Blood component ratios in massively transfused, blunt trauma patients--a time-dependent covariate analysis

This study evaluated critical thresholds for fresh frozen plasma (FFP) and platelet (PLT) to packed red blood cell (PRBC) ratios and determined the impact of high FFP:PRBC and PLT:PRBC ratios on outcomes in patients requiring massive transfusion (MT).

Lipid and lipoprotein profile in HIV-infected patients treated with lopinavir/ritonavir as a component of the first combination antiretroviral therapy

We characterized lipid and lipoprotein changes associated with a lopinavir/ritonavir-containing regimen. We enrolled previously antiretroviral-naive patients participating in the Swiss HIV Cohort Study. Fasting blood samples (baseline) were retrieved retrospectively from stored frozen plasma and posttreatment (follow-up) samples were collected prospectively at two separate visits. Lipids and lipoproteins were analyzed at a single reference laboratory. Sixty-five patients had two posttreatment lipid profile measurements and nine had only one. Most of the measured lipids and lipoprotein plasma concentrations increased on lopinavir/ritonavir-based treatment. The percentage of patients with hypertriglyceridemia (TG >150?mg/dl) increased from 28/74 (38%) at baseline to 37/65 (57%) at the second follow-up. We did not find any correlation between lopinavir plasma levels and the concentration of triglycerides. There was weak evidence of an increase in small dense LDL-apoB during the first year of treatment but not beyond 1 year (odds ratio 4.5, 90% CI 0.7 to 29 and 0.9, 90% CI 0.5 to 1.5, respectively). However, 69% of our patients still had undetectable small dense LDL-apoB levels while on treatment. LDL-cholesterol increased by a mean of 17?mg/dl (90% CI -3 to 37) during the first year of treatment, but mean values remained below the cut-off for therapeutic intervention. Despite an increase in the majority of measured lipids and lipoproteins particularly in the first year after initiation, we could not detect an obvious increase of cardiovascular risk resulting from the observed lipid changes.

Demographics of blood pressure and hypertension in children on renal replacement therapy in Europe

Hypertension is a well-known complication in children on renal replacement therapy and an important risk factor for cardiovascular disease in later life. In order to define the prevalence of and risk factors for hypertension among children, we enrolled 3337 pediatric patients from 15 countries in the ESPN/ERA-EDTA Registry of whom 464 were on hemodialysis, 851 on peritoneal dialysis, and 2023 had received a renal allograft. Hypertension was defined as either systolic or diastolic blood pressures in the 95th percentile or greater for age, height, and gender or use of antihypertensive medication. Analyses were adjusted for age, gender, duration, and modality of renal replacement therapy. In 10 countries in which information on the use of antihypertensive medication was available, hypertension was present in over two-thirds of hemodialysis, peritoneal dialysis, or transplant patients. Blood pressure values above the 95th percentile were significantly more prevalent in very young patients (under 3 years) compared to 13- to 17-year olds (odds ratio 2.47), during the first year compared to over 5 years of renal replacement therapy (odds ratio 1.80), and in patients on hemodialysis compared to transplant recipients or those on peritoneal dialysis (odds ratios of 2.48 and 1.59, respectively). Over time, mean blood pressures decreased in both hemodialysis and transplant patients, but not in peritoneal dialysis patients. Hence, our findings highlight the extent of the problem of hypertension in children with end-stage renal disease in Europe.

Sustained acute voltage-dependent blood pressure decrease with prolonged carotid baroreflex activation in therapy-resistant hypertension

Chronic carotid baroreflex stimulation (Rheos system) has been shown to effectively reduce blood pressure in patients with resistant hypertension. Upon acute stimulation blood pressure also falls as a function of voltage. the aim of this study is to evaluate whether this voltage-dependent blood pressure decrease is preserved after long-term carotid baroreflex stimulation.

Use of human embryonic stem cells and umbilical cord blood stem cells for research and therapy: a prospective survey among health care professionals and patients in Switzerland

BACKGROUND: Scientific progress in the biology of hematopoietic stem cells (HSCs) provides opportunities for advances in therapy for different diseases. While stem cell sources such as umbilical cord blood (UCB) are unproblematic, other sources such as human embryonic stem cells (hESCs) raise ethical concerns. STUDY DESIGN AND METHODS: In a prospective survey we established the ethical acceptability of collection, research, and therapy with UCB HSCs versus hESCs among health care professionals, pregnant women, patients undergoing in vitro fertilization therapy, parents, and HSC donors and recipients in Switzerland. RESULTS: There was overall agreement about an ethical justification for the collection of UCB for research and therapy in the majority of participants (82%). In contrast, research and therapy with hESCs was acceptable only by a minority (38% of all responders). The collection of hESCs solely created for HSC collection purposes met overall with the lowest approval rates. Hematologists displayed among the participants the highest acceptance rates for the use of hESCs with 55% for collection, 63% for research, and 73% for therapy. CONCLUSIONS: This is the first study assessing the perception of hESCs for research and therapy in comparison with UCB HSCs in different target groups that are exposed directly, indirectly, or not at all to stem cell-based medicine. Our study shows that the debate over the legitimacy of embryo-destructive transplantation medicine is far from over as particularly hESC research continues to present an ethical problem to an overwhelming majority among laypersons and even among health care professionals.

Effects of microbeam radiation therapy on normal and tumoral blood vessels

Microbeam radiation therapy (MRT) is a new form of preclinical radiotherapy using quasi-parallel arrays of synchrotron X-ray microbeams. While the deposition of several hundred Grays in the microbeam paths, the normal brain tissues presents a high tolerance which is accompanied by the permanence of apparently normal vessels. Conversely, the efficiency of MRT on tumor growth control is thought to be related to a preferential damaging of tumor blood vessels. The high resistance of the healthy vascular network was demonstrated in different animal models by in vivo biphoton microscopy, magnetic resonance imaging, and histological studies. While a transient increase in permeability was shown, the structure of the vessels remained intact. The use of a chick chorioallantoic membrane at different stages of development showed that the damages induced by microbeams depend on vessel maturation. In vivo and ultrastructural observations showed negligible effects of microbeams on the mature vasculature at late stages of development; nevertheless a complete destruction of the immature capillary plexus was found in the microbeam paths. The use of MRT in rodent models revealed a preferential effect on tumor vessels. Although no major modification was observed in the vasculature of normal brain tissue, tumors showed a denudation of capillaries accompanied by transient increased permeability followed by reduced tumor perfusion and finally, a decrease in number of tumor vessels. Thus, MRT is a very promising treatment strategy with pronounced tumor control effects most likely based on the anti-vascular effects of MRT.

Personalized therapy in pain management: where do we stand?

Genomic variations influencing response to pharmacotherapy of pain are currently under investigation. Drug-metabolizing enzymes represent a major target of ongoing research in order to identify associations between an individual's drug response and genetic profile. Polymorphisms of the cytochrome P450 enzymes (CYP2D6) influence metabolism of codeine, tramadol, hydrocodone, oxycodone and tricyclic antidepressants. Blood concentrations of some NSAIDs depend on CYP2C9 and/or CYP2C8 activity. Genomic variants of these genes associate well with NSAIDs' side effect profile. Other candidate genes, such as those encoding (opioid) receptors, transporters and other molecules important for pharmacotherapy in pain management, are discussed; however, study results are often equivocal. Besides genetic variants, further variables, for example, age, disease, comorbidity, concomitant medication, organ function as well as patients' compliance, may have an impact on pharmacotherapy and need to be addressed when pain therapists prescribe medication. Although pharmacogenetics as a diagnostic tool has the potential to improve patient therapy, well-designed studies are needed to demonstrate superiority to conventional dosing regimes.

The relationship between self-efficacy and resting blood pressure in spousal Alzheimer's caregivers

Objective. To examine whether high levels of self-efficacy for problem-focused coping were significantly related to several resting BP measures in spousal Alzheimer's disease caregivers. Design. Cross-sectional. Methods. Participants included 100 older caregivers (mean age = 73.8 ± 8.14 years) providing in home care for a spouse with Alzheimer's disease. All participants completed a 13-item short form of the Coping Self-Efficacy Scale and underwent an in-home assessment where a visiting nurse took the average of three serial BP readings. Multiple regression was used to examine the relationship between self-efficacy and mean arterial pressure (MAP), systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) after controlling for age, gender, smoking history, body mass index, the care recipient's clinical dementia rating, diabetes, alcohol use, and the use of antihypertensive medications. Results. Overall, high levels of self-efficacy for problem-focused coping were associated with lower MAP, SBP, and PP. Self-efficacy for problem-focused coping was marginally associated with resting DBP, but not significant. In addition, we conducted secondary analyses of the other two self-efficacy scales to explore the relationship between each dimension and MAP. We found that there were no significant relationships found between MAP and self-efficacy for stopping unpleasant thoughts/emotions or self-efficacy for getting social support. Conclusions. The present study adds to the current body of literature by illustrating the possibility that higher self-efficacy can have physiological advantages, perhaps by buffering chronic stress's impact on resting BP. Another contribution of the current study is its attempt to understand the role of each individual component of self-efficacy. These findings invite future research to investigate whether caregivers might experience cardiovascular benefits from interventions aimed at enhancing self-efficacy.

3D bloodstain pattern analysis: ballistic reconstruction of the trajectories of blood drops and determination of the centres of origin of the bloodstains

For crime scene investigation in cases of homicide, the pattern of bloodstains at the incident site is of critical importance. The morphology of the bloodstain pattern serves to determine the approximate blood source locations, the minimum number of blows and the positioning of the victim. In the present work, the benefits of the three-dimensional bloodstain pattern analysis, including the ballistic approximation of the trajectories of the blood drops, will be demonstrated using two illustrative cases. The crime scenes were documented in 3D, using the non-contact methods digital photogrammetry, tachymetry and laser scanning. Accurate, true-to-scale 3D models of the crime scenes, including the bloodstain pattern and the traces, were created. For the determination of the areas of origin of the bloodstain pattern, the trajectories of up to 200 well-defined bloodstains were analysed in CAD and photogrammetry software. The ballistic determination of the trajectories was performed using ballistics software. The advantages of this method are the short preparation time on site, the non-contact measurement of the bloodstains and the high accuracy of the bloodstain analysis. It should be expected that this method delivers accurate results regarding the number and position of the areas of origin of bloodstains, in particular the vertical component is determined more precisely than using conventional methods. In both cases relevant forensic conclusions regarding the course of events were enabled by the ballistic bloodstain pattern analysis.

The effect of arts speech therapy on cerebral oxygenation and low frequency hemodynamic oscillations measured using functional near-infrared spectroscopy

Introduction: As a previous study revealed, arts speech therapy (AST) affects cardiorespiratory interaction [1]. The aim of the present study was to investigate whether AST also has effects on brain oxygenation and hemodynamics measured non-invasively using near-infrared spectroscopy (NIRS). Material and methods: NIRS measurements were performed on 17 subjects (8 men and 9 women, mean age: 35.6 ± 12.7 y) during AST. Each measurement lasted 35 min, comprising 8 min pre-baseline, 10 min recitation and 20 min post-baseline. For each subject, measurements were performed for three different AST recitation tasks (recitation of alliterative, hexameter and prose verse). Relative concentration changes of oxyhemoglobin (Δ[O2Hb]) and deoxyhemoglobin (Δ[HHb]) as well as the tissue oxygenation index (TOI) were measured using a Hamamatsu NIRO300 NIRS device and a sensor placed on the subjects forehead. Movement artifacts were removed using a novel method [2]. Statistical analysis (Wilcoxon test) was applied to the data to investigate (i) if the recitation causes changes in the median values and/or in the Mayer wave power spectral density (MW-PSD, range: 0.07–0.13 Hz) of Δ[O2Hb], Δ[HHb] or TOI, and (ii) if these changes vary between the 3 recitation forms. Results: For all three recitation styles a significant (p < 0.05) decrease in Δ[O2Hb] and TOI was found, indicating a decrease in blood flow. These decreases did not vary significantly between the three styles. MW-PSD increased significantly for Δ[O2Hb] when reciting the hexameter and prose verse, and for Δ[HHb] and TOI when reciting alliterations and hexameter, representing an increase in Mayer waves. The MW-PSD increase for Δ[O2Hb] was significantly larger for the hexameter verse compared to alliterative and prose verse Conclusion: The study showed that AST affects brain hemodynamics (oxygenation, blood flow and Mayer waves). Recitation caused a significant decrease in cerebral blood flow for all recitation styles as well as an increase in Mayer waves, particularly for the hexameter, which may indicate a sympathetic activation. References 1. D. Cysarz, D. von Bonin, H. Lackner, P. Heusser, M. Moser, H. Bettermann. Am J Physiol Heart Circ Physiol, 287 (2) (2004), pp. H579–H587 2. F. Scholkmann, S. Spichtig, T. Muehlemann, M. Wolf. Physiol Meas, 31 (5) (2010), pp. 649–662

[Prophylaxis and therapy of postdural puncture headache--a critical evaluation of treatment options]

Since the first description of spinal and epidural anaesthesia, postdural puncture headache (PDPH) is a well known complication. Its prophylaxis and treatment has been studied and discussed for more than 100 years, but the evidence is still limited. Due to relatively low prevalence of PDPH, prospective RCTs are often missing, and the frequently self-limiting character of PDPH impedes an adequate interpretation of results from studies without a control group. Taking side effects and complications into account, a prophylactic treatment of PDPH cannot be recommended. In case of PDPH, non-opioid analgesics are the first choice treatment. The epidural blood patch remains the mainstay of severe PDPH therapy. Noninvasive therapies like theophylline, sumatriptan and ACTH can be an alternative. However, an evidence-based recommendation is lacking. The development of standard operating procedures for accidental dural punctures and PDPH is recommended.

Adverse cardiac events during catecholamine vasopressor therapy: a prospective observational study

PURPOSE: To determine the incidence of and risk factors for adverse cardiac events during catecholamine vasopressor therapy in surgical intensive care unit patients with cardiovascular failure. METHODS: The occurrence of any of seven predefined adverse cardiac events (prolonged elevated heart rate, tachyarrhythmia, myocardial cell damage, acute cardiac arrest or death, pulmonary hypertension-induced right heart dysfunction, reduction of systemic blood flow) was prospectively recorded during catecholamine vasopressor therapy lasting at least 12 h. RESULTS: Fifty-four of 112 study patients developed a total of 114 adverse cardiac events, an incidence of 48.2 % (95 % CI, 38.8-57.6 %). New-onset tachyarrhythmia (49.1 %), prolonged elevated heart rate (23.7 %), and myocardial cell damage (17.5 %) occurred most frequently. Aside from chronic liver diseases, factors independently associated with the occurrence of adverse cardiac events included need for renal replacement therapy, disease severity (assessed by the Simplified Acute Physiology Score II), number of catecholamine vasopressors (OR, 1.73; 95 % CI, 1.08-2.77; p = 0.02) and duration of catecholamine vasopressor therapy (OR, 1.01; 95 % CI, 1-1.01; p = 0.002). Patients developing adverse cardiac events were on catecholamine vasopressors (p < 0.001) and mechanical ventilation (p < 0.001) for longer and had longer intensive care unit stays (p < 0.001) and greater mortality (25.9 vs. 1.7 %; p < 0.001) than patients who did not. CONCLUSIONS: Adverse cardiac events occurred in 48.2 % of surgical intensive care unit patients with cardiovascular failure and were related to morbidity and mortality. The extent and duration of catecholamine vasopressor therapy were independently associated with and may contribute to the pathogenesis of adverse cardiac events.

HIV-1-related Hodgkin lymphoma in the era of combination antiretroviral therapy: incidence and evolution of CD4⁺ T-cell lymphocytes

The risk of Hodgkin lymphoma (HL) is increased in patients infected with HIV-1. We studied the incidence and outcomes of HL, and compared CD4⁺ T-cell trajectories in HL patients and controls matched for duration of combination antiretroviral therapy (cART). A total of 40 168 adult HIV-1-infected patients (median age, 36 years; 70% male; median CD4 cell count, 234 cells/μL) from 16 European cohorts were observed during 159 133 person-years; 78 patients developed HL. The incidence was 49.0 (95% confidence interval [CI], 39.3-61.2) per 100,000 person-years, and similar on cART and not on cART (P = .96). The risk of HL declined as the most recent (time-updated) CD4 count increased: the adjusted hazard ratio comparing more than 350 with less than 50 cells/μL was 0.27 (95% CI, 0.08-0.86). Sixty-one HL cases diagnosed on cART were matched to 1652 controls: during the year before diagnosis, cases lost 98 CD4 cells (95% CI, -159 to -36 cells), whereas controls gained 35 cells (95% CI, 24-46 cells; P < .0001). The incidence of HL is not reduced by cART, and patients whose CD4 cell counts decline despite suppression of HIV-1 replication on cART may harbor HL.