clavien-Dindo grade IIIa or higher within 30 days after surgery. Univariate and multivariate analyses were performed to assess factors associated with major complications. Receiver operating characteristics were performed for determination of the predictive value of the Surgical Apgar Score scoring systems., Results: There were 64 (27.4%) patients with at least one major complication and 4 (1.7%) deaths. The original and modified versions of the Surgical Apgar Score were not associated with major complications and the scoring systems showed no significant predictive value when receiver operating characteristics were performed., Conclusions: The original or modified versions of the Surgical Apgar Score could possibly be useful in some subgroups of esophagectomy patients, but should not be considered to have a general predictive value. J. Surg. Oncol. 2017;115:186-191. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background: Gly16arg polymorphism of the adrenergic β2-receptor is associated with the elevated cardiac output (Q) in healthy gly16-homozygotic subjects. We questioned whether this polymorphism also affects Q and regional cerebral oxygen saturation (SCO2) during anesthesia in vascular surgical patients., Methods: One hundred sixty-eight patients (age 71 ± 6 years) admitted for elective surgery were included. Cardiovascular variables were determined before and during anesthesia by intravascular pulse contour analysis (Nexfin) and SCO2 by cerebral oximetry (INVOS 5100C). Genotyping was performed with the TaqMan assay., Results: Before anesthesia, Q and SCO2 were 4.7 ± 1.2 L/min and 66% ± 8%, respectively, and linearly correlated (r = 0.35, P < .0001). In patients with the gly16gly genotype baseline, Q was approximately 0.4 L/min greater than in arg16 carriers (CI95: 0.0-0.8, Pt test = .03), but during anesthesia, the difference was 0.3 L/min (Pmixed-model = .07). Post hoc analysis revealed the change in SCO2 from baseline to the induction of anesthesia to be on average 2% greater in gly16gly homozygotes than in arg16 patients when adjusted for the change in Q (P = .03; CI95: 0.2-4.0%)., Conclusions: This study suggests that the β2-adrenoceptor gly16gly genotype is associated with the elevated resting Q. An interesting trend to greater frontal lobe oxygenation at induction of anesthesia in patients with gly16gly genotype was found, but because of insufficient sample size and lack of PCO2 control throughout the measurements, the presented data may only serve as the hypothesis generating for future studies. The confidence limits indicate that the magnitude of the effects may range from clinically insignificant to potentially important.

Background: The purpose of this study was to determine whether anesthesia affects graft patency after lower extremity arterial in situ bypass surgery., Methods: This investigation was a retrospective study using a national database on vascular surgical patients at a single medical institution. We assessed a total of 822 patients exposed to infrainguinal in situ bypass vascular surgery over the period of January 2000 to September 2010., Results: All patients included in the study (age [mean ± SD] 70.8 ± 9.7 years) underwent infrainguinal in situ bypass (n = 885) for lower extremity revascularization under epidural (n = 386) or general (n = 499) anesthesia. Thirty-day mortality (3.4% for epidural anesthesia versus 4.4% general anesthesia; P = 0.414) and comorbidity were comparable in the 2 groups. Graft occlusion within 7 days after surgery was reported in 93 patients, with a similar incidence in the epidural (10.1%) and general (10.8%) anesthesia groups (P = 0.730). When examining a subgroup of patients (n = 242) exposed to surgery on smaller vessels (femorodistal in situ bypass procedures, n = 253), the incidence of graft occlusion was also similar in the 2 groups at 14.0% and 9.4%, respectively (P = 0.262)., Conclusion: This retrospective study has shown that when graft patency is evaluated 7 days after surgery, anesthetic choice (epidural or general anesthesia) does not influence outcome., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background. The prone position is applied to facilitate surgery of the back and to improve oxygenation in the respirator-treated patient. In particular, with positive pressure ventilation the prone position reduces venous return to the heart and in turn cardiac output (CO) with consequences for cerebral blood flow. We tested in healthy subjects the hypothesis that rotating the head in the prone position reduces cerebral blood flow. Methods. Mean arterial blood pressure (MAP), stroke volume (SV), and CO were determined, together with the middle cerebral artery mean blood velocity (MCA V(mean)) and jugular vein diameters bilaterally in 22 healthy subjects in the prone position with the head centered, respectively, rotated sideways, with and without positive pressure breathing (10 cmH(2)O). Results. The prone position reduced SV (by 5.4 ± 1.5%; P < 0.05) and CO (by 2.3 ± 1.9 %), and slightly increased MAP (from 78 ± 3 to 80 ± 2 mmHg) as well as bilateral jugular vein diameters, leaving MCA V(mean) unchanged. Positive pressure breathing in the prone position increased MAP (by 3.6 ± 0.8 mmHg) but further reduced SV and CO (by 9.3 ± 1.3 % and 7.2 ± 2.4 % below baseline) while MCA V(mean) was maintained. The head-rotated prone position with positive pressure breathing augmented MAP further (87 ± 2 mmHg) but not CO, narrowed both jugular vein diameters, and reduced MCA V(mean) (by 8.6 ± 3.2 %). Conclusion. During positive pressure breathing the prone position with sideways rotated head reduces MCA V(mean) ~10% in spite of an elevated MAP. Prone positioning with rotated head affects both CBF and cerebrovenous drainage indicating that optimal brain perfusion requires head centering.

Introduction: Proper training to improve safety of NAPS (nurse-administered propofol sedation) is essential., Objective: To communicate our experience with a training program of NAPS., Materials and Methods: In 2007, a training program was introduced for endoscopists and endoscopy nurses in collaboration with the Department of Anaesthesiology. During a 2.5-year period, eight nurses were trained. Propofol was given as monotherapy. The training program for nurses consisted of a 6-week course including theoretical and practical training whereas the training program for endoscopists consisted of 2.5 h of theory. Patients were selected based on strict criteria including patients in ASA (American Society of Anesthesiologists) group I-III., Results: 2527 patients undergoing 2.656 gastrointestinal endoscopic procedures were included. The patients were ASA group I, II and III in 34.7%, 56% and 9,3%, respectively. Median dose of propofol was 300 mg. No mortality was noted. 119 of 2527 patients developed short lasting hypoxia (4.7%); 61 (2.4%) needed suction; 22 (0.9%) required bag-mask ventilation and 8 (0.3%) procedures had to be discontinued. In 11 patients (0.4%), anesthetic assistance was called due to short lasting desaturation. 34 patients (1.3%) experienced a change in blood pressure greater than 30%., Conclusion: NAPS provided by properly trained nurses according to the present protocol is safe and only associated with a minor risk (short lasting hypoxia 4.7%). National or international structured training programs are at present few or non-existing. The present training program has documented its value and is suggested as the basis for the current development of guidelines.

The concept of cancer stem cells is generally accepted in different malignancies. We have previously shown that the MDA-MB231 breast cancer cells were more radiation resistant when sorted for the two stem cell markers CD24 and ESA. In this study, we examined a possible mechanism that might underlie this phenotype by looking at cell cycle profile and the effect this has on DNA repair pathways. The cell cycle profile showed that there were more CD24(-) ESA(+) sorted MDA-MB231 cells in the S- and G(2)-phases compared with the unsorted cells, 60 and 38% respectively. Cyclin D and E protein levels supported the cell cycle profile and highlighted the possible involvement of homologous recombination (HR) repair in the radioresistant phenotype. To further support this, CD24(-) ESA(+) sorted MDA-MB231 cells demonstrated statistically significant more RAD51 and less γ-H2AX foci 2 h post 4Gy ionising radiation, compared with the unsorted population. Inhibition of the HR pathway effectively sterilised the CD24(- ) ESA(+) sorted MDA-MB231 cells but had no effect on the unsorted cells or MDA468 control breast cancer cell line. Although the changes we saw were specific to MDA-MB231, these results merit further investigation and can be crucial in identifying a mechanism responsible for cancer stem cells treatment resistance in primary tumors.

This case report describes postoperative, reversible renal dysfunction and hypertension in a 5-year-old healthy boy after administration of relevant doses of ketorolac during anaesthesia. Two days postoperatively, the boy presented with polyuria, polydipsia, proteinuria, microscopic haematuria, and hypertension. He was treated with nifedipine. After six months the blood pressure and azotaemia parameters had normalised and antihypertensive treatment was discontinued.

Introduction: In non-habituated subjects, cold-shock response to cold-water immersion causes rapid reduction in cerebral blood flow velocity (approximately 50%) due to hyperventilation, increasing risk of syncope, aspiration, and drowning. Adaptation to the response is possible, but requires several cold immersions. This study examines whether thorough instruction enables non-habituated persons to attenuate the ventilatory component of cold-shock response., Methods: There were nine volunteers (four women) who were lowered into a 0 degrees C immersion tank for 60 s. Middle cerebral artery mean velocity (CBFV) was measured together with ventilatory parameters and heart rate before, during, and after immersion., Results: Within seconds after immersion in ice-water, heart rate increased significantly from 95 +/- 8 to 126 +/- 7 bpm (mean +/- SEM). Immersion was associated with an elevation in respiratory rate (from 12 +/- 3 to 21 +/- 5 breaths, min(-1)) and tidal volume (1022 +/- 142 to 1992 +/- 253 ml). Though end-tidal carbon dioxide tension decreased from 4.9 +/- 0.13 to 3.9 +/- 0.21 kPa, CBFV was insignificantly reduced by 7 +/- 4% during immersion with a brief nadir of 21 +/- 4%., Discussion: Even without prior cold-water experience, subjects were able to suppress reflex hyperventilation following ice-water immersion, maintaining the cerebral blood flow velocity at a level not associated with impaired consciousness. This study implies that those susceptible to accidental cold-water immersion could benefit from education in cold-shock response and the possibility of reducing the ventilatory response voluntarily.

Knowledge of the pathophysiology in accidental hypothermia is essential for clinical decision-making. The prognosis should be favourable provided the condition is recognized and treated accordingly. Progressive organ dysfunction is associated with a declining core temperature which is reversible on rewarming. Other reactions occur during rewarming of which rewarming collapse has received much attention. More detailed knowledge of rewarming collapse which has come out is examined in this paper.

Objective: The purpose of this study was to assess the long-term survival after OHCA., Methods: All OHCA-calls where the Copenhagen Mobile Emergency Care Unit (MECU) was involved from 1994 to1998 are included in this study. Data were collected prospectively. Data on long-term survival was obtained from the Danish Causes of Death Registry and the Danish Civil Registration System. We conducted a search to find out whether patients were still alive on 31 January 2005., Results: Resuscitation was indicated and attempted in 1095 cases and 95 patients (8.7%) survived to discharge. Of these 75% had an initial rhythm of VF, 13% had asystole, 10% had PEA and 2% were unknown. Survival was 87% after one year and survival after 10 years was 46% with a significantly lower survival for patients over 60 years., Conclusion: Long-term survival after out-of-hospital cardiac arrest in a physician-staffed emergency system was comparable to survival after myocardial infarction with 46% being alive after ten years.

Introduction: Near-drowning incidents and drowning deaths after accidental immersion in open waters have been linked to cold shock response. It consists of inspiratory gasps, hyperventilation, tachycardia, and hypertension in the first 2-3 min of cold-water immersion. This study explored the immediate changes in cerebral blood flow velocity (Vmean) during cold-water immersion since cold shock induced hyperventilation may diminish Vmean and lead to syncope and drowning., Methods: There were 13 male volunteers who were lowered into a 0 degrees C immersion tank for 30 s. Vmean in the middle cerebral artery (MCA) was measured together with ventilatory parameters and heart rate before, during, and after immersion., Results: Within seconds after immersion in ice water, heart rate increased from 74 +/- 16 to 107 +/- 18 bpm (mean +/- SD; p < 0.05). Immersion was associated with a marked elevation in respiratory rate (from 16 +/- 3 to 38 +/- 14 breaths x min(-1)) and tidal volume (883 +/- 360 to 2292 +/- 689 ml). The end-tidal carbon dioxide tension decreased from 38 +/- 4 to 26 +/- 5 mmHg and MCA Vmean dropped by 43 +/- 8%. Signs of imminent syncope (drowsiness, blurred vision, loss of responsiveness) were shown by two subjects (MCA Vmean dropped 62% and 68%, respectively)., Discussion: Following ice-water immersion, hyperventilation induced a marked reduction in MCA Vmean to a level which has been associated with disorientation and loss of consciousness.

Introduction: Postoperative urinary retention can cause serious complications. An ultrasound bladderscanner has been shown to be useful in distinguishing between patients who need catheterisation and patients who do not. We wished to investigate if clinical assessment including inspection, percussion and palpation of the bladder is of any use in this perspective. In this study we compare clinical findings with ultrasound examinations., Material and Methods: Two trained doctors each investigated 25 postoperative patients clinically immediately after ultrasound examination in the recovery room. Ultrasound examination was carried out by trained nurses using BladderScan BVI 3000. Assessed and measured volumes as well as patient height, weight, asa-class and sex were registered., Results: We found a high negative predictive value of 92% for a cut-off limit of 500 ml. The corresponding positive predictive value was a modest 38%. This tendency was seen for cut-off-limits exceeding 300 ml., Conclusion: Clinical assessment of bladder size might be useful in terms of ruling out a big volume postoperatively. Because of the low positive predictive value, we recommend verifying urinary retention judged by clinical assessment with ultrasound examination before catheterisation. Also, one has to remember that urinary retention occurs with different volumes in different patients.

In a recent boat accident, a 25-year-old yachting enthusiast fell overboard and survived for 24 hours in 17 degrees C water. Existing survival models are discussed in this case report. There is a discrepancy regarding survival probability amongst the various models. The calculated survival time for the yachtsman ranges from 3 hours to more than 30 hours. A reliable survival-time model is needed to determine the appropriate search duration of rescue services. In this case, the majority of the models underestimated the actual survival time.

This survey addresses the immediate physiological reactions to immersion in cold water: cold shock response, diving reflex, cardiac arrhythmias and hypothermia. Cold shock response is the initial sympathetic reaction to immersion in cold water. The diving reflex is elicited by submersion of the face. Afferent and efferent nerves are the trigeminal and vagal nerves. Cardiac arrhythmias occur immediately after immersion. If the immersion persists, hypothermia becomes an issue. Hypothermia is delayed by habituation to immersion in cold water as well as insulating garments, subcutaneous fat and a large lean body mass.