Complement Profiles in Patients with Amyotrophic Lateral Sclerosis: A Prospective Observational Cohort Study.

BACKGROUND: The complement system has been suggested to be involved in the pathophysiology of amyotrophic lateral sclerosis (ALS), a progressive motor neuron disease. In the present study, we compared levels of selected complement markers to clinical outcome in ALS patients. METHODS: This observational, explorative cohort study included 92 ALS patients, 61 neurological controls (NCs) admitted for suspected aneurysmal subarachnoid haemorrhage, and 96 neurologically healthy controls (NHCs). Peripheral blood and cerebrospinal fluid (CSF) were obtained for the measurement of ficolin-1, -2, and -3; collectin-11, MBL, MASP-3, MAP-1, C4, C3, PTX-3, and complement activation products C4c, C3bc, and sC5b-9. We recorded clinical outcomes of ALS patients for 24 to 48 months after inclusion in order to analyse the effects of the complement markers on survival time. RESULTS: Compared with both control groups, ALS patients exhibited increased collectin-11, C4 and sC5b-9 in plasma, as well as increased ficolin-3 in CSF. Ficolin-2 was significantly decreased in plasma of the ALS patients compared with NHCs, but not with NCs. The concentration of collectin-11, C3 and C3bc correlated negatively with the revised ALS functional rating scale (ALSFRS-R). No association was found between levels of complement markers and survival as estimated by hazard ratios. CONCLUSION: ALS patients exhibit aberrant expression of selected mediators of the lectin complement pathway as well as increased activation of the terminal complement pathway, corroborating the notion that the complement system might be involved in the pathophysiology of ALS.

Prediction of survival in amyotrophic lateral sclerosis: a nationwide, Danish cohort study.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease with great heterogeneity. Biological prognostic markers are needed for the patients to plan future supportive treatment, palliative treatment, and end-of-life decisions. In addition, prognostic markers are greatly needed for the randomization in clinical trials. OBJECTIVE: This study aimed to test the ALS Functional Rating Scale-Revised (ALSFRS-R) progression rate (ΔFS) as a prognostic marker of survival in a Danish ALS cohort. METHODS: The ALSFRS-R score at test date in association with duration of symptoms, from the onset of symptoms until test date, (defined as ΔFS') was calculated for 90 Danish patients diagnosed with either probable or definite sporadic ALS. Median survival time was then estimated from the onset of symptoms until primary endpoint (either death or tracheostomy). ΔFS' was subjected to survival analysis using Cox proportional hazards modelling, log-rank test, and Kaplan-Meier survival analysis. RESULTS AND CONCLUSIONS: Both ΔFS' and age was found to be strong predictors of survival of the Danish ALS cohort. Both variables are easily obtained at the time of diagnosis and could be used by clinicians and ALS patients to plan future supportive and palliative treatment. Furthermore, ΔFS', is a simple, prognostic marker that predicts survival in the early phase of disease as well as at later stages of the disease.

Amyotrophic lateral sclerosis and the innate immune system: protocol for establishing a biobank and statistical analysis plan.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a devastating, progressive disease that causes degeneration of the motor neurons leading to paresis of the bulbar and the skeletal musculature. The pathogenesis of ALS remains unknown. We will test the hypothesis that the complement system is involved in the pathophysiology of ALS. This protocol article describes our efforts to establish a national Danish ALS biobank. The primary aim is to obtain biological material from patients with ALS for the current study as well as for future studies. METHODS AND ANALYSIS: We intend to establish an observational ALS biobank; some of the material from this biobank will be used for a prospective, observational case-control study. The participants are patients with ALS, neurologically healthy controls and non-ALS neurological controls. Each participant consents to be interviewed and to donate blood and cerebrospinal fluid to the biobank. Analysis of the complement system will be carried out on the three groups of patients and compared. ETHICS AND DISSEMINATION: The project has been approved by the Committees on Health Research Ethics in the Capital Region of Denmark (Approval number H-16017145) and the Danish Data Protection Agency (file number 2012-58-0004). All results will be published in peer-reviewed, medical journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: NCT02869048.

Continuous EEG Monitoring in a Consecutive Patient Cohort with Sepsis and Delirium.

BACKGROUND: Delirium is common during sepsis, although under-recognized. We aimed to assess the value of continuous electroencephalography (cEEG) to aid in the diagnosis of delirium in septic patients. METHODS: We prospectively evaluated 102 consecutive patients in a medical intensive care unit (ICU), who had sepsis or septic shock, without evidence of acute primary central nervous system disease. We initiated cEEG recording immediately after identification. The median cEEG time per patient was 44 h (interquartile range 21-99 h). A total of 6723 h of cEEG recordings were examined. The Confusion Assessment Method for the ICU (CAM-ICU) was administered six times daily to identify delirium. We analyzed the correlation between cEEG and delirium using 1252 two-minute EEG sequences recorded simultaneously with the CAM-ICU scorings. RESULTS: Of the 102 included patients, 66 (65%) had at least one delirium episode during their ICU stay, 30 (29%) remained delirium-free, and 6 (6%) were not assessable due to deep sedation or coma. The absence of delirium was independently associated with preserved high-frequency beta activity (> 13 Hz) (P < 10-7) and cEEG reactivity (P < 0.001). Delirium was associated with preponderance of low-frequency cEEG activity and absence of high-frequency cEEG activity. Sporadic periodic cEEG discharges occurred in 15 patients, 13 of whom were delirious. No patient showed clinical or electrographic evidence of non-convulsive status epilepticus. CONCLUSIONS: Our findings indicate that cEEG can help distinguish septic patients with delirium from non-delirious patients.

Amyotrophic lateral sclerosis: The complement and inflammatory hypothesis.

Amyotrophic lateral sclerosis (ALS) is a devastating, neurodegenerative motor neuron disease. The aetiology of ALS remains an enigma which hinders the design of an effective treatment to prevent, postpone, or reverse the pathophysiological changes occurring during the aggressive progression of this disease. During the last decade, basic research within the innate immune system, and in particular the complement system, has revealed new, important roles of the innate immune system during development, homeostasis, and ageing within as well as outside the central nervous system. Several lines of evidence indicate that aberrant activation of the complement system locally in the central nervous system as well as systemically may be involved in the pathophysiology of ALS. This exciting new knowledge could point towards the innate immune system as a potential target of medical intervention in ALS. Recently, the historic perception of ALS as a central neurodegenerative disease has been challenged due to the significant amount of evidence of a dying-back mechanism causing the selective destruction of the motor neurons, indicating that disease onset occurs outside the borders of the blood-brain-barrier. This review addresses the function of the innate immune system during ALS. We emphasize the role of the complement system and specifically suggest the involvement of ficolin-3 from the lectin pathway in the pathophysiology of ALS.

Transorbital impalement by a wooden stick in a 3-year-old child.

We present a case of a 3-year-old girl with a transorbital impalement injury due to a wooden stick penetrating the lower inferior palpebra and progressing through the orbita, after the child jumped from a table and hit a wooden basket containing pieces of exposed stick. CT revealed the stick progressing transorbitally through the medial wall and terminating just below the sella turcica. The stick was successfully removed by neurosurgical and ophthalmological specialists. The eye was subsequently inspected, and showed no pathological findings. The girl was treated with topical chloramphenicol and discharged 2 days later. Follow-up examination 2 months after the trauma demonstrated normal visual acuity and ocular motility, with no diplopia, tearing or pain.

[Treatment of benzodiazepine-resistant alcohol withdrawal symptoms]. / Behandling af benzodiazepinresistente alkoholabstinenssymptomer.

Alcohol withdrawal symptoms can lead to severe morbidity and potentially be fatal if untreated. A subgroup of patients treated for alcohol withdrawal symptoms will exhibit symptoms resistant to first-line treatment with benzodiazepines. The understanding of benziodiazepine-resistant alcohol withdrawal symptoms has increased with new knowledge of implicated neuroreceptors and possible treatment methods. This article aims to elucidate the patient population and the existing methods of treatment.

Glucocorticoid-induced myopathy in the intensive care unit.

Glucocorticoids (GC) are used for intensive care unit (ICU) patients on several indications. We present a patient who was admitted to the ICU due to severe respiratory failure caused by bronchospasm requiring mechanical ventilation and treated with methylprednisolone 240 mg/day in addition to antibiotics and bronchiolytics. When the sedation was lifted on day 10, the patient was awake but quadriplegic. Blood samples revealed elevated muscle enzymes, electromyography showed myopathy, and a muscle biopsy was performed. Glucocorticoid-induced myopathy was suspected, GC treatment was tapered, and muscle strength gradually returned. The patient made full recovery from the quadriplegia a few months later.

Retinal hemodynamic oxygen reactivity assessed by perfusion velocity, blood oximetry and vessel diameter measurements.

PURPOSE: To test the oxygen reactivity of a fundus photographic method of measuring macular perfusion velocity and to integrate macular perfusion velocities with measurements of retinal vessel diameters and blood oxygen saturation. METHODS: Sixteen eyes in 16 healthy volunteers were studied at two examination sessions using motion-contrast velocimetry and retinal oximetry with vessel diameter corrections. To test oxygen reactivity, participants were examined during normoxia, after 15 min of hyperoxia and finally after 45 min of normoxia. Repeatability was assessed by intraclass correlation coefficients (ICC) and limits of agreement. RESULTS: Fifteen minutes of hyperoxia was accompanied by mean reductions in arterial and venous perfusion velocities of 14% and 16%, respectively (p = 0.0080; p = 0.0019), constriction of major arteries and veins by 5.5% and 8.2%, respectively (p < 0.0001), increased retinal arterial oxygen saturation from 95.1 ± 5.0% to 96.6 ± 6.4% (p = 0.038) and increased retinal venous oxygen saturation from 62.9 ± 6.7% to 70.3 ± 7.8% (p = 0.0010). Parameters returned to baseline levels after subsequent normoxia. Saturation and vessel diameter ICCs were 0.88-0.98 (range). For perfusion velocities, short-term ICCs were 0.79-0.82 and long-term ICCs were 0.06-0.11. Intersession increases in blood glucose were associated with reductions in perfusion velocities (arterial p = 0.0067; venous p = 0.018). CONCLUSION: Oxygen reactivity testing supported that motion-contrast velocimetry is a valid method for assessing macular perfusion. Results were consistent with previous observations of hyperoxic blood flow reduction using blue field entoptic and laser Doppler velocimetry. Retinal perfusion seemed to be regulated around individual set points according to blood glucose levels. Multimodal measurements may provide comprehensive information about retinal metabolism.

Invasive Candida infections and the harm from antibacterial drugs in critically ill patients: data from a randomized, controlled trial to determine the role of ciprofloxacin, piperacillin-tazobactam, meropenem, and cefuroxime.

OBJECTIVE: Use of antibiotics in critically ill patients may increase the risk of invasive Candida infection. The objective of this study was to determine whether increased exposure to antibiotics is associated with increased prevalence of invasive Candida infection. DESIGN: Substudy using data from a randomized controlled trial, the Procalcitonin And Survival Study 2006-2010. SETTING: Nine multidisciplinary ICUs across Denmark. PATIENTS: A total of 1,200 critically ill patients. INTERVENTION: Patients were randomly allocated to either a "high exposure" antibiotic therapy (intervention arm, n = 604) or a "standard exposure" guided by current guidelines (n = 596). MEASUREMENTS AND MAIN RESULTS: Seventy-four patients met the endpoint, "invasive Candida infection," 40 in the high exposure arm and 34 in standard exposure arm (relative risk = 1.2; 95% CI, 0.7-1.8; p = 0.52). Among medical patients in the high exposure arm, the use of ciprofloxacin and piperacillin/tazobactam was 51% and 75% higher than in the standard exposure arm; no difference in antibiotic exposure was observed between the randomized arms in surgical patients. Among medical intensive care patients, invasive Candida infection was more frequent in the high exposure arm (6.2%; 27/437) than in standard exposure arm (3.3%; 14/424) (hazard ratio = 1.9; 95% CI, 1.0-3.6; p = 0.05). Ciprofloxacin used at study entry independently predicted invasive Candida infection (adjusted hazard ratio = 2.1 [1.1-4.1]); the risk gradually increased with duration of ciprofloxacin therapy: six of 384 in patients not exposed (1.6%), eight of 212 (3.8%) when used for 1-2 days (hazard ratio = 2.5; 95% CI, 0.9-7.3), and 31 of 493 (6.3%) when used for 3 days (hazard ratio = 3.8; 95% CI, 1.6-9.3; p = 0.002). Patients with any ciprofloxacin-containing antibiotic regimen the first 3 days in the trial had a higher risk of invasive Candida infection than did patients on any antibiotic regimen not containing ciprofloxacin (unadjusted hazard ratio = 3.7; 95% CI, 1.6-8.7; p = 0.003; adjusted hazard ratio, 3.4; 95% CI, 1.4-8.0; p = 0.006). CONCLUSIONS: High exposure to antibiotics is associated to increased risk of invasive Candida infection in medical intensive care patients. Patients with ciprofloxacin-containing regimens had higher risk of invasive Candida infection. Other antibiotics, such as meropenem, piperacillin/tazobactam, and cefuroxime, were not associated with such a risk.

[Oesophageal perforation of osteosynthesis material after anterior cervical surgery].

The rare, potentially life-threatening complication to anterior cervical surgery, oesophageal perforation, occurs after surgical trauma or due to erosion by migrating hardware. Symptoms are hoarseness, dysphagia, neck/throat pain, subcutaneous emphysema and fever. Imaging and endoscopic diagnosis can give false negative results. We present a case of a 74-year-old male, who was readmitted with sepsis and abscess in the operation area three weeks after anterior cervical surgery. Veillonella parvula was found in the abscess material and computed tomography confirmed the diagnosis of oesophageal perforation.

[Tension haemothorax after removal of pleural pigtail catheter]. / Udvikling af trykhæmothorax efter seponering af pleuralt beliggende grisehalekateter

Today, standard treatment of pleural effusion is ultrasound guided insertion of a pleural pigtail catheter. This procedure is known to have a low complication rate, but complications as pneumothorax, haemorrhage and infection are occurring. The most frequent complications are seen at the time of insertion. We present a case of a 68-year-old woman in the intensive care unit with normal coagulation status who after an uneventful removal of a pleural pigtail catheter developed a tension haemothorax requiring acute evacuation.

Detection and quantification of Flavobacterium psychrophilum-specific bacteriophages in vivo in rainbow trout upon oral administration: implications for disease control in aquaculture.

The use of bacteriophages in the treatment and prevention of infections by the fish pathogen Flavobacterium psychrophilum has attracted increased attention in recent years. It has been shown recently that phage delivery via the parenteral route resulted in immediate distribution of phages to the circulatory system and the different organs. However, little is known about phage dispersal and survival in vivo in rainbow trout after delivery via the oral route. Here we examined the dispersal and survival of F. psychrophilum phage FpV-9 in vivo in juvenile rainbow trout after administration by three different methods-bath, oral intubation into the stomach, and phage-coated feed-with special emphasis on the oral route of delivery. Phages could be detected in all the organs investigated (intestine, spleen, brain, and kidney) 0.5 h postadministration, reaching concentrations as high as ∼10(5) PFU mg intestine(-1) and ∼10(3) PFU mg spleen(-1) within the first 24 h following the bath and ∼10(7) PFU mg intestine(-1) and ∼10(4) PFU mg spleen(-1) within the first 24 h following oral intubation. The phages were most persistent in the organs for the first 24 h and then decreased exponentially; no phages were detected after 83 h in the organs investigated. Phage administration via feed resulted in the detection of phages in the intestine, spleen, and kidney 1 h after feeding. Average concentrations of ∼10(4) PFU mg intestine(-1) and ∼10(1) PFU mg spleen(-1) were found throughout the experimental period (200 h) following continuous delivery of phages with feed. These experiments clearly demonstrate the ability of the phages to survive passage through the fish stomach and to penetrate the intestinal barrier and enter the circulatory system after oral delivery, although the quantity of phages found in the spleen was 100- to 1,000-fold lower than that in the intestine. It was also shown that phages could tolerate long periods of desiccation on the feed pellets, with 60% survival after storage at -80°C, and 10% survival after storage at 5°C, for ∼8 months. Continuous delivery of phages via coated feed pellets constitutes a promising method of treatment and especially prevention of rainbow trout fry syndrome.

Use of propofol infusion in alcohol withdrawal-induced refractory delirium tremens.

INTRODUCTION: Delirium tremens is a potentially fatal complication of alcohol withdrawal. In severe delirium, very large dosages of benzodiazepines can be required and in refractory cases, sedation with propofol can be used. Treatment of refractory delirium tremens with propofol is mainly described in case reports. We aimed to evaluate the treatment of delirium tremens with propofol infusion for 48 h. MATERIAL AND METHODS: This study was a single-centre retrospective cohort analysis of 15 patient journals covering the period from May 2012 to September 2013. RESULTS: Five women and ten men were included. Their mean age was 50.9 years. Prior to propofol treatment, conventional treatment with up to 1,500 mg of benzodiazepines, 2,000 mg of chlordiazepoxide or 1,200 mg of phenobarbital was attempted in the medical or psychiatric ward, without effect (sleep). Patients were sedated, intubated and mechanically ventilated in the intensive care unit. The mean propofol infusion rate was 4.22 mg/kg/h. Thirteen patients received supplemental infusion of opioids, whereas seven required concomitant vasopressor infusion. Once propofol infusion was discontinued after 48 h, 12 patients had a long awakening, displaying symptoms of prolonged sedation. Twelve of the 15 patients treated for delirium tremens with propofol for 48 h were successfully treated. Three patients needed further treatment. CONCLUSION: Our study suggests that treatment with propofol is viable. Establishing indication, dose, duration, and long-term effects of propofol treatment of delirium tremens requires further investigation. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

The potential of antimicrobials to induce thrombocytopenia in critically ill patients: data from a randomized controlled trial.

BACKGROUND: Antimicrobial-induced thrombocytopenia is frequently described in the literature among critically ill patients. Several antimicrobials have been implicated, although experimental evidence to demonstrate causality is limited. We report, using a randomized trial, the potential of antimicrobials to induce thrombocytopenia. METHODS: Randomized trial allocated patients to antimicrobial treatment according to standard- of-care (SOC group) or drug-escalation in case of procalcitonin increases (high-exposure group). Patients were followed until death or day 28. Thrombocytopenia defined as absolute (platelet count ≤ 100 x 109/L) or relative (≥ 20% decrease in platelet count). Analyses were performed in the two randomized groups and as a merged cohort. RESULTS: Of the 1147 patients with platelet data available, 18% had absolute thrombocytopenia within the first 24 hours after admission to intensive care unit and additional 17% developed this complication during follow-up; 57% developed relative thrombocytopenia during follow-up. Absolute and relative thrombocytopenia day 1-4 was associated with increased mortality (HR: 1.67 [95% CI: 1.30 to 2.14]; 1.71 [95% CI: 1.30 to 2.30], P<0.0001, respectively). Patients in the high-exposure group received more antimicrobials including piperacillin/tazobactam, meropenem and ciprofloxacin compared with the SOC group, whereas cefuroxime was used more frequently in the SOC group (p<0.05). Risk of absolute and relative thrombocytopenia (RR: 0.9 [0.7-1.3], p=0.7439; 1.2 [1.0-1.4], p=0.06; respectively), as well as absolute platelet count (daily difference, high-exposure vs. SOC -1.7 [-3.8-0.5], p=0.14) was comparable between groups. In observational analyses, use of ciprofloxacin and piperacillin/tazobactam predicted risk of relative thrombocytopenia (vs. cefuroxime, RR: 2.08 [1.48-2.92]; 1.44 [1.10-1.89], respectively), however only ciprofloxacin were associated with a reduction in absolute platelet count (p=0.0005). CONCLUSION: High exposure to broad-spectrum antimicrobials does not result in a reduction in thrombocytopenia in critically ill patients. However, single use of ciprofloxacin, and less so piperacillin/tazobactam, may contribute to a lower platelet count. TRIAL REGISTRATION: ClinicalTrials.gov NCT00271752 http://clinicaltrials.gov/ct2/show/NCT00271752.

[Hypoglossus and laryngeal nerves palsy after an intubation for Legionella infection]. / Tunge- og stemmebåndsparese efter endotrakeal intubation for Legionella-pneumoni.

Extracranial involvement of the hypoglossal nerve and recurrent laryngeal branch of the vagal nerve can be a complication of anaesthetic airway management (Tapia's syndrome) or focal involvement due to Legionella infection. We present a patient with bilateral hypoglossal and unilateral recurrent laryngeal nerves palsy after a complicated intubation and a Legionella infection. Clarithromycin therapy was started. Within months, tongue mobility and swallowing gradually improved. Two months after discharge persisting unilateral recurrent nerve palsy was observed.

Treatment of critical illness polyneuropathy and/or myopathy - a systematic review.

INTRODUCTION: The objective was to search the literature with a view to providing a general description of critical illness myopathy/polyneuropathy (CIM/CIP), including its genesis and prevention. Furthermore, it was our aim to determine whether new treatments have occurred in the past five years. MATERIAL AND METHODS: PubMed, Cinahl and Swedmed+ were searched using the terms CIM, CIP and intensive care. The search was narrowed by adding the limits: humans, English, Danish, Norwegian, Swedish and, furthermore, articles had to have been published in the past five years as we aimed to focus on new knowledge. RESULTS: A total of 74 articles were found. We excluded articles focusing on children and intensive care, tight insulin therapy in patients without CIM/CIP and articles focusing on Guillain-Barré syndrome, triage, bleeding, alcohol or meningitis. Of the remaining 36 articles, only five focused on CIM/CIP treatment. Their relevant original references were found and used too. CONCLUSION: CIM/CIP is the most commonly occurring intensive care unit (ICU)-acquired neuromuscular dysfunction, and it is associated with a significant increase in length of stay, delayed weaning from mechanical ventilation, prolonged rehabilitation and, consequently, more expenses. To treat/prevent this condition, it seems reasonable to ensure maximal functional status for survivors of an ICU-stay by applying a multimodal therapeutic approach that includes intensive insulin therapy, minimal sedation and, as suggested by new evidence, early physiotherapy and electrical muscle stimulation.

Kidney failure related to broad-spectrum antibiotics in critically ill patients: secondary end point results from a 1200 patient randomised trial.

OBJECTIVES: To explore whether a strategy of more intensive antibiotic therapy leads to emergence or prolongation of renal failure in intensive care patients. DESIGN: Secondary analysis from a randomised antibiotic strategy trial (the Procalcitonin And Survival Study). The randomised arms were conserved from the primary trial for the main analysis. SETTING: Nine mixed surgical/medical intensive care units across Denmark. PARTICIPANTS: 1200 adult intensive care patients, 18+ years, expected to stay +24 h. EXCLUSION CRITERIA: bilirubin >40 mg/dl, triglycerides >1000 mg/dl, increased risk from blood sampling, pregnant/breast feeding and psychiatric patients. INTERVENTIONS: Patients were randomised to guideline-based therapy ('standard-exposure' arm) or to guideline-based therapy supplemented with antibiotic escalation whenever procalcitonin increased on daily measurements ('high-exposure' arm). MAIN OUTCOME MEASURES: Primary end point: estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2). Secondary end points: (1) delta eGFR after starting/stopping a drug and (2) RIFLE criterion Risk 'R', Injury 'I' and Failure 'F'. Analysis was by intention to treat. RESULTS: 28-day mortality was 31.8% and comparable (Jensen et al, Crit Care Med 2011). A total of 3672/7634 (48.1%) study days during follow-up in the high-exposure versus 3016/6949 (43.4%) in the 'standard-exposure arm were spent with eGFR <60 ml/min/1.73 m(2), p<0.001. In a multiple effects model, 3 piperacillin/tazobactam was identified as causing the lowest rate of renal recovery of all antibiotics used: 1.0 ml/min/1.73 m(2)/24 h while exposed to this drug (95% CI 0.7 to 1.3 ml/min/1.73 m(2)/24 h) vs meropenem: 2.9 ml/min/1.73 m(2)/24 h (2.5 to 3.3 ml/min/1.73 m(2)/24 h)); after discontinuing piperacillin/tazobactam, the renal recovery rate increased: 2.7 ml/min/1.73 m(2)/24 h (2.3 to 3.1 ml/min/1.73 m(2) /24 h)). eGFR <60 ml/min/1.73 m(2) in the two groups at entry and at last day of follow-up was 57% versus 55% and 41% versus 39%, respectively. CONCLUSIONS: Piperacillin/tazobactam was identified as a cause of delayed renal recovery in critically ill patients. This nephrotoxicity was not observed when using other beta-lactam antibiotics. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00271752.

[Acute compartment syndrome following a total knee arthroplasty]. / Akut kompartmentsyndrom efter total knæalloplastik.

Acute compartment syndrome is a rare, but severe complication to knee arthroplasty. The main symptoms are extreme pain unrelated to the surgery, pulselessness, and tense and pallid skin. The syndrome can be disguised by an effective pain management, but due to the consequences, an early diagnosis and fasciotomy is important. We describe a case with a patient, who had undergone a total knee arthroplasty and after a postoperative period of 5,5 hours she developed extreme pain in the limb, below the operated knee. The diagnosis was confirmed by sonography, and an acute fasciotomy was performed.

[Pancreatic panniculitis is necrosis of adipocytes in the subcutis followed by intense pain]. / Pankreatisk pannikulitis er nekrose af fedtceller i subcutis ledsaget af intense smerter.

We report an unusual history of pain in a young patient in the intensive care unit. A 33 year-old alcoholic male with acute pancreatitis had generalized intense pain and developed erythema on the lower truncus and the lower extremities. Treatment with different antibiotics, antihistamines and topical potent steroid cream were all ineffective. A biopsy showed necrotic adipocytes characteristic for pancreatic panniculitis. We suggest that pancreatic panniculitis should be considered in patients with erythema, pain and known pancreatic disease.