Migraine-Associated Common Genetic Variants Confer Greater Risk of Posterior vs. Anterior Circulation Ischemic Stroke☆.

OBJECTIVE: To examine potential genetic relationships between migraine and the two distinct phenotypes posterior circulation ischemic stroke (PCiS) and anterior circulation ischemic stroke (ACiS), we generated migraine polygenic risk scores (PRSs) and compared these between PCiS and ACiS, and separately vs. non-stroke control subjects. METHODS: Acute ischemic stroke cases were classified as PCiS or ACiS based on lesion location on diffusion-weighted MRI. Exclusion criteria were lesions in both vascular territories or uncertain territory; supratentorial PCiS with ipsilateral fetal posterior cerebral artery; and cases with atrial fibrillation. We generated migraine PRS for three migraine phenotypes (any migraine; migraine without aura; migraine with aura) using publicly available GWAS data and compared mean PRSs separately for PCiS and ACiS vs. non-stroke control subjects, and between each stroke phenotype. RESULTS: Our primary analyses included 464 PCiS and 1079 ACiS patients with genetic European ancestry. Compared to non-stroke control subjects (n=15396), PRSs of any migraine were associated with increased risk of PCiS (p=0.01-0.03) and decreased risk of ACiS (p=0.010-0.039). Migraine without aura PRSs were significantly associated with PCiS (p=0.008-0.028), but not with ACiS. When comparing PCiS vs. ACiS directly, migraine PRSs were higher in PCiS vs. ACiS for any migraine (p=0.001-0.010) and migraine without aura (p=0.032-0.048). Migraine with aura PRS did not show a differential association in our analyses. CONCLUSIONS: Our results suggest a stronger genetic overlap between unspecified migraine and migraine without aura with PCiS compared to ACiS. Possible shared mechanisms include dysregulation of cerebral vessel endothelial function.

ClimApp-Integrating Personal Factors with Weather Forecasts for Individualised Warning and Guidance on Thermal Stress.

This paper describes the functional development of the ClimApp tool (available for free on iOS and Android devices), which combines current and 24 h weather forecasting with individual information to offer personalised guidance related to thermal exposure. Heat and cold stress assessments are based on ISO standards and thermal models where environmental settings and personal factors are integrated into the ClimApp index ranging from -4 (extremely cold) to +4 (extremely hot), while a range of -1 and +1 signifies low thermal stress. Advice for individuals or for groups is available, and the user can customise the model input according to their personal situation, including activity level, clothing, body characteristics, heat acclimatisation, indoor or outdoor situation, and geographical location. ClimApp output consists of a weather summary, a brief assessment of the thermal situation, and a thermal stress warning. Advice is provided via infographics and text depending on the user profile. ClimApp is available in 10 languages: English, Danish, Dutch, Swedish, Norwegian, Hellenic (Greek), Italian, German, Spanish and French. The tool also includes a research functionality providing a platform for worker and citizen science projects to collect individual data on physical thermal strain and the experienced thermal strain. The application may therefore improve the translation of heat and cold risk assessments and guidance for subpopulations. ClimApp provides the framework for personalising and downscaling weather reports, alerts and advice at the personal level, based on GPS location and adjustable input of individual factors.

Poor Correlation between Meropenem and Piperacillin Plasma Concentrations and Delivered Dose of Continuous Renal Replacement Therapy.

There is insufficient data on the relationship between antibiotic dosing and plasma concentrations in patients treated with continuous renal replacement therapy (CRRT). In this prospective observational study, we explored the variability in plasma concentrations of meropenem and piperacillin in critically ill patients treated with CRRT and the correlation between concentrations and CRRT intensity. Antibiotic concentrations were measured at the middle and end of the dosing interval and repeated after 2 to 3 days when feasible. Measured concentrations were compared to the clinical susceptible breakpoints for Pseudomonas aeruginosa, 16 and 2 mg/liter for piperacillin and meropenem, respectively. CRRT intensity was estimated by delivered, time-averaged, total effluent flow (Qeff), corrected for predilution. Concentrations were also compared between patients with different residual diuresis. We included 140 meropenem concentrations from 98 patients and 47 piperacillin concentrations from 37 patients. Concentrations at the middle of the dosing interval were above target at all occasions for both antibiotics. For meropenem, 6.5% of trough concentrations were below target, and for piperacillin, 22%. Correlations between Qeff and antibiotic concentrations or the concentration half-life (t1/2) were either statistically not significant or weak. Meropenem concentrations and t1/2 values differed between patients with different residual diuresis. Thus, when treating intensive care patients with CRRT and recommended doses of meropenem or piperacillin, both low, suboptimal plasma concentrations and unnecessarily high, potentially toxic, plasma concentrations are common. Plasma concentrations cannot be predicted from CRRT intensity. Residual diuresis is associated with lower meropenem concentrations, but the correlation is weak. Concentration measurement is probably the most useful approach to avoid suboptimal treatment.

Increasing incidence of colorectal cancer among the younger population in Sweden.

BACKGROUND: The incidence of colorectal cancer in patients aged less than 50 years is increasing in Western countries. This population-based study investigated the age- and sex-specific incidence of colorectal cancer over time in Sweden, and characterized trends in tumour localization and stage at diagnosis. METHODS: Patients diagnosed with colorectal cancer between 1970 and 2016 were identified from the Swedish Cancer Registry, and categorized by sex, age and tumour location. The incidence and average annual percentage change (AAPC) were estimated and compared between age groups. RESULTS: There was an overall increase in the incidence of colorectal cancer between 1970 and 2006, but a decrease in 2006-2016 (AAPC -0·55 (95 per cent c.i. -1·02 to -0·07) per cent). The largest increase in colonic cancer was in 1995-2005 in women aged less than 50 years (AAPC 2·30 (0·09 to 4·56) per cent versus 0·04 (-1·35 to 1·44) and - 0·67 (-1·62 to 0·28) per cent in women aged 50-74 and 75 years or more respectively). Since 1990, rectal cancer increased in patients of both sexes aged below 50 years, with higher AAPC values in women (2006-2016: 2·01 (-1·46 to 5·61) per cent versus 0·20 (-2·25 to 2·71) per cent in men). Younger patients were more likely than those aged 50-74 and 75 years or more to present with stage III-IV colonic (66·2, 57·6 and 49·6 per cent respectively) and rectal (61·2, 54·3 and 51·3 per cent) cancer. From the mid 1990s, rates of proximal and distal colorectal cancer, and rectal cancer were increased in patients aged less than 50 years. CONCLUSION: The overall incidence of colorectal cancer in Sweden decreased in the past decade. However, in patients under 50 years of age the incidence of colorectal cancer - proximal, distal and rectal - continued to increase over time.

ANTECEDENTES: La incidencia del cáncer colorrectal (CCR) en pacientes < 50 años está aumentando en los países occidentales. El objetivo de este estudio de base poblacional fue investigar las tendencias y la incidencia específica por edad y sexo del CCR a lo largo del tiempo en Suecia, así como caracterizar las tendencias en la localización tumoral y en el estadio del CCR en el momento del diagnóstico. MÉTODOS: Los pacientes diagnosticados con CCR entre 1970 y 2016 fueron identificados a partir del Registro de Cáncer de Suecia. Se clasificaron por sexo, edad y localización del tumor. Se calcularon la incidencia media y el promedio del cambio porcentual anual (average annual percentage change, AAPC), comparándose entre los grupos de edad. RESULTADOS: Globalmente, la incidencia de CCR aumentó entre 1970-2006, pero se observó una disminución de 0,6% (i.c. del 95% -1,02 a 0,07) entre 2006-2016. El AAPC del cáncer de colon aumentó con el tiempo tanto en mujeres como en varones. En particular, el mayor aumento se observó entre 1995-2005 en mujeres de < 50 años, que presentaron un AAPC de cáncer de colon de 2,3% (i.c. del 95% 0,09 a 4,56), mayor en comparación con los grupos de edad más avanzada (50-74 años: 0,04%; i.c. del 95% -1,35 a 1,44; grupo de edad 75+: -0,67%; i.c. del 95% -1,62 a 0,28), aunque el análisis de datos proporcionó valores limitados de i.c del 95%. En los varones de < 50 años, el AAPC del cáncer de colon aumentó en un 1,2% (i.c. del 95% -0,80 a 3,21) entre 2006-2016, pero la diferencia no fue significativa en comparación con otros grupos de edad. Desde 1990, los cánceres rectales aumentaron en pacientes de < 50 años, en ambos sexos y en particular en mujeres más que en varones (2006-2016: mujeres 2,0%, i.c. del 95% −1,46 a 5,61 versus varones 0,2%, i.c. del 95% -2,25 a 2,71). En comparación con los grupos de mayor edad, los pacientes de < 50 años tenían más probabilidades de presentar cáncer de colon en estadio III/IV (66%, 58% y 50% en los grupos de edad de < 50, 50-74 y mayores de 75 años, respectivamente) y cáncer de recto (61%, 54% y 51% en los grupos de edad de < 50, 50-74 y mayores de 75 años, respectivamente). Desde mediados de los 90 se observaron tasas cada vez mayores de CCR proximal, distal y de cáncer de recto en pacientes de < 50 años. CONCLUSIÓN: La incidencia global de CCR en Suecia disminuyó en la última década. Sin embargo, en pacientes menores de 50 años, la incidencia del cáncer colorrectal, proximal, distal y rectal ha continuado aumentando a lo largo del tiempo.

Detailed phenotyping of posterior vs. anterior circulation ischemic stroke: a multi-center MRI study.

OBJECTIVE: Posterior circulation ischemic stroke (PCiS) constitutes 20-30% of ischemic stroke cases. Detailed information about differences between PCiS and anterior circulation ischemic stroke (ACiS) remains scarce. Such information might guide clinical decision making and prevention strategies. We studied risk factors and ischemic stroke subtypes in PCiS vs. ACiS and lesion location on magnetic resonance imaging (MRI) in PCiS. METHODS: Out of 3,301 MRIs from 12 sites in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN), we included 2,381 cases with acute DWI lesions. The definition of ACiS or PCiS was based on lesion location. We compared the groups using Chi-squared and logistic regression. RESULTS: PCiS occurred in 718 (30%) patients and ACiS in 1663 (70%). Diabetes and male sex were more common in PCiS vs. ACiS (diabetes 27% vs. 23%, p < 0.05; male sex 68% vs. 58%, p < 0.001). Both were independently associated with PCiS (diabetes, OR = 1.29; 95% CI 1.04-1.61; male sex, OR = 1.46; 95% CI 1.21-1.78). ACiS more commonly had large artery atherosclerosis (25% vs. 20%, p < 0.01) and cardioembolic mechanisms (17% vs. 11%, p < 0.001) compared to PCiS. Small artery occlusion was more common in PCiS vs. ACiS (20% vs. 14%, p < 0.001). Small artery occlusion accounted for 47% of solitary brainstem infarctions. CONCLUSION: Ischemic stroke subtypes differ between the two phenotypes. Diabetes and male sex have a stronger association with PCiS than ACiS. Definitive MRI-based PCiS diagnosis aids etiological investigation and contributes additional insights into specific risk factors and mechanisms of injury in PCiS.

Is carotid imaging underused in patients with transient ischemic attack or ischemic stroke? A Swedish Stroke Register (Riksstroke) study.

BACKGROUND AND AIM: Carotid artery stenosis is one of the major causes of transient ischemic attack (TIA) and acute ischemic stroke (IS), and carotid surgery and stenting are used to reduce the risk of ipsilateral IS. However, the adherence to the recommendation of carotid imaging in clinical practice has not been well studied. We analyzed proportions of carotid imaging and determinants for its non-use in patients with TIA and IS with respect to baseline demographics, risk factors, hospital characteristics, and geographical region. PATIENTS AND METHODS: Hospital-based data on TIA and IS events, registered from July 2011 to June 2013, were obtained from the Swedish Stroke Register (Riksstroke). Carotid imaging diagnostics included carotid Doppler ultrasound and computed tomography angiography. RESULTS: Carotid imaging was performed in 70% (10 545/15 021) of patients with TIA and 54% (23 772/44 075) of patients with IS. The most significant independent determinants for not undergoing carotid imaging were, in patients with TIA: age ≥85 year (odds ratio (OR), 7.3; 95% confidence interval (CI), 6.4-8.4) and a history of stroke (OR, 2.3; 95% CI, 2.1-2.5); and in patients with IS: age ≥85 year (OR, 9.8; 95% CI, 9.0-10.6), age 75-84 year (OR, 2.5; 95% CI, 2.3-2.7), and reduced level of consciousness at admission (OR, 3.4; 95% CI, 3.1-3.6). Care at a University hospital and in a stroke unit increased the likelihood of carotid imaging. There were substantial regional variations regarding proportions of carotid imaging. CONCLUSION: Carotid imaging appears to be underused in patients with TIA and IS. Opportunities of secondary stroke prevention with carotid interventions are likely missed.

Transient ischemic attack and ischemic stroke patients with or without prior stroke.

OBJECTIVES: A history of stroke is common in patients with transient ischemic attack (TIA) and ischemic stroke (IS), but there are few reports characterizing this group of patients. We aimed to compare characteristics, risk factors, and secondary preventive treatment in patients with TIA or IS with vs without a history of stroke. METHODS: Hospital-based data on TIA and IS events, registered from July 2011 to June 2013, were obtained from the Swedish Stroke Register (Riksstroke). Previous stroke was not specified as hemorrhagic or ischemic. RESULTS: A history of stroke was present in 19.3% (2892/15012) of TIA and 24.6% (10853/44169) of IS patients. Patients with prior stroke were older, more often male, and more likely to have atrial fibrillation (AF) (TIA: 27.4% vs 16.4%; IS: 36.1% vs 28.0%), hypertension (TIA: 77.5% vs 56.4%; IS: 74.2% vs 59.0%), and diabetes mellitus (TIA: 22.2% vs 14.2%; IS: 26.3% vs 19.5%) compared with those without (all differences P<.0001). At discharge, patients with prior stroke were more often treated with antihypertensive drugs than those without, whereas proportions treated with statins were similar in both groups. Patients with AF and prior stroke were less often treated with oral anticoagulant (OAC) medication than those without prior stroke. CONCLUSIONS: Both in TIA and IS, vascular risk factors were more common in patients with a history of stroke compared with those without. In contrast to other secondary preventive medications, OAC treatment in the presence of AF was underutilized in patients with a history of stroke.

The influence of gravity on regional lung blood flow in humans: SPECT in the upright and head-down posture.

Previous studies in humans have shown that gravity has little influence on the distribution of lung blood flow while changing posture from supine to prone. This study aimed to evaluate the maximal influence of posture by comparison of regional lung blood flow in the upright and head-down posture in 8 healthy volunteers, using a tilt table. Regional lung blood flow was marked by intravenous injection of macroaggregates of human albumin labeled with 99mTc or 113mIn, in the upright and head-down posture, respectively, during tidal breathing. Both radiotracers remain fixed in the lung after administration. The distribution of radioactivity was mapped using quantitative single photon emission computed tomography (SPECT) corrected for attenuation and scatter. All images were obtained supine during tidal breathing. A shift from upright to the head-down posture caused a clear redistribution of blood flow from basal to apical regions. We conclude that posture plays a role for the distribution of lung blood flow in upright humans, and that the influence of posture, and thereby gravity, is much greater in the upright and head-down posture than in horizontal postures. However, the results of the study demonstrate that lung structure is the main determinant of regional blood flow and gravity is a secondary contributor to the distribution of lung blood flow in the upright and head-down positions.NEW & NOTEWORTHY Using a dual-isotope quantitative SPECT method, we demonstrated that although a shift in posture redistributes blood flow in the direction of gravity, the results are also consistent with lung structure being a greater determinant of regional blood flow than gravity. To our knowledge, this is the first study to use modern imaging methods to quantify the shift in regional lung blood flow in humans at a change between the upright and head-down postures.

Standard dosing of piperacillin and meropenem fail to achieve adequate plasma concentrations in ICU patients.

BACKGROUND: Controversies remain regarding optimal dosing and the need for plasma concentration measurements when treating intensive care patients with beta-lactam antibiotics. METHODS: We studied ICU patients treated with either antibiotic, excluding patients on renal replacement therapy. Antibiotic concentrations were measured at the mid and end of the dosing interval, and repeated after 2-3 days when feasible. Glomerular filtration rate (GFR) was estimated from plasma creatinine and cystatin C, GFR calculated from cystatin C (eGFR) and measured creatinine clearance (CrCl). Measured concentrations were compared to the clinical susceptible breakpoints for Pseudomonas aeruginosa, 16 and 2 mg/l for piperacillin and meropenem respectively. RESULTS: We analysed 33 and 31 paired samples from 20 and 19 patients treated with piperacillin-tazobactam and meropenem respectively. Antibiotic concentrations at the mid and end of the dosing interval were for piperacillin, 27.0 (14.7-52.9) and 8.6 (2.7-30.3); and for meropenem, 7.5 (4.7-10.2) and 2.4 (1.0-3.5). All values median (interquartile range) and concentrations in mg/l. The percentage of measured concentrations below the breakpoint at the mid and end of the dosing interval were for piperacillin, 27% and 61%; and for meropenem, 6% and 48%. Lower estimates of GFR were associated with higher concentrations but concentrations varied greatly between patients with similar GFR. The correlation with terminal concentration half-life was similar for eGFR and CrCl. CONCLUSIONS: With standard doses of meropenem and piperacillin-tazobactam, plasma concentrations in ICU patients vary > 10-fold and are suboptimal in a significant percentage of patients. The variation is large also between patients with similar renal function.

European Stroke Organisation (ESO) guidelines for the management of temperature in patients with acute ischemic stroke

BACKGROUND: Hyperthermia is a frequent complication in patients with acute ischemic stroke. On the other hand, therapeutically induced hypothermia has shown promising potential in animal models of focal cerebral ischemia. This Guideline Document presents the European Stroke Organisation guidelines for the management of temperature in patients with acute ischemic stroke. METHODS: A multidisciplinary group identified related questions and developed its recommendations based on evidence from randomized controlled trials elaborating the Grading of Recommendations Assessment, Development, and Evaluation approach. This Guideline Document was reviewed within the European Stroke Organisation and externally and was approved by the European Stroke Organisation Guidelines Committee and the European Stroke Organisation Executive Committee. RESULTS: We found low-quality evidence, and therefore, we cannot make any recommendation for treating hyperthermia as a means to improve functional outcome and/or survival in patients with acute ischemic stroke and hyperthermia; moderate evidence to suggest against routine prevention of hyperthermia with antipyretics as a means to improve functional outcome and/or survival in patients with acute ischemic stroke and normothermia; very low-quality evidence to suggest against routine induction of hypothermia as a means to improve functional outcome and/or survival in patients with acute ischemic stroke. CONCLUSIONS: The currently available data about the management of temperature in patients with acute ischemic stroke are limited, and the strengths of the recommendations are therefore weak. We call for new randomized controlled trials as well as recruitment of eligible patients to ongoing randomized controlled trials to allow for better-informed recommendations in the future.(AU)

European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage

"BACKGROUND: Intracerebral hemorrhage (ICH) accounted for 9% to 27% of all strokes worldwide in the last decade, with high early case fatality and poor functional outcome. In view of recent randomized controlled trials (RCTs) of the management of ICH, the European Stroke Organisation (ESO) has updated its evidence-based guidelines for the management of ICH. METHOD: A multidisciplinary writing committee of 24 researchers from 11 European countries identified 20 questions relating to ICH management and created recommendations based on the evidence in RCTs using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: We found moderate- to high-quality evidence to support strong recommendations for managing patients with acute ICH on an acute stroke unit, avoiding hemostatic therapy for acute ICH not associated with antithrombotic drug use, avoiding graduated compression stockings, using intermittent pneumatic compression in immobile patients, and using blood pressure lowering for secondary prevention. We found moderate-quality evidence to support weak recommendations for intensive lowering of systolic blood pressure to <140 mmHg within six-hours of ICH onset, early surgery for patients with a Glasgow Coma Scale score 9-12, and avoidance of corticosteroids. CONCLUSION: These guidelines inform the management of ICH based on evidence for the effects of treatments in RCTs. Outcome after ICH remains poor, prioritizing further RCTs of interventions to improve outcome."

Escalation to weekly dosing recaptures response in adalimumab-treated patients with moderately to severely active ulcerative colitis.

BACKGROUND: Patients with moderately to severely active ulcerative colitis occasionally do not respond to or lose initial response to maintenance dosing of anti-TNF therapy. AIM: To report the efficacy of escalation from every other week (EOW) to weekly adalimumab dosing in patients from the clinical trial ULTRA 2 (NCT00408629), by week 8 response (i.e. response after adalimumab induction therapy). METHODS: Week 52 remission, response, and mucosal healing rates were assessed in ULTRA 2 adalimumab-randomised patients who escalated to weekly dosing. Patients were stratified by week 8 response per partial Mayo score. Kaplan-Meier and logistic regression analyses estimated time to weekly dosing and defined predictors of escalation to weekly dosing, respectively. Adverse events were reported for patients receiving open-label adalimumab. RESULTS: The rate of escalation to weekly dosing was 16.3% (20/123) for week 8 responders and 38.4% (48/125) for week 8 nonresponders. Week 52 remission, response and mucosal healing rates with weekly dosing were 20%, 45%, and 45% for week 8 responders and 2.1%, 25% and 29.2% for nonresponders, respectively (NRI). The median time to weekly dosing was 288 days for week 8 nonresponders and not estimable for responders. Prior anti-TNF use was a significant predictor of escalation to weekly dosing. Treatment-emergent adverse event rates were similar for patients receiving open-label EOW or weekly adalimumab. CONCLUSIONS: Escalation to weekly adalimumab dosing demonstrated clinical benefits for patients who lost response to therapy and may be beneficial for patients not initially responding to induction therapy. No new safety risks were identified with weekly dosing.

Time course analysis of mechanical ventilation-induced diaphragm contractile muscle dysfunction in the rat.

Controlled mechanical ventilation (CMV) plays a key role in triggering the impaired diaphragm muscle function and the concomitant delayed weaning from the respirator in critically ill intensive care unit (ICU) patients. To date, experimental and clinical studies have primarily focused on early effects on the diaphragm by CMV, or at specific time points. To improve our understanding of the mechanisms underlying the impaired diaphragm muscle function in response to mechanical ventilation, we have performed time-resolved analyses between 6 h and 14 days using an experimental rat ICU model allowing detailed studies of the diaphragm in response to long-term CMV. A rapid and early decline in maximum muscle fibre force and preceding muscle fibre atrophy was observed in the diaphragm in response to CMV, resulting in an 85% reduction in residual diaphragm fibre function after 9-14 days of CMV. A modest loss of contractile proteins was observed and linked to an early activation of the ubiquitin proteasome pathway, myosin:actin ratios were not affected and the transcriptional regulation of myosin isoforms did not show any dramatic changes during the observation period. Furthermore, small angle X-ray diffraction analyses demonstrate that myosin can bind to actin in an ATP-dependent manner even after 9-14 days of exposure to CMV. Thus, quantitative changes in muscle fibre size and contractile proteins are not the dominating factors underlying the dramatic decline in diaphragm muscle function in response to CMV, in contrast to earlier observations in limb muscles. The observed early loss of subsarcolemmal neuronal nitric oxide synthase activity, onset of oxidative stress, intracellular lipid accumulation and post-translational protein modifications strongly argue for significant qualitative changes in contractile proteins causing the severely impaired residual function in diaphragm fibres after long-term mechanical ventilation. For the first time, the present study demonstrates novel changes in the diaphragm structure/function and underlying mechanisms at the gene, protein and cellular levels in response to CMV at a high temporal resolution ranging from 6 h to 14 days.

Regional lung ventilation in humans during hypergravity studied with quantitative SPECT.

Recently we challenged the view that arterial desaturation during hypergravity is caused by redistribution of blood flow to dependent lung regions by demonstrating a paradoxical redistribution of blood flow towards non-dependent regions. We have now quantified regional ventilation in 10 healthy supine volunteers at normal and three times normal gravity (1G and 3G). Regional ventilation was measured with Technegas ((99m)Tc) and quantitative single photon emission computed tomography (SPECT). Hypergravity caused arterial desaturation, mean decrease 8%, p<0.05 vs. 1G. The ratio for mean ventilation per voxel for non-dependent and dependent lung regions was 0.81±0.12 during 1G and 1.63±0.35 during 3G (mean±SD), p<0.0001. Thus, regional ventilation was shifted from dependent to non-dependent regions. We suggest that arterial desaturation during hypergravity is caused by quantitatively different redistributions of blood flow and ventilation. To our knowledge, this is the first study presenting high-resolution measurements of regional ventilation in humans breathing normally during hypergravity.

High incidence of post-injury pneumonia in intensive care-treated trauma patients.

INTRODUCTION: Trauma patients are susceptible to post-injury infections. We investigated the incidence, as well as risk factors for development of pneumonia in intensive care unit (ICU)-treated trauma patients. In addition, we report pathogens identified in patients that developed pneumonia. METHODS: The study cohort consisted of 322 trauma patients admitted to the ICU at a level-one trauma centre following initial resuscitation. Patients 15 years or older with an ICU stay of more than 24 h were included. We investigated pre-hospital and hospital parameters during the first 24 h after admission and their possible association with pneumonia within 10 days of ICU admission. RESULTS: Majority of the patients were male (78%) and the median age was 41 years. The overall degree of injury was high with a median Injury Severity Score (ISS) of 24. Overall 30-day mortality was 9%. Eighty-five (26%) patients developed pneumonia during their first 10 days in the ICU. Univariate logistic regression revealed that intubation in the field, shock, Glasgow Coma Scale (GCS) 3-8, major surgery within 24 h after admission, massive transfusion and ISS > 24 were all risk factors for subsequent development of pneumonia. In the multivariable model, only GCS 3-8 was identified as an independent risk factor. In 42 out of the 85 cases of pneumonia, the diagnosis was defined by significant growth of at least one pathogen where Enterobacteriaceae and Staphylococcus aureus were the most common. CONCLUSIONS: Pneumonia is a common complication among ICU-treated trauma patients. Reduced consciousness is an independent risk factor for development of pneumonia after severe injury.

Feasibility of endovascular and surface cooling strategies in acute stroke.

BACKGROUND: Therapeutic hypothermia (TH) is a promising treatment of stroke, but limited data are available regarding the safety and effectiveness of cooling methodology. We investigated the safety of TH and compared the cooling capacity of two widely used cooling strategies - endovascular and surface cooling. METHODS: COOLAID Oresund is a bicentre randomized trial in Copenhagen (Denmark) and Malmö (Sweden). Patients were randomized to either TH (33°C for 24 h) in a general intensive care unit (ICU) or standardized stroke unit care (control). Cooling was induced by a surface or endovascular-based strategy. RESULTS: Thirty-one patients were randomized. Seven were cooled using endovascular and 10 using surface-based cooling methods and 14 patients received standard care (controls). 14 (45%) patients received thrombolysis. Pneumonia was recorded in 6 (35%) TH patients and in 1 (7%) control. 4 TH patients and 1 control developed massive infarction. 1 TH patient and 2 control suffered asymptomatic haemorrhagic transformation. Mortality was comparable with 2 (12%) in the TH group and 1 (7%) among controls. Mean (SD) duration of hospital stay was 25.0 days (24, 9) in TH and 22.5 days (20.6) in control patients (P = 0.767). Mean (SD) induction period (cooling onset to target temperature) was 126.3 min (80.6) with endovascular cooling and 196.3 min (76.3) with surface cooling (P = 0.025). CONCLUSIONS: Therapeutic hypothermia with general anaesthesia is feasible in stroke patients. We noticed increased rates of pneumonia, while the length of hospital stay remained comparable. The endovascular cooling strategy provides a faster induction period than surface cooling.

Fast metabolite mapping in the pig heart after injection of hyperpolarized 13C-pyruvate with low-flip angle balanced steady-state free precession imaging.

The conversion of hyperpolarized (13)C pyruvate to metabolic products in the Krebs cycle provides valuable information about the metabolic status and the viability of the myocardium. Therefore, imaging methods must be able to spectrally discriminate different (13)C metabolites. However, the requirement for spectral selectivity conflicts with the demands for rapid image acquisition and high spatial resolution in cardiac imaging. In this work, the feasibility of a balanced steady state free precession sequence with low flip angles was investigated in the pig heart after injection of hyperpolarized (13)C(1)-pyruvate. Using cardiac gating, it was possible to acquire (13)C-bicarbonate images within a single heartbeat (acquisition time 150 ms) without destroying the substrate signal from the hyperpolarized pyruvate. Therefore, the technique may be useful in dynamic studies of cardiac metabolism.

Hyperpolarized molecules in solution.

Hyperpolarization is a technique to enhance the nuclear polarization and thereby increase the available signal in magnetic resonance (MR). This chapter provides an introduction to the concept of hyperpolarization as well as an overview of dynamic nuclear polarization (DNP) and para-hydrogen induced polarization (PHIP), two methods used to generate hyperpolarized molecules in aqueous solution.

Applications of hyperpolarized agents in solutions.

This chapter provides an overview of pulse sequences adapted to hyperpolarized MR imaging. Applications of hyperpolarized agents in aqueous solution are reviewed. Vascular (e.g., angiography, perfusion, and catheter tracking) as well as metabolic (e.g., oncology, cardiology, neurology, and pH mapping) applications are covered. Due to the rapid development of new applications for hyperpolarized agents, a review format has been used for this chapter instead of a strict protocol/procedure structure.