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.

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.

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.

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.

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.

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.

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.

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.

Importance and regulation of the colonic mucus barrier in a mouse model of colitis.

The colonic mucus layer serves as an important barrier and prevents colonic bacteria from invading the mucosa and cause inflammation. The regulation of colonic mucus secretion is poorly understood. The aim of this study was to investigate the role of the mucus barrier in induction of colitis. Furthermore, regulation of mucus secretion by luminal bacterial products was studied. The colon of anesthetized Muc2(-/-), Muc1(-/-), wild-type (wt), and germ-free mice was exteriorized, the mucosal surface was visualized, and mucus thickness was measured with micropipettes. Colitis was induced by DSS (dextran sodium sulfate, 3%, in drinking water), and disease activity index (DAI) was assessed daily. The colonic mucosa of germ-free and conventionally housed mice was exposed to the bacterial products LPS (lipopolysaccharide) and PGN (peptidoglycan). After DSS induction of colitis, the thickness of the firmly adherent mucus layer was significantly thinner after 5 days and onward, which paralleled the increment of DAI. Muc2(-/-) mice, which lacked firmly adherent mucus, were predisposed to colitis, whereas Muc1(-/-) mice were protected with significantly lower DAI by DSS compared with wt mice. The mucus barrier increased in Muc1(-/-) mice in response to DSS, whereas significantly fewer T cells were recruited to the inflamed colon. Mice housed under germ-free conditions had an extremely thin adherent colonic mucus layer, but when exposed to bacterial products (PGN or LPS) the thickness of the adherent mucus layer was quickly restored to levels observed in conventionally housed mice. This study demonstrates a correlation between decreasing mucus barrier and increasing clinical symptoms during onset of colitis. Mice lacking colonic mucus (Muc2(-/-)) were hypersensitive to DSS-induced colitis, whereas Muc1(-/-) were protected, probably through the ability to increase the mucus barrier but also by decreased T cell recruitment to the afflicted site. Furthermore, the ability of bacteria to regulate the thickness of the colonic mucus was demonstrated.

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.

Hyperdense middle cerebral artery sign is an ominous prognostic marker despite optimal workflow.

OBJECTIVES: To evaluate the association between the hyperdense middle cerebral artery sign (HMCAS) and the functional outcome on one hand, and different predictors such as the National Institutes of Health Stroke Scale (NIHSS), infarct size, ASPECTS Score, intracerebral hemorrhage, and mortality on the other hand. MATERIAL AND METHODS: Retrospective analysis of 120 patients with MCA-stroke treated with intravenous thrombolysis. We tested the association between HMCAS and NIHSS, infarct volume, ASPECTS, outcome, level of consciousness, different recorded time intervals, and the day/time of admission. RESULTS: Seventy-four percentage of patients treated with thrombolysis developed cerebral infarction. All patients with HMCAS (n = 39) sustained infarction and only 31% showed favorable outcome compared with 62% and 60%, respectively among patients without HMCAS (P < 0.001 and P = 0.002). There was statistically significant association between functional outcome and HMCAS (P = 0.002), infarct volume, NIHSS, and ASPECTS (P < 0.001). The time to treatment was 12 min shorter in patients who developed infarction (P = 0.037). Independent predictors for outcome were NIHSS and the occurrence of cerebral infarction on computed tomography for the whole study population, and infarct volume for patients who sustained cerebral infarction. CONCLUSIONS: Despite optimal workflow, patients with HMCAS showed poor outcome after intravenous thrombolysis. The results emphasize the urgent need for more effective revascularization therapies and neuroprotective treatment in this subgroup of stroke patients.

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.

Sural nerve biopsy may predict future nerve dysfunction.

OBJECTIVE: Sural nerve pathology in peripheral neuropathy shows correlation with clinical findings and neurophysiological tests. The aim was to investigate progression of nerve dysfunction over time in relation to a baseline nerve biopsy. METHODS: Baseline myelinated nerve fiber density (MNFD) was assessed in sural nerve biopsies from 10 men with type 2 diabetes, 10 with impaired and 10 with normal glucose tolerance. Nerve conduction and quantitative perception thresholds were estimated at baseline and follow-up (7-10 years later). RESULTS: Subjects with low MNFD (< or = 4700 fibers/mm(2)) showed decline of peroneal amplitude (P < 0.02) and conduction velocity (P < 0.04), as well as median nerve sensory amplitude (P < 0.05) and motor conduction velocity (P < 0.04) from baseline to follow-up. In linear regression analyses, diabetes influenced decline of nerve conduction. MNFD correlated negatively with body mass index (r = -0.469; P < 0.02). CONCLUSION: Low MNFD may predict progression of neurophysiological dysfunction and links obesity to myelinated nerve fiber loss.

Fast multiecho balanced SSFP metabolite mapping of (1)H and hyperpolarized (13)C compounds.

OBJECT: To investigate the feasibility of multiecho balanced steady-state free precession (bSSFP)-based fast chemical shift mapping hyperpolarized (13)C metabolites. The overall goal was to reduce total imaging time and to increase spatial resolution compared to common chemical shift imaging (CSI). MATERIALS AND METHODS: A multiecho bSSFP sequence in combination with an iterative reconstruction algorithm was implemented. (1)H experiments were performed on phantoms and on a human volunteer in order to investigate the feasibility of the method on a system with metabolite maps that are known beforehand. (13)C experiments were performed in vivo on pigs, where CSI images were acquired also for comparison. RESULTS: Chemical shift images of three and four distinct (1)H resonance frequencies as well as chemical shift images of up to five hyperpolarized (13)C metabolites were successfully obtained. CONCLUSION: Fast metabolite mapping based on multiecho balanced SSFP in combination with an iterative reconstruction approach could successfully separate several (1)H resonances and hyperpolarized (13)C metabolites.

Risk factors and treatment at recurrent stroke onset: results from the Recurrent Stroke Quality and Epidemiology (RESQUE) Study.

BACKGROUND: Much effort has been made to study first-ever stroke patients. However, recurrent stroke has not been investigated as extensively. It is unclear which risk factors dominate, and whether adequate secondary prevention has been provided to patients who suffer from recurrent stroke. Also, the different types of recurrent stroke need further evaluation. METHODS: The study included patients with recurrent stroke admitted to twenty-three Swedish stroke centers. The type of previous and recurrent stroke was determined, as well as evaluation (when applicable) of recurrent ischemic stroke according to the TOAST classification. Presence of vascular risk factors was registered and compared to the type of stroke. Also assessed was ongoing secondary prevention treatment at recurrent stroke onset. RESULTS: A total of 889 patients with recurrent stroke (mean age 77) were included in the study. Of these, 805 (91%) had ischemic stroke, 78 (9%) had intracerebral hemorrhage and 6 (<1%) stroke of unknown origin. The most frequent vascular risk factors were hypertension (75%) and hyperlipidemia (56%). Among the 889 patients, 29% had atrial fibrillation. Of the patients in the ischemic group with cardiac embolism, only 21% were on anticoagulation treatment. The majority of the patients (75%) had their most recent previous stroke >12 months before admission. CONCLUSIONS: Few patients had a recurrent stroke shortly after the previous stroke in this study. This indicates that it is meaningful to prevent a second event with an adequate long-term treatment strategy for secondary prevention after first-ever stroke. There also seems to be a clear potential for improving secondary prevention after stroke.

Process of foregoing life-sustaining treatment: a survey among Scandinavian intensivists.

BACKGROUND: How ethical issues are dealt with varies considerably depending on the geographic and religious background of individuals. The views of Scandinavian physicians on end-of-life care were studied using a survey. The aim of this study was to clarify the actual processes of foregoing life-sustaining treatment in Scandinavia. METHODS: A questionnaire was developed and sent to 78 intensive care physicians working in Denmark, Finland, Norway and Sweden. RESULTS: Forty-four responses were obtained (13 from Denmark, eight from Finland, 12 from Norway and 11 from Sweden); 89% of the respondents were from University Hospitals. Withholding and withdrawing of treatment were practiced in all intensive care units (ICUs) concerned, but written guidelines on end-of-life care existed in only one ICU. End-of-life care is usually arranged in the ICU. Religious support is available in most hospitals during office hours, but lacking in 26% of ICUs outside office hours. Vasoactive medication, renal replacement therapy, and artificial nutrition are among the therapies most likely to be discontinued during withdrawal of life support. Certain types of monitoring and organ support are still continued in many centers during end-of-life care. CONCLUSION: Local written guidelines on end-of-life care are scarce in Scandinavian ICUs, which may explain the observed variability in the practices. Development of guidelines and monitoring how these instructions are carried out may help to improve the quality of care of dying ICU patients.

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.