Multivariable Analysis of Pre-operative Brain Atrophy as a Predictor of Long Term Mortality After Carotid Endarterectomy.

OBJECTIVE: Brain atrophy is associated with an increased mortality rate in elderly trauma patients and in patients treated with mechanical thrombectomy for acute ischaemic stroke. In the setting of ischaemic stroke, the association between brain atrophy and death is stronger than that of sarcopenia. It has previously been shown that lower masseter area, as a marker of sarcopenia, is linked to lower survival after carotid endarterectomy (CEA). The aim of this study was to investigate whether brain atrophy is also associated with long term mortality in patients undergoing CEA. METHODS: A cohort of patients treated with CEA between 2004 and 2010 was retrieved from the Tampere University Hospital vascular registry and those with available pre-operative computed tomography (CT) imaging were analysed retrospectively. CT images were evaluated for brain atrophy index (BAI) and masseter muscle surface area and density. The association between BAI and mortality was investigated with Cox regression. RESULTS: Two hundred and thirty-three patients with a median (interquartile range [IQR]) age of 71 years (64.0, 77.0) were included. Most patients were operated on for symptomatic stenosis (n = 203; 87.1%). The median (IQR) duration of follow up was 115.0 months (66.0, 153.0), and 155 patients (66.5%) died during follow up. BAI was statistically significantly correlated with age (r = .489), average masseter density (r = -.202), and smoking (r = -.186; all p <.005). Increased BAI was statistically significantly associated with overall mortality (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.25 - 1.68, per one standard deviation [SD] increase) in the univariable analysis, and the association remained (HR 1.23, 95% CI 1.04 - 1.46, per one SD increase) in the multivariable models. Age, peripheral artery disease, and chronic obstructive pulmonary disease were also independently associated with mortality. The optimal cutoff value for BAI was 0.133. CONCLUSION: Brain atrophy independently predicts the long term post-operative mortality rate after CEA in a cohort containing mainly symptomatic patients. Future studies are needed to validate the results in prospective settings and in asymptomatic patients.

Pre-Operative Masseter Area is an Independent Predictor of Long-Term Survival after Carotid Endarterectomy.

OBJECTIVE/BACKGROUND: Sarcopenia is a predictor of mortality in elderly patients. Masseter area (MA) reflects sarcopenia in trauma patients. It was hypothesised that MA and Masseter density (MD) could be evaluated reliably from pre-operative computed tomography angiography (CTA) scans and that they predict post-operative survival in carotid endarterectomy (CEA) patients. METHODS: This was an observational registry study. Patients (n = 242) were operated on for asymptomatic stenosis (n = 32; 13.2%), amaurosis fugax (n = 41; 16.9%), transient ischaemic attack (n = 85; 35.1%), or ischaemic stroke (n = 84; 34.7%). Internal carotid artery stenoses were graded angiographically. Intraclass correlation coefficient (ICC) was used to analyse measurement reliability by three independent observers. Cox regression analysis was used to study the effect of MA and MD on survival (hazard ratio [HR]). RESULTS: Median patient age was 71.0 years (interquartile range [IQR] 13.0) and follow up time was 68.5 months (range 3-163 months); at the end of follow up (1 October 2017), 104 (43.0%) patients had died according to the National Population Register. The average MA (MAavg, the mean of left and right MA [median 394.0 mm2; IQR 110.1 mm2]) and MD (MDavg, the mean of left and right MD [median 53.5 HU; IQR 16.5 HU]) could be measured with excellent reliability (ICC > 0.865, p < .001 for all). In multivariable analyses only body surface area (BSA) (p < .001) and dental status were associated with MAavg (p = .021). Increased MAavg predicted lower mortality (HR 0.76, 95% confidence interval [CI] 0.61-0.96; p = .023) independent of age (HR 1.05, 95% CI 1.02-1.07; p = 0.001), female sex, body mass index, renal insufficiency, ipsilateral stenosis, indication category, and presence of teeth. MDavg was not associated with mortality. After further adjustment, BSA (the most significant determinant of MAavg) did not alter the association between MAavg and mortality (0.75, 95% CI 0.58-0.97; p = .031). CONCLUSION: Average MA but not MD measured from the pre-operative CTA scan provides a reliable estimate of post-operative long-term survival in CEA patients independent of other risk factors, anthropometric measurements, and dental status.

Electronic Nose in the Detection of Wound Infection Bacteria from Bacterial Cultures: A Proof-of-Principle Study.

BACKGROUND: Soft tissue infections, including postoperative wound infections, result in a significant burden for modern society. Rapid diagnosis of wound infections is based on bacterial stains, cultures, and polymerase chain reaction assays, and the results are available earliest after several hours, but more often not until days after. Therefore, antibiotic treatment is often administered empirically without a specific diagnosis. METHODS: We employed our electronic nose (eNose) system for this proof-of-concept study, aiming to differentiate the most relevant bacteria causing wound infections utilizing a set of clinical bacterial cultures on identical blood culture dishes, and established bacterial lines from the gaseous headspace. RESULTS: Our eNose system was capable of differentiating both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa, and Clostridium perfringens with an accuracy of 78% within minutes without prior sample preparation. Most importantly, the system was capable of differentiating MRSA from MSSA with a sensitivity of 83%, a specificity of 100%, and an overall accuracy of 91%. CONCLUSIONS: Our results support the concept of rapid detection of the most relevant bacteria causing wound infections and ultimately differentiating MRSA from MSSA utilizing gaseous headspace sampling with an eNose.

Chronic Kidney Diseases Among Patients Undergoing Elective Arthroplasty: Risk Groups and the Value of Serum Creatinine.

BACKGROUND: In arthroplasty clinics, we tend to evaluate patient's kidney function looking at serum creatinine (SCr), while estimated glomerular filtration rate (eGFR) is recommended. We reported the prevalence of chronic kidney disease (CKD; eGFR <60 mL/min/1.73 m2) in different patient groups and investigated whether CKD is missed by evaluation based on SCr. METHODS: Preoperative SCr values were used to calculate eGFR in 20,575 consecutive hip or knee arthroplasties. RESULTS: Prevalence of CKD was 9%-12%. It was higher among older women, knee arthroplasty patients, and patients with hypertension, diabetes, or coronary disease. Using SCr instead of eGFR leads to missing CKD in up to 7% of the cases. In older women and older patients with body mass index <25 kg/m2, half of CKD cases were missed. CONCLUSION: Use of eGFR instead of SCr to detect CKD more accurately is recommended.

The Finnish Prehospital Stroke Scale Detects Thrombectomy and Thrombolysis Candidates-A Propensity Score-Matched Study.

BACKGROUND: Prehospital stroke triage is challenged by endovascular treatment for large vessel occlusion (LVO) being available only in major stroke centers. Conjugate eye deviation (CED) is closely related to LVO, whereas common stroke signs (face-arm-leg-speech-visual) screen stroke. We hypothesized that combining CED with common stroke signs would yield a prehospital stroke scale for identifying both LVO and stroke in general. METHODS AND RESULTS: We retrospectively analyzed consecutive patients (n = 856) with prehospital Code Stroke (recanalization candidate). The National Institutes of Health Stroke Scale (NIHSS) and computed tomography were administered to patients on arrival. Computed tomography angiography was performed on patients with NIHSS score of 8 or greater and considered to benefit from endovascular treatment. With random forest analysis and deviance analysis of the general linear model we confirmed the superiority of the NIHSS "Best Gaze" over other NIHSS items in detecting LVO. Based on this and commonly used stroke signs we presented the Finnish Prehospital Stroke Scale (FPSS) including dichotomized face drooping, extremity weakness, speech difficulty, visual disturbance, and CED. FPSS detected LVO with a sensitivity of 54%, specificity of 91%, positive predictive value of 48%, negative predictive value of 93%, and likelihood ratio of 6.2. CONCLUSIONS: Based on CED and universally used stroke signs, FPSS recognizes stroke in general and additionally, LVO as a stroke subtype comparably to other scales intended to detect LVO only. As the FPSS items are dichotomized, it is likely to be easy for emergency medical services to implement.

Urinary Polyamines as Biomarkers for Ovarian Cancer.

OBJECTIVES: Elevated concentrations of polyamines have been found in urine of patients with malignant tumors, including ovarian cancer. Previous research has suffered from poorly standardized detection methods. Our liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is capable of simultaneous standardized analysis of most known polyamines. Liquid chromatography-tandem mass spectrometry has not previously been used in the differential diagnostics of ovarian tumors in postmenopausal women. MATERIALS AND METHODS: In this prospective study, postmenopausal women (n = 71) presenting with an adnexal mass and, as controls, women with genital prolapse or urinary incontinence scheduled for surgery (n = 22) were recruited in the study. For analysis of the polyamines, a morning urine sample was obtained before surgery. Preoperative serum CA125 concentrations were determined in the study group. RESULTS: Twenty-three women with benign and 37 with malignant ovarian tumors were eligible. Of all analyzed polyamines, only urinary N,N-diacetylspermine showed statistically significant differences between all groups except controls versus benign tumors. N,N-diacetylspermine was elevated in malignant versus benign tumors (P < 0.001), in high-grade versus low malignant potential tumors (P < 0.001), in stage III to IV versus stage I to II cancers (P < 0.001), and even in early-stage cancer (stage I-II) versus benign tumors (P = 0.017). N,N-diacetylspermine had better sensitivity (86.5%) but lower specificity (65.2%) for distinguishing benign and malignant ovarian tumors than CA125 with a cut-off value of 35 kU/L (sensitivity, 75.7%; specificity, 69.6%). CONCLUSIONS: Urinary N,N-diacetylspermine seems to be able to distinguish benign and malignant ovarian tumors as well as early and advanced stage, and low malignant potential and high-grade ovarian cancers from each other, respectively.

White matter lesions are associated with hospital admissions because of hip-fractures and trauma after ischemic stroke.

BACKGROUND AND PURPOSE: Cerebral white matter lesions (WMLs), a surrogate for cerebral small-vessel disease, have been shown to be associated with decreasing mobility, gait instability, and falls. The aim of this study was to investigate whether WMLs of the brain are associated with increased incidence of hospital admissions because of any trauma and hip-fractures in a cohort of patients with stroke. METHODS: We included 383 consecutive patients aged 55 to 85 years with ischemic stroke admitted to the Helsinki University Central Hospital (The Stroke Aging Memory cohort) with a 12-year follow-up. National register data were reviewed for hip-fractures, other traumatic injuries, survival data, and causes of death. WMLs were rated using MRI and dichotomized as none to mild and moderate to severe. The data were analyzed using Kaplan-Meier plots (log-rank) and a complex Cox multivariable hazards models for multiple cases per subject to assess hazard ratios with their 95% confidence intervals. RESULTS: During the 12-year follow-up, there were more hip-fractures (13.5% versus 6.5%; log-rank, P=0.01) and more hospital admissions because of traumatic injury (22.2% versus 16.7%; log-rank, P=0.04) in the moderate-to-severe than in the none-to-mild WMLs group. In the complex samples, Cox multivariable model adjusting for age, sex, National Institutes of Health Stroke Scale, infarct size, and poststroke dementia, moderate-to-severe WMLs were associated with increased incidences of hospital admissions because of hip-fractures (hazard ratio, 3.98; 95% confidence interval, 1.55-10.21) and traumatic injuries including hip-fractures (hazard ratio, 1.72; 95% confidence interval, 1.03-2.87). CONCLUSIONS: Patients with ischemic stroke and moderate-to-severe WMLs are at high risk, who experience serious traumatic injuries and especially hip-fractures requiring hospital treatment.

Detection of prostate cancer by an electronic nose: a proof of principle study.

PURPOSE: We evaluate the ability of an electronic nose to discriminate prostate cancer from benign prostatic hyperplasia using urine headspace, potentially offering a clinically applicable noninvasive and rapid diagnostic method. MATERIALS AND METHODS: The ChemPro® 100-eNose was used to discriminate prostate cancer from benign prostatic hyperplasia using urine sample headspace. Its performance was tested with 50 patients with confirmed prostate cancer and 24 samples from 15 patients with benign prostatic hyperplasia (15 patients provided urine preoperatively and 9 patients provided samples 3 months postoperatively) scheduled to undergo robotic assisted laparoscopic radical prostatectomy or transurethral resection of prostate, respectively. The patients provided urine sample preoperatively and those with benign prostatic hyperplasia also provided samples 3 months postoperatively to be used as a pooled control sample population. A discrimination classifier was identified for eNose and subsequently, sensitivity and specificity values were determined. Leave-one-out cross-validation was performed. RESULTS: Using leave-one-out cross-validation the eNose reached a sensitivity of 78%, a specificity of 67% and AUC 0.77. CONCLUSIONS: The electronic nose is capable of rapidly and noninvasively discriminating prostate cancer and benign prostatic hyperplasia using urine headspace in patients undergoing surgery.

Poststroke dementia is associated with recurrent ischaemic stroke.

OBJECTIVE: To investigate whether poststroke dementia (PSD) diagnosed after ischaemic stroke predicts recurrent ischaemic stroke in long-term follow-up. METHODS: We included 486 consecutive patients with ischaemic stroke (388 with first-ever stroke) admitted to Helsinki University Central Hospital who were followed-up for 12 years. Dementia was diagnosed in 115 patients using the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition (DSM-III) criteria. The effects of risk factors and  PSD on survival free of recurrent stroke were estimated using Kaplan-Meier log-rank analyses, and the HRs for stroke recurrence were calculated using Cox proportional hazards models. RESULTS: In the entire cohort, patients with PSD had a shorter mean time to recurrent stroke (7.13 years, 95% CI 6.20 to 8.06) than patients without dementia (9.41 years, 8.89 to 9.92; log rank p<0.001). This finding was replicated in patients with first-ever stroke (6.89 years, 5.85 to 7.93 vs 9.68 years, 9.12 to 10.24; p<0.001). In Cox univariate analysis, PSD was associated with increased risk for recurrent stroke both in the entire cohort (HR 2.02; 95% CI 1.47 to 2.77) and in those with first-ever stroke (2.40; 1.68 to 3.42). After adjustment for the significant covariates of age, atrial fibrillation, peripheral arterial disease and hypertension, PSD was associated with increased risk for recurrent stroke both in the entire cohort (1.84; 1.34 to 2.54) and in those with first-ever stroke (2.16; 1.51 to 3.10). CONCLUSIONS: Poststroke dementia predicts recurrence of ischaemic stroke in long-term follow-up and should be considered when estimating prognosis.

Post-stroke depression and depression-executive dysfunction syndrome are associated with recurrence of ischaemic stroke.

BACKGROUND: Depression and depression-executive dysfunction syndrome (DES) are common neuropsychiatric consequences of stroke. We hypothesized that if stroke as a cerebrovascular event causes depression, this so-called post-stroke depression will further increase the risk of recurrent stroke. The objective of the study was to investigate whether patients with post-stroke depression or DES have increased rates of stroke recurrence. METHODS: We included 223 patients from the Helsinki Stroke Aging Memory cohort (n = 486) admitted to Helsinki University Central Hospital with a follow-up of 12 years. We included only patients with first-ever ischaemic stroke who were testable for depression and executive dysfunction. For follow-up, national register data were reviewed for all diagnosis codes of ischaemic stroke, survival data and causes of death. Neuropsychological and neuropsychiatric evaluations for depression and executive functions were performed 12-20 weeks after the index stroke. Univariate analysis was performed using χ(2), Mantel-Haenszel, ANOVA, and Kaplan-Meier log rank analyses. A Cox multivariable model with forced entry was used to adjust for stroke risk factors (age, gender, smoking, atrial fibrillation, hypertension, diabetes, peripheral arterial disease, hypercholesterolaemia). RESULTS: The mean time to first recurrent stroke was shorter for the depressed patient group (8.15, 95% CI 7.11-9.19 vs. 9.63, 8.89-10.38 years) and even shorter for patients with DES (7.15, 5.55-8.75 vs. 9.75, 9.09-10.41 years) compared to the remaining groups, respectively. The cumulative risk for recurrent ischaemic stroke in the 12-year follow-up was higher for the depression group (log rank p = 0.04) and for the DES group (log rank p = 0.01) compared to the remaining groups, respectively. Cox multivariable analyses revealed that the older age of the patient (1.05; 1.01-1.08/year), the absence of hypercholesterolaemia (0.24; 0.09-0.59), depression (1.68; 1.07-2.63), and DES (1.95; 1.14-3.33) were all associated with recurrent stroke. CONCLUSIONS: Depression and especially DES are associated with a shorter interval to recurrence of ischaemic stroke but executive dysfunction alone is not associated with a more rapid stroke recurrence. Diagnosis and treatment of depressive syndromes should be considered as a part of secondary prevention in patients with ischaemic stroke.

Psoas muscle quantified muscle status and long-term mortality after cardiovascular interventions.

RESULTS: In the meta-analysis, psoas muscle measurements were significantly associated with mortality among men (p < 0.05), with high heterogeneity in the associations across all cohorts. There was very little difference in the association between PMA and PMD and mortality (HR 0.83, 95% CI 0.69-0.99, p = 0.002; HR 0.85, 95% CI 0.77-0.94, p = 0.041 for one SD increase in PMA and PMD in the random effects model). Combining PMA and PMD into one composite variable by multiplying their values together showed the most robust association in terms of the magnitude of the effect size in men (HR, 0.77; 95% CI 0.73-0.87, p < 0.001). Indexing PMA to body size did not result in any significant differences in this association. Among women, psoas muscle measurements were not associated with long-term mortality in this meta-analysis. CONCLUSIONS: Different psoas muscle measurements were significantly and very similarly associated with mortality among men but not among women. No single measurement stands out, although combining PMA and PMD seems to be a slightly stronger estimate in terms of effect size and should be considered in further studies.

Significant sarcopenia affecting survival in patients undergoing heavy invasive operations may be preoperatively assessed using images of psoas muscle (PM) from routine computerized tomography but the optimal method for evaluation is unclear. A meta-analysis of individual participant data of over two thousand patients undergoing cardiovascular interventions shows that different PM measurements of surface area and density were significantly and very similarly associated with mortality among men but not among women. Combining PM area with PM density to one estimate of lean psoas muscle area seems to provide the strongest hazard estimate among men.

Detection of smell print differences between nonmalignant and malignant prostate cells with an electronic nose.

AIM: To determine whether an electronic nose can differentiate cultured nonmalignant and malignant prostatic cells from each other and whether the smell print is secreted to the surrounding medium. MATERIALS & METHODS: Prostatic nonmalignant (EP-156T and controls) and malignant (LNCaP) cell lines, as well as conditioned and unconditioned media, were collected. The smell prints of the samples were analyzed by a ChemPro(®) 100 electronic nose device. The data were normalized and dimension reduction was conducted. The samples were classified and misclassification rates were calculated. RESULTS: The electronic nose differentiated the nonmalignant and malignant cell lines from each other, achieving misclassification rates of 2.9-3.6%. Cells did not differ from the conditioned medium but differed from the unconditioned medium (misclassification rates: 0.0-25.6%). CONCLUSION: Malignant and nonmalignant prostatic cell lines have distinct smell prints. Prostatic cancer cells seem to modify the smell print of their medium.

Short stature is associated with coronary heart disease: a systematic review of the literature and a meta-analysis.

AIMS: The aim of this study was to assess the relationship between short stature and coronary heart disease (CHD) morbidity and mortality. METHODS AND RESULTS: We performed a systematic search from MEDLINE, PREMEDLINE, and All EBM Reviews as well as from a reference list of relevant articles. We used SPICO (Study design, Patient, Intervention, Control-intervention, Outcome) criteria. The methodological quality of studies was analysed by modified Borghoust criteria. From a total of 1907 articles, we selected 52 studies comprising population-based follow-up studies and patient cohorts followed after a CHD event, as well as case-control studies with height either as a continuous or categorical variable, totalling 3 012 747 individuals. The short ones were below 160.5 cm and tall ones over 173.9 cm on average. Among the shortest height category, the relative risks were 1.35 (95% CI 1.25-1.44) for all-cause mortality, 1.55 (1.37-1.74) for all cardiovascular disease (CVD) mortality, 1.49 (1.33-1.67) for CHD, and 1.52 (1.28-1.81) for myocardial infarction when compared with those within the highest height category. The mean relative risk was 1.46 (1.37-1.55). Short stature was associated with increased cardiovascular morbidity and mortality in both genders. CONCLUSION: The relationship between short stature and CVD appears to be a real one. On the basis of comparison, adults within the shortest category had an approximately 50% higher risk of CHD morbidity and mortality than tall individuals.

Post-stroke dementia and permanent institutionalization.

BACKGROUND: Dementia is among the most frequent causes of institutionalization. To serve the purpose of preventive strategies, there are no follow-up studies that have evaluated the actual impact of post-stroke dementia on institutionalization. We therefore compared the institutionalization rate and length of stay in an institutional care facility of patients with post-stroke dementia with stroke patients without dementia. METHODS: We included 410 consecutive patients aged 55 to 85 years with ischemic stroke who were admitted to Helsinki University Hospital (The SAM cohort). Hospitalization and nursing home admissions were reviewed from national registries. Dementia was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders 3rd edition (DSM-III) criteria using extensive clinical assessments performed 3 months post-stroke. The cohort had a follow-up 21 years later. RESULTS: Compared to patients without dementia, post-stroke dementia was associated with shorter survival time (6.60 vs 10.10 years, p < 0.001), shorter time spent not institutionalized (5.40 vs 9.37 years, p < 0.001), but not with time spent permanently institutionalized (0.73 vs 1.10 years, p = 0.08). Post-stroke dementia was associated with higher rates and earlier permanent institutionalization compared to absence of post-stroke dementia (HR 1.53, 95% CI 1.07-2.18) in a Cox regression model adjusting for age, status of living alone at baseline, modified Rankin Scale at baseline, history of atrial fibrillation, and cardiac failure. CONCLUSIONS: Post-stroke dementia is associated with earlier permanent institutionalization. Due to significantly shorter survival, the time spent in nursing homes was not significantly longer in patients with post-stroke dementia compared with patients without post-stroke dementia.

Risk of symptomatic venous thromboembolism after abdominal aortic aneurysm repair in long-term follow-up of 1021 consecutive patients.

OBJECTIVE: Venous thromboembolism (VTE), including deep venous thrombosis and pulmonary embolism (PE), is an infrequent but consequential and potentially preventable complication after major surgical procedures. The aim of the study was to describe the long-term occurrence of symptomatic VTE in patients undergoing abdominal aortic aneurysm (AAA) repair and to ascertain patient-specific risk factors as well as to compare the rate with that of a reference population. METHODS: The study included all patients who had undergone endovascular or open AAA repair, both elective and urgent/acute cases, at the Tampere University Hospital (Finland) between February 2001 and December 2016; 59% of patients had undergone endovascular and 41% open repair, and 23% of all cases had required urgent or emergency treatment. Information about later treatment episodes for symptomatic VTE and survival data were obtained from national registries. The reference population was obtained from national registries with a random sample of inhabitants matched for age, sex, and location of residence with a 4:1 ratio and was analyzed similarly. RESULTS: Altogether, 1021 patients and 4065 controls were included (88% male; median age, 74 years in both groups). The high-risk period for VTE lasted for approximately 3 months, and during that time, its occurrence was highest in patients with coronary disease (2.5%), after open repair (2.4%), and in an urgent or emergency setting (2.6%), whereas the rate was low after endovascular aneurysm repair (1.0%). The cumulative incidence of VTE at 3 months, 1 year, 3 years, and 5 years was 1.1%, 1.6%, 2.7%, and 4.5% in patients and 0.1%, 0.3%, 1.0%, and 1.8% in the reference population, respectively (P < .001 each). Most VTE events were PE in the patient group. The 5-year mortality rates were 37.9% in patients and 23.8% in controls (P < .001). CONCLUSIONS: The incidence of symptomatic VTE, particularly PE, after AAA repair is significant, in both short-term and long-term follow-up. Open surgery, acute setting, and concomitant coronary disease appear to increase the risk.

Cerebral small vessel disease and kidney function predict long-term survival in patients with acute stroke.

BACKGROUND AND PURPOSE: Cerebral small vessel disease reflected by white matter lesions (WMLs) in MRI and kidney function reflected by estimated glomerular filtration rate (eGFR) is closely associated in patients without stroke. We studied whether eGFR and WMLs predict long-term survival in patients with acute stroke. METHODS: After exclusion of patients with low eGFR (N=5 [1.3%]; <30 mL/min/1.73 m(2)), consecutive patients with acute stroke (N=378) subjected to MRI and serum creatinine determination were included in the study and prospectively followed-up up to 12 years. RESULTS: Of the patients, 71.2% had died during the follow-up, 152 (40.2%) had moderate (eGFR <60 mL/min/1.73 m(2)), and 226 (59.8%) had normal or mildly impaired eGFR (>or=60 mL/min/1.73 m(2)). Of the patients, 108 (28.6%) had mild, 68 (18.0%) had moderate, and 202 (53.4%) had severe WMLs. In logistic regression analysis adjusted with age and sex, eGFR <60 mL/min/1.73 m(2) was associated with severe WMLs (relative risk 2.77, 95% CI 1.10 to 6.98, P=0.030). In Cox regression survival analysis adjusted with significant covariates, eGFR <60 mL/min/1.73 m(2) (1.30, 95% CI 1.00 to 1.68, P=0.047) and severe WMLs (hazard ratio 1.32, 95% CI 1.02 to 1.71, P=0.033) were associated with poor survival, whereas they were not independent from each other. In further analyses, presence of either eGFR >or=60 mL/min/1.73 m(2) or only mild to moderate WMLs, or both, was associated with improved survival compared with all other combinations. CONCLUSIONS: Cerebral small vessel disease is closely associated with kidney function in patients with acute stroke. Cerebral small vessel disease and kidney function are closely associated predictors of poor poststroke survival.

Depression-executive dysfunction syndrome relates to poor poststroke survival.

BACKGROUND: The aim of this study was to investigate the influence of poststroke depression and executive dysfunction on long-term survival after acute stroke. METHODS: A total of 257 consecutive acute ischemic stroke patients were included in the study and followed up to 12 years. Depression was diagnosed 3 months after stroke in 99 patients (38.5%). FINDINGS: In Kaplan-Meier analysis, there was no difference in survival of patients with and without poststroke depression (8.7 versus 8.3 years). Instead, patients with both depression and executive dysfunction had shorter median survival than patients with neither depression nor executive dysfunction (6.6 versus 10.3 years). Comparison between all patients with executive dysfunction and patients without it, not regarding depressive status, showed that executive dysfunction in itself was strongly associated with poor poststroke survival (6.4 versus 10.6 years). In stepwise Cox regression proportional hazards analysis adjusted with covariates, poststroke depression with executive dysfunction (hazard ratio [HR] 1.63) and advanced age (HR 1.11) remained as independent predictors of poor long-term survival. INTERPRETATION: The authors' well-defined poststroke cohort with long-term follow-up indicates that in poststroke depression, the depression-executive dysfunction syndrome is the predictor of poor long-term survival rather than depression in itself.

Alpha-lipoic acid does not alter stress protein response to acute exercise in diabetic brain.

Heat shock proteins (HSPs) are molecular chaperones which may act protective in cerebrovascular insults and peripheral diabetic neuropathy. We hypothesized that alpha-lipoic acid (LA), a natural thiol antioxidant, may enhance brain HSP response in diabetes. Rats with or without streptozotocin-induced diabetes were treated with LA or saline for 8 weeks. Half of the rats were subjected to exhaustive exercise to investigate HSP induction, and the brain tissue was analyzed. Diabetes increased constitutive HSC70 mRNA, and decreased HSP90 and glucose-regulated protein 75 (GRP75) mRNA without affecting protein levels. Exercise increased HSP90 protein and mRNA, and also GRP75 and heme oxygenase-1 (HO-1) mRNA only in non-diabetic animals. LA had no significant effect on brain HSPs, although LA increased HSC70 and HO-1 mRNA in diabetic animals and decreased HSC70 mRNA in non-diabetic animals. Eukaryotic translation elongation factor-2, essential for protein synthesis, was decreased by diabetes and suggesting a mechanism for the impaired HSP response related to translocation of the nascent chain during protein synthesis. LA supplementation does not offset the adverse effects of diabetes on brain HSP mRNA expression. Diabetes may impair HSP translation through elongation factors related to nascent chain translocation and subsequent responses to acute stress.

Diabetes impairs exercise training-associated thioredoxin response and glutathione status in rat brain.

Regular exercise plays an important preventive and therapeutic role in oxidative stress-associated diseases such as diabetes and its complications. Thiol antioxidants including thioredoxin (TRX) and glutathione (GSH) have a crucial role in controlling cellular redox status. In this study, the effects of 8 wk of exercise training on brain TRX and GSH systems, and antioxidant enzymes were tested in rats with or without streptozotocin-induced diabetes. We found that in untrained animals, the levels of TRX-1 (TRX1) protein and activity, and thioredoxin-interacting protein (TXNip) were similar in diabetic and nondiabetic animals. Exercise training, however, increased TRX1 protein in nondiabetic animals without affecting TXNip levels, whereas diabetes inhibited the effect of training on TRX1 protein and also increased TXNip mRNA. In addition, the proportion of oxidized glutathione (GSSG) to total GSH was increased in animals with diabetes, indicating altered redox status and possibly increased oxidative stress. Glutathione peroxidase-1 (GPX1) levels were not affected by diabetes or exercise training, although diabetes increased total GPX activity. Both diabetes and exercise training decreased glutathione reductase (GRD) activity and cytosolic superoxide dismutase (Cu,Zn-SOD) levels. Nevertheless, diabetes or training had no effect on Cu,Zn-SOD mRNA, Mn-SOD protein, total SOD activity, or catalase mRNA, protein, or activity. Our findings suggest that exercise training increases TRX1 levels in brain without a concomitant rise in TXNip, and that experimental diabetes is associated with an incomplete TRX response to training. Increased oxidative stress may be both a cause and a consequence of perturbed antioxidant defenses in the diabetic brain.

Altered Polyamine Profiles in Colorectal Cancer.

BACKGROUND: The declining mortality rate of patients with colorectal cancer (CRC) can be explained, at least partially, with early diagnosis. Simple diagnostic methods are needed to achieve a maximal patient participation rate in screening. MATERIALS AND METHODS: Liquid chromatography electrospray tandem mass spectrometry (LC-MS/MS) was used to determine urinary polyamine (PA) profiles. In a prospective setting, 116 patients were included in the study: 57 with CRC, 13 with inflammatory bowel disease (IBD), 12 with adenoma, and 34 controls. RESULTS: N1,N12-diacetylspermine (DiAcSPM) level was significantly higher in patients with CRC than controls (sensitivity=78.0%, specificity=70.6%; p=0.00049). The level of diacetylated cadaverine (p=0.0068) was lower and that of diacetylated putrescine (p=0.0078) was higher in patients with CRC than in those with IBD. Cadaverine (p=0.00010) and spermine (p=0.042) levels were lower and that of DiAcSPM (p=0.018) higher in patients with CRC than in those with adenoma. CONCLUSION: The simultaneous determination of urinary PAs by means of LC-MS/MS can be used to discriminate CRC from controls and patients with benign colorectal diseases.