Clinical and neuroanatomical predictors of post-stroke fatigue.

INTRODUCTION: Post-stroke fatigue (PSF) has been described as early exhaustion with tiredness that develops during physical or mental activity and generally does not improve with rest. There are inconsistent findings on the relationship between the characteristics of the ischemic brain lesion and PSF. However, some studies suggest that specific neuroanatomical and neuroplastic changes could explain post-stroke fatigue. The aim was to evaluate the severity of PSF in relation to the location and the size of the ischemic lesion in acute stroke patients to establish possible predictors of PSF. PATIENTS AND METHODS: We performed a prospective observational study to establish potential early predictors of long-term PSF, which was assessed using the Fatigue Assessment Scale six months after ischemic stroke. After segmenting brain infarcts on Diffusion-Weighted Imaging (DWI) images, we studied the association with PSF using Voxel-Based Lesion-Symptom Mapping (VLSM). RESULTS: Out of 104 patients, 61 (59 %) reported PSF. Female sex and history of diabetes mellitus were associated with a greater risk of developing PSF. The association of PSF with female sex was confirmed in a replication cohort of 50 patients. The ischemic lesion volume was not associated with PSF, and VBLSM analysis did not identify any specific brain area significantly associated with PSF. CONCLUSIONS: PSF is frequent in stroke patients, especially women, even after six months. The absence of neuroanatomical correlates of PSF suggests that it is a multifactorial process with biological, psychological, and social risk factors that require further study.

Stroke units could be a valid alternative to intensive care units for patients with low-grade aneurysmal subarachnoid haemorrhage.

BACKGROUND AND PURPOSE: According to current guidelines, patients with aneurysmal subarachnoid haemorrhage (aSAH) are mostly managed in intensive care units (ICUs) regardless of baseline severity. We aimed to assess the prognostic and economic implications of initial admission of patients with low-grade aSAH into a stroke unit (SU) compared to initial ICU admission. METHODS: We reviewed prospectively registered data from consecutive aSAH patients with a World Federation of Neurosurgery Societies grade <3, admitted to our Comprehensive Stroke Centre between April 2013 and September 2018. Clinical and radiological baseline traits, in-hospital complications, length of stay (LOS) and poor outcome at 90 days (modified Rankin Scale score > 2) were compared between the ICU and SU groups in the whole population and in a propensity-score-matched cohort. RESULTS: Of 131 patients, 74 (56%) were initially admitted to the ICU and 57 (44%) to the SU. In-hospital complication rates were similar in the ICU and SU groups and included rebleeding (10% vs. 7%; P = 0.757), angiographic vasospasm (61% vs. 60%; P = 0.893), delayed cerebral ischaemia (12% vs. 12%; P = 0.984), pneumonia (6% vs. 4%; P = 0.697) and death (10% vs. 5%; P = 0.512). LOS did not differ between groups (median [interquartile range] 22 [16-30] vs. 19 [14-26] days; P = 0.160). In adjusted multivariate models, the location of initial admission was not associated with long-term poor outcome either in the whole population (odds ratio [OR] 1.16, 95% confidence interval [CI] 0.32-4.19; P = 0.825) or in the matched cohort (OR 0.98, 95% CI 0.24-4.06; P = 0.974). CONCLUSIONS: A dedicated SU, with care from a multidisciplinary team, might be an optimal alternative to ICU for initial admission of patients with low-risk aSAH.

Rivaroxaban versus aspirin for secondary prevention of ischaemic stroke in patients with cancer: a subgroup analysis of the NAVIGATE ESUS randomized trial.

BACKGROUND AND PURPOSE: Cancer is a frequent finding in ischaemic stroke patients. The frequency of cancer amongst participants in the NAVIGATE ESUS randomized trial and the distribution of outcome events during treatment with aspirin and rivaroxaban were investigated. METHODS: Trial participation required a recent embolic stroke of undetermined source. Patients' history of cancer was recorded at the time of study entry. During a mean follow-up of 11 months, the effects of aspirin and rivaroxaban treatment on recurrent ischaemic stroke, major bleeding and all-cause mortality were compared between patients with cancer and patients without cancer. RESULTS: Amongst 7213 randomized patients, 543 (7.5%) had cancer. Of all patients, 3609 were randomized to rivaroxaban [254 (7.0%) with cancer] and 3604 patients to aspirin [289 (8.0%) with cancer]. The annual rate of recurrent ischaemic stroke was 4.5% in non-cancer patients in the rivaroxaban arm and 4.6% in the aspirin arm [hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.78-1.24]. In cancer patients, the rate of recurrent ischaemic stroke was 7.7% in the rivaroxaban arm and 5.4% in the aspirin arm (HR 1.43, 95% CI 0.71-2.87). Amongst cancer patients, the annual rate of major bleeds was non-significantly higher for rivaroxaban than aspirin (2.9% vs. 1.1%; HR 2.57, 95% CI 0.67-9.96; P for interaction 0.95). All-cause mortality was similar in both groups. CONCLUSIONS: Our exploratory analyses show that patients with embolic stroke of undetermined source and a history of cancer had similar rates of recurrent ischaemic strokes and all-cause mortality during aspirin and rivaroxaban treatments and that aspirin appeared safer than rivaroxaban in cancer patients regarding major bleeds. www.clinicaltrials.gov (NCT02313909).

Joint study of the associations of HLA-B and the transmembrane short tandem repeat polymorphism of MICA protein with alopecia areata shows independent associations of both with the disease.

BACKGROUND: Alopecia areata (AA) is a skin disease that produces hair loss in patches of skin. The underlying mechanism of AA is a loss of immune privilege of hair follicles, which are then attacked by natural killer (NK) cells. A previous genome-wide association study linked single nucleotide polymorphisms of the protein MHC class I chain-related A (MICA) to this disease. MICA is the ligand for the activating receptor NKG2D, expressed mainly by NK cells and CD8+ cytotoxic T cells. As the aforementioned study did not include short tandem repeats (STRs) of MICA, we decided to study these in relation to AA. AIM: To study the association of STRs with AA, alongside that of human leucocyte antigen (HLA) locus B, which is closely linked to MICA. METHODS: DNA amplicon size analysis was carried out, and HLA-B locus genomic typing was performed by PCR-sequence-specific oligonucleotide analysis. RESULTS: We observed an association between AA and both MICA*009 and HLA-B14; associations were also observed between HLA-B alleles and MICA alleles, which have both been previously found to be connected with AA, but never studied together. CONCLUSIONS: We conclude that it is important to study HLA-B and MICA together to avoid the influence of their association in experiments in which they are investigated separately.

Experiences of caregiving and quality of healthcare among caregivers of patients with complex chronic processes: A qualitative study.

Aim To explore the perceptions of main caregivers regarding caring for chronic complex patients in two different regions of Spain. BACKGROUND: Spain is a country with an ageing population and a high number of people with chronic diseases. It is well known that the role of the caregiver is important to ensure quality of life and appropriate care. METHODS: Qualitative design using focus groups. Five focus groups, from two different regions, were conducted with 22 caregivers of people with chronic complex diseases to explore their personal experience, examine the quality of care received by the patient and their family and to develop strategies for the improvement of the quality of health care. The focus groups were audio and video recorded. The transcriptions of the focus group sessions were exported to qualitative software analysis MAXQDA 2018.2. The qualitative content analysis was based on different analytical cycles. RESULTS: In general terms, caregivers would refer to accepting the care of their family members, but they highlight many negative aspects such as tiredness, lack of help and overload of care. They indicated general satisfaction with the health system but indicated that help was insufficient and that strategies to better address the situations of the complex chronic patient should be improved. The main categories observed were: Conclusions. Complex chronic illnesses are increasingly common at present, generating important consequences on the lives of patients and that of their caregivers. The design of any health strategy for facing the dilemma of chronic illnesses, must necessarily include the vision of the caregivers.

Clinical results of infrared coagulation as a treatment of high-grade anal dysplasia: a systematic review.

BACKGROUND: Anal intraepithelial neoplasia (AIN) (or low/high grade squamous intraepithelial neoplasia (L/HSIL)) is the precursor of anal of early invasive anal cancer. Different treatment options for local ablation of localized lesions have been reported. The aim of this study was to analyze the clinical efficacy and safety of infrared coagulation for the treatment of anal dysplasia. METHODS: A search of the literature was performed in 2019 using PubMed and Cochrane to identify all eligible trials published reporting data on the treatment of anal dysplasia with infrared coagulation. The percentage of squamous cell carcinoma of the the anus that developed in the follow-up and results on major complications after treatment were the primary outcomes. RESULTS: Twenty-four articles were identified from which 6 were selected with a total of 360 patients included, with a median age of 41.8 years. Three studies were prospective and 3 retrospective, only one was a randomized trial. All articles included males, 4 articles included HIV-positive women and only one article included non HIV infected males. No patient developed major complications after infrared coagulation therapy. Pain was the most common symptom found after the procedure in the different series and mild bleeding that did not require transfusion was the most common complication occurring in 4 to 78% of patients. Median follow-up was between 4.7 and 69 months. No patient developed squamous cell carcinoma after infrared treatment. Recurrent HSIL varied from 10 to 38%. Two studies reported results from follow-up of untreated patients showing that between 72 and 93% of them had persistent HSIL at last follow-up and 4.8% developed squamous cell carcinoma. CONCLUSIONS: Infrared coagulation is a safe and effective method for ablation of high-grade anal dysplasia that could help prevent anal cancer. Continued surveillance is recommended due to the risk of recurrence.

MICA*A4 protects against ulcerative colitis, whereas MICA*A5.1 is associated with abscess formation and age of onset.

Ulcerative colitis (UC) is one of the two major forms of inflammatory bowel disease, the aetiology of which remains unknown. Several studies have demonstrated the genetic basis of disease, identifying more than 130 susceptibility loci. The major histocompatibility complex class I chain-related gene A (MICA) is a useful candidate to be involved in UC pathogenesis, because it could be important in recognizing the integrity of the epithelial cell and its response to stress. The aim of this study was to analyse the relationship between polymorphisms in the transmembrane domain of MICA and susceptibility to develop UC. A total of 340 patients with UC and 636 healthy controls were genotyped for MICA transmembrane polymorphism using a polymerase chain reaction (PCR) combined with fluorescent technology. Different MICA alleles were determined depending on the PCR product size. The allele MICA*A4 was less frequent in patients than in controls (P = 0·003; OR = 0·643), and this protective role is higher when it forms haplotype with B*27 (P = 0·002; OR = 0·294). The haplotype HLA-B*52/MICA*A6 was also associated with UC [P = 0·001; odds ratio (OR) = 2·914]. No other alleles, genotypes or haplotypes were related with UC risk. Moreover, MICA*A5.1 is associated independently with abscesses (P = 0·002; OR = 3·096) and its frequency is lower in patients diagnosed between ages 17 and 40 years (P = 0·007; OR = 0·633), meaning an extreme age on onset. No association with location, extra-intestinal manifestations or need for surgery was found.

Association between low 25-hydroxyvitamin D, insulin resistance and arterial stiffness in nondiabetic women with systemic lupus erythematosus.

OBJECTIVE: The objective of this paper is to examine if there is an association between low levels of 25-hydroxyvitamin D (25(OH)D) and insulin resistance (IR) in nondiabetic women with systemic lupus erythematosus (SLE) and to evaluate its impact on arterial stiffness. PATIENTS AND METHODS: In this cross-sectional study 25(OH)D, insulin, insulin resistance measured by the homeostatic model assessment (HOMA-IR), homocysteine, fibrinogen, characteristics of SLE, medications and pulse-wave velocity (PWV) were measured in 106 nondiabetic women with SLE and 101 matched controls. RESULTS: Women with SLE tended to have lower 25(OH)D levels (p = 0.078) and a higher frequency of 25(OH)D deficiency (defined as < 10 ng/ml) than controls (p = 0.058). Patients from the lowest quartile of the 25(OH)D range had higher PWV (p = 0.043), fasting glucose (p = 0.035), insulinemia (p ≤ 0.001), HOMA-IR (p = 0.006), C4 (p = 0.012), as well as more frequent IR (p = 0.002) and metabolic syndrome (p = 0.052) than those in the upper quartile, and no differences were found in age, body mass index (BMI), blood pressure, lipid levels and renal function. In women with SLE, 25(OH)D inversely correlated with insulin (p = 0.006), HOMA-IR (p = 0.008) and C4 (p = 0.048) and tended to correlate with fibrinogen (p = 0.060) after adjustment for BMI, age, SLEDAI, prednisone dose, renal function, inflammation markers and seasonal variation, but not with PWV. In controls, 25(OH)D correlated only with homocysteine after the same adjustment, and the correlation with PWV tended to be significant after adjustment for BMI and age (r = -0.190, p = 0.10). CONCLUSION: Low 25(OH)D levels were found to be associated with increased IR in nondiabetic women with SLE independently of BMI. Low 25(OH)D levels, but not IR, could be associated with increased arterial stiffness in these patients.

Cancer-Associated Thrombotic Microangiopathy: Literature Review and Report of Five Cases.

Thrombotic microangiopathy (TMA) is an anatomopathological lesion mediated by endothelial dysfunction and characterized by the creation of microthrombi in small vessels. In patients with cancer, it may be due to toxicity secondary to chemotherapy, tumor embolization, or hematopoietic progenitor transplantation. Cancer-associated TMA is an underestimated entity that generally appears in the final stages of the disease, although it may also be the initial manifestation of an underlying cancer. Support treatment is necessary in all cases and, depending on the cause, different targeted therapies may be used. The prognosis is very poor. In this article we present a comprehensive review of the existing literature on the physiological mechanisms of cancer-associated TMA. Afterwards, five clinical cases will be presented of patients who developed TMA and were diagnosed in our Department in 2023. We present a discussion of the different causes that triggered the condition, the possible reasons behind the underestimation of this pathology, and the measures that may be adopted.

Optimizing the Definition of Ischemic Core in CT Perfusion: Influence of Infarct Growth and Tissue-Specific Thresholds.

BACKGROUND AND PURPOSE: CTP allows estimating ischemic core in patients with acute stroke. However, these estimations have limited accuracy compared with MR imaging. We studied the effect of applying WM- and GM-specific thresholds and analyzed the infarct growth from baseline imaging to reperfusion. MATERIALS AND METHODS: This was a single-center cohort of consecutive patients (n = 113) with witnessed strokes due to proximal carotid territory occlusions with baseline CT perfusion, complete reperfusion, and follow-up DWI. We segmented GM and WM, coregistered CTP with DWI, and compared the accuracy of the different predictions for each voxel on DWI through receiver operating characteristic analysis. We assessed the yield of different relative CBF thresholds to predict the final infarct volume and an estimated infarct growth-corrected volume (subtracting the infarct growth from baseline imaging to complete reperfusion) for a single relative CBF threshold and GM- and WM-specific thresholds. RESULTS: The fixed threshold underestimated lesions in GM and overestimated them in WM. Double GM- and WM-specific thresholds of relative CBF were superior to fixed thresholds in predicting infarcted voxels. The closest estimations of the infarct on DWI were based on a relative CBF of 25% for a single threshold, 35% for GM, and 20% for WM, and they decreased when correcting for infarct growth: 20% for a single threshold, 25% for GM, and 15% for WM. The combination of 25% for GM and 15% for WM yielded the best prediction. CONCLUSIONS: GM- and WM-specific thresholds result in different estimations of ischemic core in CTP and increase the global accuracy. More restrictive thresholds better estimate the actual extent of the infarcted tissue.

Improvements in the Effectiveness of Early Detection in Colorectal Cancer with Open-Label Randomised Study.

INTRODUCTION: The general objective of this research is to improve the quality of colorectal cancer screening (CRC) by assessing, as an indicator of effectiveness, the ability of colonoscopy to detect more advanced adenomas in the exposed group than in the control group. MATERIAL AND METHODS: The present work is designed as an open-label randomized study on cancer screening, using two groups based on their exposure to the protocol: an exposed to intervention group (EIG, 167), and a control group (CG, 167), without the intervention of the protocol and by 1:1 matching. RESULTS: In 167 patients in the GEI, 449 polyps are visualized and 274 are adenomas (80.58%), of which 100 (36.49%) are advanced adenomas. In the CG (n = 174), there are 321 polyps and 152 adenomas (82.60%). The variables significantly associated by logistic regression to the detection of adenomas are the male sex with an OR of 2.52. The variable time to withdrawal, ≥9 min, is significant at 99% confidence (p = 0.002/OR 34.67) and the fractional dose is significant at 99% (p = 0.009, OR 7.81). CONCLUSION: Based on the observations made, our study suggests that the intervention in collaboration between primary care and hospital care is effective from a preventive point of view and achieves the objective of effectiveness and quality of the PCCR.

Correlation of asymptomatic hyperuricaemia and serum uric acid levels with arterial stiffness in women with systemic lupus erythematosus without clinically evident atherosclerotic cardiovascular disease.

The objective of this article was to evaluate whether serum uric acid (SUA) correlates with arterial stiffness and inflammation markers in a cohort of women with systemic lupus erythematosus (SLE) without overt atherosclerotic cardiovascular diseases, who attended a community hospital. One hundred and two women with SLE were assessed as part of this cross-sectional study. Carotid-femoral pulse wave velocity (PWV) was measured using an automatic device (Complior). C-reactive protein (CRP), fibrinogen and homocysteine levels as well as other metabolic results were recorded. Duration and activity of SLE, damage accrual and treatments were recorded. SLE women were categorized as having or not having hyperuricaemia (HU) according to SUA levels (greater than or up to 6.2 mg/dl, respectively). A multiple linear regression analysis was used to determine the independent link between SUA levels and other variables. Women with SLE and HU (n = 15, 15%) had a worse cardiovascular risk profile that included ageing, hypertension, obesity, higher total cholesterol levels, renal failure and presence of metabolic syndrome. Also, the duration of SLE was increased and damage accrual was greater. In the unadjusted analysis, SUA levels correlated with PWV, CRP, fibrinogen and homocysteine. However, in a multivariate linear regression analysis, SUA levels independently correlated with the duration of SLE, creatinine, total cholesterol and homocysteine levels but did not correlate with PWV. In conclusion, SUA was associated with arterial stiffness, but not independently of age and homocysteine levels. Nevertheless, SUA might be an ancillary indicator of subclinical atherosclerosis in SLE women without clinically evident atherosclerotic cardiovascular disease.

Harms and benefits of lymphocyte subpopulations in patients with acute stroke.

UNLABELLED: Lymphocytes are major players in the development of innate and adaptive immune responses but their behavior in patients with acute stroke has received little attention. EXPERIMENTAL PROCEDURES: Using flow cytometry we identified total lymphocytes, T cells, helper T (Th) cells, cytotoxic T lymphocytes (CTL), natural killer (NK) cells, B cells, and regulatory T (Treg) cells in 46 consecutive patients with acute stroke within a median of 180 min of clinical onset, and at days 2, 7, and 90. Daily neurological score (National Institutes of Health Stroke Scale), diffusion-weighted imaging on brain magnetic resonance imaging, functional impairment, and stroke-associated infection (SAI) at day 7 were assessed. Apoptosis in lymphocyte subsets, tumor necrosis factor (TNF) -alpha/interleukin (IL) -4 production in stimulated Th and CTL, cluster of differentiation 86 (CD86) (B7-2) expression in B cells, cortisol and metanephrine in serum were measured. Multivariate analyses were used to evaluate SAI, and stroke outcome. RESULTS: Increased apoptosis and a fall of T, Th, CTL, B, and Treg cells were observed after stroke. Severer stroke on admission and SAI disclosed a greater decline of T, Th, and CTL cells. Increased cortisol and metanephrine was associated with severe stroke and SAI, and inversely correlated with T, and CTL. T cells, and CTL were correlated with infarct growth. Stroke but not SAI resulted in lower TNF-alpha production in Th cells. SAI showed the greatest fall of lymphocytes, T, Th, and CTL, but not B cells, or Treg. Poor outcome was associated with reduced levels of B cells, and increased expression of CD86 in B cells, but not with SAI. CONCLUSION: Lymphopenia and increased apoptosis of T, Th, CTL, Treg and B cells are early signatures after human stroke. A decreased cellular response after stroke is a marker of ongoing brain damage, the stress response, and a higher risk of infection. A lower humoral response is predictor of poorer long-term outcome.

Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study.

BACKGROUND: Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. METHODS AND RESULTS: The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged > or =55 years, having suffered an ischemic stroke (< or =3 months) or a transient ischemic attack (< or =8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2-4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. CONCLUSIONS: The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event.

The Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack (PERFORM) study: baseline characteristics of the population.

BACKGROUND: The Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack (PERFORM) study is an international double-blind, randomized controlled trial designed to investigate the superiority of the specific TP receptor antagonist terutroban (30 mg/day) over aspirin (100 mg/day), in reducing cerebrovascular and cardiovascular events in patients with a recent history of ischemic stroke or transient ischemic attack. Here we describe the baseline characteristics of the population. METHODS AND RESULTS: Parameters recorded at baseline included vital signs, risk factors, medical history, and concomitant treatments, as well as stroke subtype, stroke-associated disability on the modified Rankin scale, and scores on scales for cognitive function and dependency. Eight hundred and two centers in 46 countries recruited a total of 19,119 patients between February 2006 and April 2008. The population is evenly distributed and is not dominated by any one country or region. The mean +/- SD age was 67.2 +/- 7.9 years, 63% were male, and 83% Caucasian; 83% had hypertension, and about half the population smoked or had quit smoking. Ninety percent of the qualifying events were ischemic stroke, 67% of which were classified as atherothrombotic or likely atherothrombotic (pure or coexisting with another cause). Modified Rankin scale scores showed slight or no disability in 83% of the population, while the scores on the Mini-Mental State Examination, Isaacs' Set Test, Zazzo's Cancellation Test, and the instrumental activities of daily living scale showed a good level of cognitive function and autonomy. CONCLUSIONS: The PERFORM study population is homogeneous in terms of demographic and disease characteristics. With 19,119 patients, the PERFORM study is powered to test the superiority of terutroban over aspirin in the secondary prevention of cerebrovascular and cardiovascular events in patients with a recent history of ischemic stroke or transient ischemic attack.

Leukoaraiosis May Confound the Interpretation of CT Perfusion in Patients Treated with Mechanical Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Leukoaraiosis frequently coexists in patients with acute stroke. We studied whether leukoaraiosis could confound the interpretation of CTP findings in patients treated with mechanical thrombectomy. MATERIALS AND METHODS: We analyzed 236 patients with stroke treated with mechanical thrombectomy and studied with CTP, of whom 127 (53.8%) achieved complete reperfusion. Periventricular white matter hyperintensities on MR imaging and hypodensities on NCCT were assessed through the Fazekas score. CTP-predicted nonviable tissue was defined as relative CBF <30%, and final infarct volume was quantified in DWI. We estimated mean MTT, CBV, and CBF in the asymptomatic hemisphere. In patients achieving complete reperfusion, we assessed the accuracy of nonviable tissue to predict final infarct volume using the intraclass correlation coefficient across periventricular hyperintensity/hypodensity Fazekas scores and variable relative CBF cutoffs. RESULTS: MTT was longer (Spearman ρ = 0.279, P < .001) and CBF was lower (ρ = -0.263, P < .001) as the periventricular hyperintensity Fazekas score increased, while CBV was similar across groups (ρ = -0.043, P = .513). In the subgroup of patients achieving complete reperfusion, nonviable tissue-final infarct volume reliability was excellent in patients with periventricular hyperintensity Fazekas score grade 0 (intraclass correlation coefficient, 0.900; 95% CI, 0.805-0.950), fair in patients with periventricular hyperintensity Fazekas scores 1 (intraclass correlation coefficient, 0.569; 95% CI, 0.327-0.741) and 2 (intraclass correlation coefficient, 0.444; 95% CI, 0.165-0.657), and poor in patients with periventricular hyperintensity Fazekas score 3 (intraclass correlation coefficient, 0.310; 95% CI, -0.359-0.769). The most accurate cutoffs were relative CBF <30% for periventricular hyperintensity Fazekas score grades 0 and 1, relative CBF <25% for periventricular hyperintensity Fazekas score 2, and relative CBF <20% for periventricular hyperintensity Fazekas score 3. The reliability analysis according to periventricular hypodensity Fazekas score grades on NCCT was similar to that in follow-up MR imaging. CONCLUSIONS: In patients with stroke, the presence of leukoaraiosis confounds the interpretation of CTP despite proper adjustment of CBF thresholds.

The response to IV rt-PA in very old stroke patients.

The use of rtPA in stroke patients aged >80 years remains controversial and it is debated whether there are sex-based differences in the response to rtPA. We assessed the clinical value of thrombolytic therapy in patients aged >80 years (elderly group) in comparison with a non-elderly group, and evaluated the existence of sex differences in the response to rtPA. All consecutive patients (n = 157) treated with rtPA were prospectively assessed since July 2001, including 49 elderly patients who fulfilled the National Institute of Neurological Disorders and Stroke (NINDS) criteria. Changes of the National Institute of Health Stroke Scale (NIHSS) score at 1 h, 24 h, and 7 days after rtPA administration, favourable outcome at day 90 [(modified Rankin Scale) mRS 0-1, or 2 if mRS = 2 before the stroke], symptomatic bleedings, and death rates were compared between elderly and non-elderly patients. Using logistic regression, baseline NIHSS score [odds ratio (OR) 0.59, 95% confidence interval (CI) 0.41-0.84] was an independent predictor of favourable outcome, but not sex (OR 0.72, 95% CI 0.33-1.56), or age >80 years (OR 0.74, 95% CI 0.32-1.70). The rates of clinical improvement, mortality, or symptomatic CNS bleeding were also unrelated to age and sex. In conclusion, the response to IV rtPA is not impaired in elderly stroke patients and male and female are equally responsive.

Heparin in acute ischemic stroke revisited.

The evidence gathered in clinical trials of low molecular weight heparins (LMWHs) or with unfractionated heparin (UH) given subcutaneously at low or medium doses to patients with acute stroke cannot be extrapolated to the insufficiently tested effects of intravenous, weight-adjusted UH. Recent small studies have provided encouraging results but are potentially confounded and deserve confirmation in larger randomized controlled trials. In accordance with the current understanding of the biology of acute ischemic stroke and the pharmacology of UH, the new randomized controlled trials on heparin should give appropriate credit to the importance of a short therapeutic window, adequate dose adjustment of the drug, intravenous administration, and close monitoring of biological effects. UH is an orphan drug and only an academic driven trial would be able to face such an enterprise. Meanwhile, recommendations against the value of "early" anticoagulation with full dose of weight adjusted UH in the setting of acute ischemic stroke are not based on direct evidence but on extrapolations.

First clinical symptom as a prognostic factor in systemic sclerosis: results of a retrospective nationwide cohort study.

The objective of the study is to determine the importance of the mode of onset as prognostic factor in systemic sclerosis (SSc). Data were collected from the Spanish Scleroderma Registry (RESCLE), a nationwide retrospective multicenter database created in 2006. As first symptom, we included Raynaud's phenomenon (RP), cutaneous sclerosis, arthralgia/arthritis, puffy hands, interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), and digestive hypomotility. A total of 1625 patients were recruited. One thousand three hundred forty-two patients (83%) presented with RP as first symptom and 283 patients (17%) did not. Survival from first symptom in those patients with RP mode of onset was higher at any time than those with onset as non-Raynaud's phenomenon: 97 vs. 90% at 5 years, 93 vs. 82% at 10 years, 83 vs. 62% at 20 years, and 71 vs. 50% at 30 years (p < 0.001). In multivariate analysis, factors related to mortality were older age at onset, male gender, dcSSc subset, ILD, PAH, scleroderma renal crisis (SRC), heart involvement, and the mode of onset with non-Raynaud's phenomenon, especially in the form of puffy hands or pulmonary involvement. The mode of onset should be considered an independent prognostic factor in systemic sclerosis and, in particular, patients who initially present with non-Raynaud's phenomenon may be considered of poor prognosis.

Interleukin 10, monocytes and increased risk of early infection in ischaemic stroke.

BACKGROUND AND PURPOSE: The pathophysiology of stroke-associated infection (SAI) is uncertain. The cytokine profile and peripheral white cell response were assessed in patients with or without SAI. METHODS: The incidence of SAI was assessed in 110 patients with ischaemic stroke allocated antibiotic prophylaxis or placebo within 24 h of clinical onset. Peripheral white cell counts, interleukin (IL)6, tumour necrosis factor (TNF)alpha and IL10 were measured in plasma. RESULTS: 17 (15%) patients developed infection and showed time-dependent increases of total white cell count, neutrophils, monocytes, lymphocytes, IL6 and IL10, whereas TNFalpha and the TNFalpha/IL10 ratio decreased. In logistic regression, IL10 (odds ratio (OR) 1.08, 95% confidence interval (CI) 1.01 to 1.16), monocyte count (OR 1.42, 95% CI 1.08 to 1.87) and National Institute for Health Stroke Survey score on admission (OR 1.17, 95% CI 1.05 to 1.31) were independent predictors of systemic infection. CONCLUSIONS: SAI is associated with stroke severity, excessive IL10-mediated response and an increased number of circulating monocytes. These results support the finding that acute ischaemic brain injury triggers a blood-borne anti-inflammatory response that decreases the antimicrobial drive of the immune system.