Coagulopathy as a predictor of mortality after penetrating traumatic brain injury.

STUDY HYPOTHESIS: Traumatic brain injury (TBI) is a leading cause of mortality with penetrating TBI (p-TBI) patients having worse outcomes. These patients are more likely to be coagulopathic than blunt TBI (b-TBI) patients, thus we hypothesize that coagulopathy would be an early predictor of mortality. METHODS: We identified highest-level trauma activation patients who underwent an admission head CT and had ICU admission orders from August 2009-May 2013, excluding those with polytrauma and anticoagulant use. Rapid thrombelastography (rTEG) was obtained after emergency department (ED) arrival and coagulopathy was defined as follows: ACT≥128s, KT≥2.5s, angle≤56°, MA≤55mm, LY-30≥3.0% or platelet count≤150,000/µL. Regression modeling was used to assess the association of coagulopathy on mortality. RESULTS: 1086 patients with head CT scans performed and ICU admission orders were reviewed. After exclusion criteria were met, 347 patients with isolated TBI were analyzed-99 (29%) with p-TBI and 248 (71%) with b-TBI. Patients with p-TBI had a higher mortality (41% vs. 10%, p<0.0001) and a greater incidence of coagulopathy (64% vs. 51%, p<0.003). After dichotomizing p-TBI patients by mortality, patients who died were younger and were more coagulopathic. When adjusting for factors available on ED arrival, coagulopathy was found to be an early predictor of mortality (OR 3.99, 95% CI 1.37, 11.72, p-value=0.012). CONCLUSIONS: This study demonstrates that p-TBI patients with significant coagulopathy have a poor prognosis. Coagulopathy, in conjunction with other factors, can be used to earlier identify p-TBI patients with worse outcomes and represents a possible area for intervention.

The Body Composition Monitor: a flexible tool for routine fluid management across the haemodialysis population.

Bioimpedance measurements with the Body Composition Monitor (BCM) have been shown to improve fluid management in haemodialysis. However, there is a lack of a sufficiently robust evidence-base for use of the BCM outside of standard protocols. This study aims to characterise BCM measurement variation to allow users to make measurements and interpret the results with confidence in a range of clinical scenarios. BCM measurements were made in 48 healthy controls and in 48 stable haemodialysis patients before and immediately after dialysis. The effect of utilising alternative measurement paths was assessed using mixed effects models and the effect of measuring post-dialysis was assessed by comparing changes in BCM-measured overhydration (OH) with weight changes over dialysis. The data from healthy controls suggest that there is no difference in BCM-measured OH between all the whole-body paths other than the foot-to-foot measurement. Dialysis patients showed similar results other than having higher BCM-measured OH when measured across the site of a vascular access. There was good agreement between BCM-measured OH and change in weight, suggesting post-dialysis measurements can be utilised. These results suggest BCM protocols can be flexible regarding measurement paths and timing of measurement to ensure as many patients as possible can benefit from the technology.

Early plasma transfusion is associated with improved survival after isolated traumatic brain injury in patients with multifocal intracranial hemorrhage.

BACKGROUND: Plasma-based resuscitation improves outcomes in trauma patients with hemorrhagic shock, while large-animal and limited clinical data suggest that it also improves outcomes and is neuroprotective in the setting of combined hemorrhage and traumatic brain injury. However, the choice of initial resuscitation fluid, including the role of plasma, is unclear for patients after isolated traumatic brain injury. METHODS: We reviewed adult trauma patients admitted from January 2011 to July 2015 with isolated traumatic brain injury. "Early plasma" was defined as transfusion of plasma within 4 hours. Purposeful multiple logistic regression modeling was performed to analyze the relationship of early plasma and inhospital survival. After testing for interaction, subgroup analysis was performed based on the pattern of brain injury on initial head computed tomography: epidural hematoma, intraparenchymal contusion, subarachnoid hemorrhage, subdural hematoma, or multifocal intracranial hemorrhage. RESULTS: Of the 633 isolated traumatic brain injury patients included, 178 (28%) who received early plasma were injured more severely coagulopathic, hypoperfused, and hypotensive on admission. Survival was similar in the early plasma versus no early plasma groups (78% vs 84%, P = .08). After adjustment for covariates, early plasma was not associated with improved survival (odds ratio 1.18, 95% confidence interval 0.71-1.96). On subgroup analysis, multifocal intracranial hemorrhage was the largest subgroup with 242 patients. Of these, 61 (25%) received plasma within 4 hours. Within-group logistic regression analysis with adjustment for covariates found that early plasma was associated with improved survival (odds ratio 3.34, 95% confidence interval 1.20-9.35). CONCLUSION: Although early plasma transfusion was not associated with improved in-hospital survival for all isolated traumatic brain injury patients, early plasma was associated with increased in-hospital survival in those with multifocal intracranial hemorrhage.

European study on epidemiology and management of hepatitis C virus (HCV) infection in the haemodialysis population. Part 3: prevalence and incidence.

An analysis of the literature showed a high prevalence of HCV in the European dialysis population in the nineties. The prevalence was similar in most countries in northern Europe, but infection was more common in France, Italy, Spain, Portugal and Greece (1) and in Eastern European countries (2). The reported prevalence of anti-HCV-positive patients in the EDTA registry was 21% in 1992 and 18% in 1993 (3) ranging from 1% in Finland to 42% in Egypt (4). The incidence of HCV, in new patients starting renal replacement therapy, ranged from 3% to 7% (5,6) and reported seroconversion rates during dialysis treatment varied between 1% (7) and 16% (8) per year.

Sero-conversion of HCV negative patients: a European study on the epidemiology and management of HCV haemodialysis patients.

This paper reports part of the findings from a larger study reported earlier, the European study on epidemiology and the management of HCV in the haemodialysis population (1). Centres recruited to the larger study were monitored for a further one year observation period to measure and generate a deeper understanding of HCV sero-conversion. From 4724 patients who were studied at the baseline, in 68 centres, only 13 patients were found to have sero-converted. These sero-conversions occurred in 7 hospitals within 5 different countries. Possible routes of transmission and risk factors are described with respect to the individual centres and good practice recommendations based on current evidence presented.

Development of indicators to measure European variation of nursing activities.

This paper describes a study to capture the key roles and activities of nephrology nurses across different countries in Europe. The concept of the study and the need to clarify the activities of the nephrology nurse arose as part of a larger study to develop the European Practice Database (EPD) (1). The Research Board (EDTNA/ERCA) needed to identify key questions that would detect significant differences in the role and responsibilities of nephrology nurses in different countries and monitor the evolution over time of nephrology nursing practice in Europe. It was therefore appropriate to devise a separate small study to generate evidence based questions for the EPD and confirm the reliability and usefulness of the information captured.

Upon admission coagulation and platelet function in patients with thermal and electrical injuries.

RATIONAL: There has been increased focus on hemostatic potential and function in the initial assessment of the patient with traumatic injuries, that not been extensively studied in patients with burns. We proposed to determine the hemostatic potential of patients with burns upon admission to the emergency department and contrasted their condition with that of healthy controls and patients with other traumatic injuries. In addition we assessed differences due to thermal versus electrical injury and evaluated the effect of burn size. METHODS: This is a patient based prospective observational study conducted with delayed consented. Subjects at the highest level of trauma activation upon admission to the ED had a blood sample collected for research purposes and were subsequently consented. Hemostatic potential was measured by rapid thromelastography (r-TEG®), thrombin generation by calibrated automated thrombogram (CAT) and platelet function by Multiplate® using five activators. Burn subjects were compared to subjects with other traumatic injuries and controls. Within the burn subjects additional analysis compared mechanism (thermal vs. electrical) and burn size. Values are medians (IQR). RESULTS: Two hundred and eighty two trauma patients (with burns n=40, 14%) and 27 controls were enrolled. Upon admission, compared to controls, subjects with burns or trauma were hyper-coagulable based on r-TEG and CAT, with increased rates of clot formation and thrombin generation. There were no differences in burns compared to other traumatic injuries. The presence of hyper-coagulation did not appear to be related to the type of burn or the percentage of total body surface area involved. Employing previous defined cut points for R-TEG driven therapeutic interventions burn patients had similar rates of hyper- and hypo-coagulation noted in patients with traumatic injuries. CONCLUSION: Upon admission patients with burns are in a hyper-coagulable state similar to that of other trauma patients. Employing demonstrated cut points of hemostatic potential in trauma patients associated with increased risk of poor outcomes demonstrated the incidence in burn patients to be similar, suggesting that these values could be used in the early assessment of the patient with burns to guide treatment interventions.

Unexpected triggering of the dialysate blood leak detector by haemolysis.

This case showed that it is possible for haemoglobin released by haemolysis in the extracorporeal circuit to pass through a high permeability (albumin retaining) dialyser membrane. In the incident described, the blood leak detector of the dialysis machine was activated before the patient became symptomatic. Haemolysis should be considered as a possible cause of blood leak alarms during dialysis with high flux membranes.

Predicting progressive hemorrhagic injury from isolated traumatic brain injury and coagulation.

BACKGROUND: Progressive hemorrhagic injury (PHI) in traumatic brain injury (TBI) patients is associated with poor outcomes. Early prediction of PHI is difficult yet vital. We hypothesize that TBI subtype and coagulation would be predictors of PHI. METHODS: This was a retrospective analysis of highest level activation adult trauma patients with evidence of TBI (head Abbreviated Injury Scale ≥3). Coagulopathy was determined using rapid thrombelastography (r-TEG), complete blood counts, and conventional coagulation tests obtained on arrival. Patients were dichotomized into PHI and stable groups based on head computerized CT. Subtypes of TBI included subdural hematoma, intraparenchymal contusions (IPC), subarachnoid hemorrhage, epidural hematoma, and combined. Data are reported as median values with interquartile range (IQR). Multivariate logistic regression was used to assess the effect of subtype and coagulation on PHI. RESULTS: We included 279 isolated TBI patients who met study criteria. There were 157 patients (56%) who experienced PHI; 122 (44%) were stable on repeat CT. Patients with PHI were older, had fewer hospital-free days, and higher mortality (all P < .001). No differences were noted in r-TEG parameters between groups; however, coagulopathy and age were independent predictors of progression in all subtypes (odds ratio [OR], 1.81; 95% CI, 1.09-3.01 [P = .021]; OR, 1.02, 95% CI, 1.01-1.04 [P = .006]). Controlling for age, Glasgow Coma Scale score, and coagulopathy, patients with IPC were more likely to experience PHI (OR, 4.49; 95% CI, 2.24-8.98; P < .0001). CONCLUSION: This study demonstrates that older patients with coagulation abnormalities and IPC on admission are more likely to experience PHI, identifying a target population for earlier therapies.

Hormonal control of the cervix in pregnant gilts. III. Relaxin's influence on cervical biochemical properties in ovariectomized hormone-treated pregnant gilts.

The effects of relaxin on the biochemical properties of both the uterine and vaginal portions of the cervix were examined between days 80-110 of pregnancy in ovariectomized gilts given progesterone to maintain pregnancy. In the cervix of control gilts and those ovariectomized and given progesterone plus relaxin, wet and dry weights, water content, and the glycosaminoglycan/collagen ratio increased between days 80-110 of gestation. Collagen concentrations based on wet or dry weight and glycosaminoglycan concentrations based on wet weight decreased during this period. After ovariectomy, there were no changes in these cervical connective tissue components when relaxin was not given. The glycosaminoglycans hyaluronic acid, heparan sulfate, and dermatan sulfate were found in the cervices of all treatment groups, with dermatan sulfate predominating. The ratio of the individual glycosaminoglycans did not change during pregnancy or with treatment. The major dermatan sulfate proteoglycan from the pig cervix was isolated and found to be similar in size, immunoreactivity, amino acid composition, and amino acid sequence to the major dermatan sulfate proteoglycans isolated from the cervices of other mammals. It is concluded that the relaxin-induced changes in the connective tissue composition of the cervix may contribute at least in part to increased extensibility and growth of the cervix during the last third of gestation in pigs.

Leucocyte entry and endothelial E-selectin expression following intradermal Propionibacterium acnes administration.

Immune responses in porcine skin to intradermal inoculation of heat-killed Propionibacterium acnes (HKPA), the major bacterial agent associated with human inflammatory acne, were studied. Pigs were chosen as experimental animals because their skin is similar in structure and composition to that of man and because the use of genetically inbred pigs enables leucocytes to be transferred between animals without eliciting rejection responses. Two pigs were sensitized intradermally with 10 mg of HKPA and were challenged 2 weeks later with doses ranging from 1-100 microg of HKPA in various intradermal sites on the ventral aspect of the abdomen. Four further pigs, previously sensitized with Bacillus Calmette-Guérin (BCG) but not HKPA, were challenged with purified protein derivative (PPD) of bovine tuberculin and HKPA. Entry of(51)Cr-labelled peripheral blood lymphocytes (PBLs) over 48 h was studied in all the challenge sites. Peak PBL entry occurred at 4 h, remaining sustained up to 24 h. There was a dose-dependent effect of HKPA on the level of PBL entry, which was antigen-specific, as few leucocytes were seen in PPD-challenge sites in HKPA-sensitized pigs or in HKPA-challenged sites in BCG-sensitized pigs. There was also a substantial influx of(111)Indium-labelled neutrophils into the lesions. Lymphocytes present were predominantly of the CD3(+)CD2(+)T-cell subset, although gammadelta TCR(+)cells were present also, particularly after 24 h. E-selectin was markedly upregulated on dermal endothelium in the P. acnes sites. The histological infiltration and kinetics were similar to those reported in human inflammatory acne.

CE marking & the MDD: what difference will the new regulations make?

CE marks are symbols used to show that products comply with regulations, or 'Directives', issued by the Council of Ministers of the European Commission. The EC Directives cover all kinds of products, from toys to construction materials. They are intended to make it easier for manufacturers to sell their products throughout the European Community. There will be three directives for medical devices.

Post insertion catheter care in peritoneal dialysis centers across Europe: results of the Post Insertion Project of the Research Board.

The EDTNA/ERCA survey of Post Insertion Catheter Care in Peritoneal Dialysis (PICC) was a project organised through the Collaborative Research Programme (CRP) of the EDTNA/ERCA. In this survey, data were collected from 54 participating centres in 20 countries. From this survey it became clear that there is no standardised approach to immediate post-catheter insertion treatment protocols. If we want to reduce technique failure of PD related to catheter failure, a first step will be to investigate the different policies used in Europe in order to evaluate the outcome results derived from different policies in post insertion catheter care.

Technological advances in renal care.

The first systems for treating kidney failure were developed in the 1940's, when it was found that blood could be successfully cleared of toxins and returned to the body using a relatively simple device based on artificial sausage skin wrapped around a wooden frame. This process was used to replace the function of the kidney, allowing patients to recover from conditions such as poisoning or crush injuries that temporarily stop the kidneys working. In the 1960's, advances in technology made long-term replacement of renal function using haemodialysis machines possible and allowed surgeons to carry out kidney transplants between people who were not identical twins. Long-term peritoneal dialysis became a viable treatment option two decades later. There are now over 1.1 million people world-wide receiving regular dialysis treatment and around 340,000 people living with a donated kidney. This paper reviews the pioneering work in the treatment of kidney failure and looks at some of the recent advances in equipment design, materials science, immunosuppression and information technology that aim to improve the quality of life and the life expectancy for patients living on renal replacement therapy.

Treating and monitoring water for dialysis in Europe.

The quality of water used for dialysis is not subject to any mandatory regulations in most European countries. A survey of haemodialysis facilities in 14 countries carried out by the European Dialysis and Transplant Nurses Association/European Renal Care Association (EDTNA/ERCA) showed that the majority of centres aimed to meet the requirements of the European Pharmacopoeia, but only 50% carried out tests to check compliance. The wide variation in policies for maintaining and monitoring the equipment and the distribution system indicates that guidelines for water treatment are urgently needed in Europe.

Notified bodies. Questions and answers.

Under the new system of regulation, many companies will need to develop working relationships with Notified Bodies to achieve approval to affix the CE mark to their products. This article answers some pertinent questions relating to Notified Bodies in general, and describes the situation in the United Kingdom.

Demonstration of adenosine deaminase activity in human fibroblast lysosomes.

Human fibroblast lysosomes, purified on Percoll density gradients, contain an adenosine deaminase (ADA) activity that accounts for approximately 10% of the total ADA activity in GM0010A human fibroblasts. In assays of lysosomal ADA, the conversion of [3H]adenosine into [3H]inosine was proportional to incubation time and the amount of lysosomal material added to reaction mixtures. Maximal activity was observed between pH 7 and 8, and lysosomal ADA displayed a Km of 37 microM for adenosine at 25 degrees C and pH 5.5. Lysosomal ADA was completely inhibited by 2.5 mM Cu2+ or Hg2+ salts, but not by other bivalent cations (Ba2+, Cd2+, Ca2+, Fe2+, Mg2+, Mn2+ and Zn2+). Coformycin (2.5 mM), deoxycoformycin (0.02 mM), 2'-deoxyadenosine (2.5 mM), 6-methylaminopurine riboside (2.5 mM), 2'-3'-isopropylidene-adenosine (2.5 mM) and erythro-9-(2-hydroxy-3-nonyl)adenine (0.2 mM) inhibited lysosomal ADA by > 97%. In contrast, 2.5 mM S-adenosyl-L-homocysteine and cytosine were poor inhibitors. Nearly all lysosomal ADA activity is eluted as a high-molecular-mass protein (> 200 kDa) just after the void volume on a Sephacryl S-200 column, and is very heat-stable, retaining 70% of its activity after incubation at 65 degrees C for 80 min. We speculate that compartmentalization of ADA within lysosomes would allow deamination of adenosine to occur without competition by adenosine kinase, which could assist in maintaining cellular energy requirements under conditions of nutritional deprivation.