High extracellular potassium and its correlates after severe head injury: relationship to high intracranial pressure

Disturbed ionic and neurotransmitter homeostasis are now recognized to be probably the most important mechanisms contributing to the development of secondary brain swelling after traumatic brian injury (TBI). Evidence obtained from animal models indicates that posttraumatic neuronal excitation via excitatory amino acids leads to an increase in extracellular potassium, probably due to ion channel activation. The purpose of this study was therefore to measure dialysate potassium in severely head injured patients and to correlate these results with intracranial pressure (ICP), outcome, and also with the levels of dialysate glutamate, lactate, and cerebral blood flow (CBF) so as to determine the role of ischemia in this posttraumatic ionic dysfunction. Eighty-five patients with severe TBI (Glasgow Coma Scale score < 8) were treated according to an intensive ICP management-focused protocol. All patients underwent intracerebral microdialyis. Dialysate potassium levels were analyzed by flame photometry, as were dialysate glutamate and dialysate lactate levels, which were measured using high-performance liquid chromatography and an enzyme-linked amperometric method in 72 and 84 patients respectively. Cerebral blood flow studies (stable Xenon--computerized tomography scanning) were performed in 59 patients. In approximately 20% of the patients, potassium values were increased (dialysate potassium > 1.8 mmol). Mean dialysate potassium (> 2 mmol) was associated with ICP above 30 mm Hg and fatal outcome. Dialysate potassium correlated positively with dialysate glutamate (p < 0.0001) and lactate levels (p < 0.0001). Dialysate potassium was significantly inversely correlated with reduced CBF (p = 0.019). Dialysate potassium was increased after TBI in 20% of measurements. High levels of dialysate potassium were associated with increased ICP and poor outcome. The simultaneous increase of potassium, together with dialysate glutamate and lactate, supports the hypothesis that glutamate induces ionic flux and consequently increases ICP due to astrocytic swelling. Reduced CBF was also significantly correlated with increased levels of dialysate potassium. This may be due to either cell swelling or altered potassium reactivity in cerebral blood vessels after trauma.

Anemia during adjuvant non-taxane chemotherapy for early breast cancer: Incidence and risk factors from two trials of the International Breast Cancer Study Group

GOAL OF THE WORK: Anemia is a common side effect of chemotherapy. Limited information exists about its incidence and risk factors. The objective of this study was to evaluate the incidence of anemia and risk factors for anemia occurrence in patients with early breast cancer who received adjuvant chemotherapy. MATERIALS AND METHODS: We evaluated risk factors for anemia in pre- and post/perimenopausal patients with lymph node-positive early breast cancer treated with adjuvant chemotherapy in two randomized trials. All patients received four cycles of doxorubicin and cyclophosphamide (AC) followed by three cycles of cyclophosphamide, methotrexate, fluorouracil (CMF). Anemia incidence was related to baseline risk factors. Multivariable analysis used logistic and Cox regression. MAIN RESULTS: Among the 2,215 available patients, anemia was recorded in 11% during adjuvant chemotherapy. Grade 2 and 3 anemia occurred in 4 and 1% of patients, respectively. Pretreatment hemoglobin and white blood cells (WBC) were significant predictors of anemia. Adjusted odds ratios (logistic regression) comparing highest versus lowest quartiles were 0.18 (P < 0.0001) for hemoglobin and 0.52 (P = 0.0045) for WBC. Age, surgery type, platelets, body mass index, and length of time from surgery to chemotherapy were not significant predictors. Cox regression results looking at time to anemia were similar. CONCLUSIONS: Moderate or severe anemia is rare among patients treated with AC followed by CMF. Low baseline hemoglobin and WBC are associated with a higher risk of anemia.

Thrombophilic risk factors in patients with cranial and spinal dural arteriovenous fistulae

OBJECTIVE: Numerous studies have reported the technical aspects and results of surgical and/or endovascular treatment of cranial dural arteriovenous fistulae (cDAVF) and spinal dural arteriovenous fistulae (sDAVF). Only a few of them have addressed the question of thrombophilic conditions, which may be relevant as pathogenetic factors or can increase the risk for venous thromboembolic events. Therefore, the objective of this study is to compare thrombophilic risk factors in patients with cDAVF and sDAVF with no history of trauma. METHODS: A total of 43 patients (25 with cDAVF and 18 with sDAVF) were included in this study. Blood samples were analyzed for G20210A mutation of the prothrombin gene and factor V Leiden mutation. In all patients, prothrombin time, international normalized ratio, fibrinogen, antithrombin, protein C and S activity, von Willebrand factor antigen, ristocetin cofactor activity, D-dimer, coagulation factor VIII activity, and tissue factor pathway inhibitor were determined. Screening was performed for the occurrence of lupus antiphospholipid and cardiolipin antibodies. RESULTS: The prevalence of G20210A mutation of the prothrombin gene was significantly higher in patients with cDAVF (n = 6) compared with patients with sDAVF (n = 0; P < 0.05, Fisher's exact test). A factor V Leiden mutation was found in 3 patients with sDAVF and in 1 patient with cDAVF (P = 0.29, Fisher's exact test). No significant difference was found for other parameters, except for fibrinogen, but decreased protein C activity was more frequent in patients with cDAVF compared with patients with sDAVF (4 versus 1). Decreased protein S activity was encountered in 3 patients (2 with sDAVF and 1 with cDAVF). Cardiolipin antibodies were found in 2 patients with cDAVF but in none with sDAVF, whereas only 1 patient with sDAVF had lupus antiphospholipid antibodies. CONCLUSION: In both groups of patients with dural arteriovenous fistulae, genetic thrombophilic abnormalities occurred in a higher percentage than in the general population. The differences of the genetic abnormalities may be involved in different pathophysiological mechanism(s) in the development of these distinct neurovascular entities.

Are there risk factors in alpine skiing? A controlled multicentre survey of 1278 skiers

OBJECTIVE: To analyse risk factors in alpine skiing. DESIGN: A controlled multicentre survey of injured and non-injured alpine skiers. SETTING: One tertiary and two secondary trauma centres in Bern, Switzerland. PATIENTS AND METHODS: All injured skiers admitted from November 2007 to April 2008 were analysed using a completed questionnaire incorporating 15 parameters. The same questionnaire was distributed to non-injured controls. Multiple logistic regression was performed. Patterns of combined risk factors were calculated by inference trees. A total of 782 patients and 496 controls were interviewed. RESULTS: Parameters that were significant for the patients were: high readiness for risk (p = 0.0365, OR 1.84, 95% CI 1.04 to 3.27); low readiness for speed (p = 0.0008, OR 0.29, 95% CI 0.14 to 0.60); no aggressive behaviour on slopes (p<0.0001, OR 0.19, 95% CI 0.09 to 0.37); new skiing equipment (p = 0.0228, OR 59, 95% CI 0.37 to 0.93); warm-up performed (p = 0.0015, OR 1.79, 95% CI 1.25 to 2.57); old snow compared with fresh snow (p = 0.0155, OR 0.31, 95% CI 0.12 to 0.80); old snow compared with artificial snow (p = 0.0037, OR 0.21, 95% CI 0.07 to 0.60); powder snow compared with slushy snow (p = 0.0035, OR 0.25, 95% CI 0.10 to 0.63); drug consumption (p = 0.0044, OR 5.92, 95% CI 1.74 to 20.11); and alcohol abstinence (p<0.0001, OR 0.14, 95% CI 0.05 to 0.34). Three groups at risk were detected: (1) warm-up 3-12 min, visual analogue scale (VAS)(speed) >4 and bad weather/visibility; (2) VAS(speed) 4-7, icy slopes and not wearing a helmet; (3) warm-up >12 min and new skiing equipment. CONCLUSIONS: Low speed, high readiness for risk, new skiing equipment, old and powder snow, and drug consumption are significant risk factors when skiing. Future work should aim to identify more precisely specific groups at risk and develop recommendations--for example, a snow weather index at valley stations.

Arterial blood pressure during early sepsis and outcome

OBJECTIVE: To evaluate the association between arterial blood pressure (ABP) during the first 24 h and mortality in sepsis. DESIGN: Retrospective cohort study. SETTING: Multidisciplinary intensive care unit (ICU). PATIENTS AND PARTICIPANTS: A total of 274 septic patients. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Hemodynamic, and laboratory parameters were extracted from a PDMS database. The hourly time integral of ABP drops below clinically relevant systolic arterial pressure (SAP), mean arterial pressure (MAP), and mean perfusion pressure (MPP = MAP - central venous pressure) levels was calculated for the first 24 h after ICU admission and compared with 28-day-mortality. Binary and linear regression models (adjusted for SAPS II as a measure of disease severity), and a receiver operating characteristic (ROC) analysis were applied. The areas under the ROC curve were largest for the hourly time integrals of ABP drops below MAP 60 mmHg (0.779 vs. 0.764 for ABP drops below MAP 55 mmHg; P < or = 0.01) and MPP 45 mmHg. No association between the hourly time integrals of ABP drops below certain SAP levels and mortality was detected. One or more episodes of MAP < 60 mmHg increased the risk of death by 2.96 (CI 95%, 1.06-10.36, P = 0.04). The area under the ROC curve to predict the need for renal replacement therapy was highest for the hourly time integral of ABP drops below MAP 75 mmHg. CONCLUSIONS: A MAP level > or = 60 mmHg may be as safe as higher MAP levels during the first 24 h of ICU therapy in septic patients. A higher MAP may be required to maintain kidney function.

Risk factors for treatment-limiting toxicities in patients starting nevirapine-containing antiretroviral therapy

BACKGROUND: This collaboration of seven observational clinical cohorts investigated risk factors for treatment-limiting toxicities in both antiretroviral-naive and experienced patients starting nevirapine-based combination antiretroviral therapy (NVPc). METHODS: Patients starting NVPc after 1 January 1998 were included. CD4 cell count at starting NVPc was classified as high (>400/microl/>250/microl for men/women, respectively) or low. Cox models were used to investigate risk factors for discontinuations due to hypersensitivity reactions (HSR, n = 6547) and discontinuation of NVPc due to treatment-limiting toxicities and/or patient/physician choice (TOXPC, n = 10,186). Patients were classified according to prior antiretroviral treatment experience and CD4 cell count/viral load at start NVPc. Models were stratified by cohort and adjusted for age, sex, nadir CD4 cell count, calendar year of starting NVPc and mode of transmission. RESULTS: Median time from starting NVPc to TOXPC and HSR were 162 days [interquartile range (IQR) 31-737] and 30 days (IQR 17-60), respectively. In adjusted Cox analyses, compared to naive patients with a low CD4 cell count, treatment-experienced patients with high CD4 cell count and viral load more than 400 had a significantly increased risk for HSR [hazard ratio 1.45, confidence interval (CI) 1.03-2.03] and TOXPC within 18 weeks (hazard ratio 1.34, CI 1.08-1.67). In contrast, treatment-experienced patients with high CD4 cell count and viral load less than 400 had no increased risk for HSR 1.10 (0.82-1.46) or TOXPC within 18 weeks (hazard ratio 0.94, CI 0.78-1.13). CONCLUSION: Our results suggest it may be relatively well tolerated to initiate NVPc in antiretroviral-experienced patients with high CD4 cell counts provided there is no detectable viremia.

Prolonged platelet activation in individuals with elevated blood pressure in response to a moderate exercise challenge

We examined the magnitude of 20-min moderate exercise-induced platelet activation in 50 volunteers with normal (n=31) or elevated blood pressure (EBP; n=19). Blood was drawn before, immediately after, and 25 min after exercise. Antibody-staining for platelet activation markers, P-selectin, and fibrinogen receptors was done with and without adenosine diphosphate (ADP) stimulation in whole blood for flow cytometric analyses. Exercise led to increases in percent aggregated platelets and percent platelets expressing P-selectin or PAC-1 binding (ps< or =.001). This increase in percent platelets expressing P-selectin continued even after a 25-min rest only in the EBP group (p< or =.01) accompanied by an increase in percent of aggregated platelets (p< or =.05). Although ADP stimulation led to increased platelet activation at rest, it was attenuated following exercise, even among EBP individuals. A moderate exercise challenge induced prolonged platelet activation in individuals with EBP but attenuation in activation to further stimulation by an agonist. Findings suggest that a recovery period after physical stress appears critical in individuals with high BP regarding platelet activation and aggregation, which can lead to an acute coronary syndrome in vulnerable individuals.

Diseases in neonatal foals. Part 2: potential risk factors for a higher incidence of infectious diseases during the first 30 days post partum

REASON FOR PERFORMING STUDY: The development of clinical illness in foals is usually predetermined by perinatal history, management or stressful environmental conditions. OBJECTIVES: To determine potential risk factors for an increased incidence of infectious diseases during the first 30 days post partum. METHODS: The population consisted of Thoroughbred foals born on stud farms in the Newmarket (UK) area in 2005 (n = 1031). They were followed for their first 30 days. Factors suspected to influence the incidence of infectious neonatal diseases were examined in a logistic regression approach for each of the 3 outcomes (total infectious diseases, systemic disease with diarrhoea and total infectious diseases excluding diarrhoea). All 28 factors were either foal or mare or stud farm related. RESULTS: Several significant risk factors for a higher disease incidence, such as birth complications, colostrum intake by stomach tube and leucocytosis 12-48 h post partum were identified. The factor 'boarding stud' seemed to be protective against disease. CONCLUSION: Some factors, such as the mare's time at stud before foaling, the mare's rotavirus vaccination schedule and fibrinogen-values that empirically had been linked to the outcome previously were not confirmed as relevant. This included the reported useful prophylactic treatment with antimicrobial drugs. POTENTIAL RELEVANCE: Factors to be considered when evaluating newborn foals include: stud management, the birth process, route of colostrum intake, white and red blood cells, and the date of birth. These may help to detect foals at risk to develop an infection so that targeted prophylactic measures can be initiated.

Comparison of arterial blood pressure measurements and hypertension scores obtained by use of three indirect measurement devices in hospitalized dogs

OBJECTIVE: To evaluate the agreement of blood pressure measurements and hypertension scores obtained by use of 3 indirect arterial blood pressure measurement devices in hospitalized dogs. Design-Diagnostic test evaluation. ANIMALS: 29 client-owned dogs. PROCEDURES: 5 to 7 consecutive blood pressure readings were obtained from each dog on each of 3 occasions with a Doppler ultrasonic flow detector, a standard oscillometric device (STO), and a high-definition oscillometric device (HDO). RESULTS: When the individual sets of 5 to 7 readings were evaluated, the coefficient of variation for systolic arterial blood pressure (SAP) exceeded 20% for 0% (Doppler), 11 % (STO), and 28% (HDO) of the sets of readings. After readings that exceeded a 20% coefficient of variation were discarded, repeatability was within 25 (Doppler), 37 (STO), and 39 (HDO) mm Hg for SAP. Correlation of mean values among the devices was between 0.47 and 0.63. Compared with Doppler readings, STO underestimated and HDO overestimated SAP. Limits of agreement between mean readings of any 2 devices were wide. With the hypertension scale used to score SAP, the intraclass correlation of scores was 0.48. Linear-weighted inter-rater reliability between scores was 0.40 (Doppler vs STO), 0.38 (Doppler vs HDO), and 0.29 (STO vs HDO). CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggested that no meaningful clinical comparison can be made between blood pressure readings obtained from the same dog with different indirect blood pressure measurement devices.

Prevalence and risk factors for carriage of multi-drug resistant Staphylococci in healthy cats and dogs

We investigated the distribution of commensal staphylococcal species and determined the prevalence of multi-drug resistance in healthy cats and dogs. Risk factors associated with the carriage of multi-drug resistant strains were explored. Isolates from 256 dogs and 277 cats were identified at the species level using matrix-assisted laser desorption ionisation-time of flight mass spectrometry. The diversity of coagulase-negative Staphylococci (CNS) was high, with 22 species in dogs and 24 in cats. Multi-drug resistance was frequent (17%) and not always associated with the presence of the mecA gene. A stay in a veterinary clinic in the last year was associated with an increased risk of colonisation by multi-drug resistant Staphylococci (OR = 2.4, 95% CI: 1.1˜5.2, p value LRT = 0.04). When identifying efficient control strategies against antibiotic resistance, the presence of mechanisms other than methicillin resistance and the possible role of CNS in the spread of resistance determinants should be considered.

Public health risks of enterobacterial isolates producing extended-spectrum β-lactamases or AmpC β-lactamases in food and food-producing animals: an EU perspective of epidemiology, analytical methods, risk factors, and control options

The blaESBL and blaAmpC genes in Enterobacteriaceae are spread by plasmid-mediated integrons, insertion sequences, and transposons, some of which are homologous in bacteria from food animals, foods, and humans. These genes have been frequently identified in Escherichia coli and Salmonella from food animals, the most common being blaCTX-M-1, blaCTX-M-14, and blaCMY-2. Identification of risk factors for their occurrence in food animals is complex. In addition to generic antimicrobial use, cephalosporin usage is an important risk factor for selection and spread of these genes. Extensive international trade of animals is a further risk factor. There are no data on the effectiveness of individual control options in reducing public health risks. A highly effective option would be to stop or restrict cephalosporin usage in food animals. Decreasing total antimicrobial use is also of high priority. Implementation of measures to limit strain dissemination (increasing farm biosecurity, controls in animal trade, and other general postharvest controls) are also important.

Circadian blood pressure during the early course of type 1 diabetes. Analysis of 1,011 ambulatory blood pressure recordings in 354 adolescents and young adults

OBJECTIVE Little information is available on the early course of hypertension in type 1 diabetes. The aim of our study, therefore, was to document circadian blood pressure profiles in patients with a diabetes duration of up to 20 years and relate daytime and nighttime blood pressure to duration of diabetes, BMI, insulin therapy, and HbA1c. RESEARCH DESIGN AND METHODS Ambulatory profiles of 24-h blood pressure were recorded in 354 pediatric patients with type 1 diabetes (age 14.6 +/- 4.2 years, duration of diabetes 5.6 +/- 5.0 years, follow-up for up to 9 years). A total of 1,011 profiles were available for analysis from patients not receiving antihypertensive medication. RESULTS Although daytime mean systolic pressure was significantly elevated in diabetic subjects (+3.1 mmHg; P < 0.0001), daytime diastolic pressure was not different from from the height- and sex-adjusted normal range (+0.1 mmHg, NS). In contrast, both systolic and diastolic nighttime values were clearly elevated (+7.2 and +4.2 mmHg; P < 0.0001), and nocturnal dipping was reduced (P < 0.0001). Systolic blood pressure was related to overweight in all patients, while diastolic blood pressure was related to metabolic control in young adults. Blood pressure variability was significantly lower in girls compared with boys (P < 0.01). During follow-up, no increase of blood pressure was noted; however, diastolic nocturnal dipping decreased significantly (P < 0.03). Mean daytime blood pressure was significantly related to office blood pressure (r = +0.54 for systolic and r = +0.40 for diastolic pressure); however, hypertension was confirmed by ambulatory blood pressure measurement in only 32% of patients with elevated office blood pressure. CONCLUSIONS During the early course of type 1 diabetes, daytime blood pressure is higher compared with that of healthy control subjects. The elevation of nocturnal values is even more pronounced and nocturnal dipping is reduced. The frequency of white-coat hypertension is high among adolescents with diabetes, and ambulatory blood pressure monitoring avoids unnecessary antihypertensive treatment.

Mice carrying ubiquitin-specific protease 2 (Usp2) gene inactivation maintain normal sodium balance and blood pressure

Ubiquitylation plays an important role in the control of Na⁺ homeostasis by the kidney. It is well established that the epithelial Na⁺ channel ENaC is regulated by the ubiquitin-protein ligase NEDD4-2, limiting ENaC cell surface expression and activity. Ubiquitylation can be reversed by the action of deubiquitylating enzymes (DUBs). One such DUB, USP2-45, was identified previously as an aldosterone-induced protein in the kidney and is also a circadian output gene. In heterologous expression systems, USP2-45 binds to ENaC, deubiquitylates it, and enhances channel density and activity at the cell surface. Because the role of USP2-45 in renal Na⁺ transport had not been studied in vivo, we investigated here the effect of Usp2 gene inactivation in this process. We demonstrate first that USP2-45 protein has a rhythmic expression with a peak at ZT12. Usp2-KO mice did not show any differences from wild-type littermates with respect to the diurnal control of Na⁺ or K⁺ urinary excretion and plasma levels either on a standard diet or after acute and chronic changes to low- and high-Na⁺ diets, respectively. Moreover, they had similar aldosterone levels on either a low- or high-Na⁺ diet. Blood pressure measurements using telemetry did not reveal variations compared with control mice. Usp2-KO mice did not display alterations in expression of genes involved in sodium homeostasis or the ubiquitin system, as evidenced by transcriptome analysis in the kidney. Our data suggest that USP2 does not play a primary role in the control of Na⁺ balance or blood pressure.

Individual risk factors for Mycoplasma hyopneumoniae infections in suckling pigs at the age of weaning.

BACKGROUND In recent years, the occurrence and the relevance of Mycoplasma hyopneumoniae infections in suckling pigs has been examined in several studies. Whereas most of these studies were focused on sole prevalence estimation within different age groups, follow-up of infected piglets or assessment of pathological findings, none of the studies included a detailed analysis of individual and environmental risk factors. Therefore, the aim of the present study was to investigate the frequency of M. hyopneumoniae infections in suckling pigs of endemically infected herds and to identify individual risk factors potentially influencing the infection status of suckling pigs at the age of weaning. RESULTS The animal level prevalence of M. hyopneumoniae infections in suckling pigs examined in three conventional pig breeding herds was 3.6% (41/1127) at the time of weaning. A prevalence of 1.2% was found in the same pigs at the end of their nursery period. In a multivariable Poisson regression model it was found that incidence rate ratios (IRR) for suckling pigs are significantly lower than 1 when teeth grinding was conducted (IRR: 0.10). Moreover, high temperatures in the piglet nest during the first two weeks of life (occasionally >40°C) were associated with a decrease of the probability of an infection (IRR: 0.23-0.40). Contrary, the application of PCV2 vaccines to piglets was associated with an increased infection risk (IRR: 9.72). CONCLUSIONS Since single infected piglets are supposed to act as initiators for the transmission of this pathogen in nursery and fattening pigs, the elimination of the risk factors described in this study should help to reduce the incidence rate of M. hyopneumoniae infections and thereby might contribute to a reduced probability of high prevalences in older pigs.