Subsyndromal delirium is associated with poor functional outcome after ischaemic stroke.

BACKGROUND AND PURPOSE: Subsyndromal delirium (SSD) refers to patients with delirious symptoms who do not meet the criteria for delirium. The aim was to determine the prognostic significance of SSD in stroke patients. METHODS: In all, 564 patients with ischaemic stroke (median age 71 years, 50.5% female) were included. The Confusion Assessment Method was used to assess symptoms of delirium and the Diagnostic and Statistical Manual of Mental Disorders, 5th edn, criteria were used to diagnose delirium. SSD was defined as one or more core features of delirium without fulfilling diagnostic criteria. Functional outcome was assessed using the modified Rankin Scale at 3 and 12 months after stroke. RESULTS: Delirium was diagnosed in 23.4% of patients and SSD in 10.3% of patients. SSD was associated with increased risk of poor functional outcome. The adjusted odds ratios (ORs) for unfavourable outcome at 3 and 12 months were 2.88 [95% confidence interval (CI) 1.43-5.79, P < 0.01] and 2.93 (95% CI 1.39-6.22, P < 0.01), respectively. In multivariate analysis, delirium was an independent predictor of poor functional outcome at 3 months (OR 6.41, 95% CI 3.36-12.21, P < 0.01) and 12 months (OR 6.11, 95% CI 3.05-12.27, P < 0.01) after stroke. Delirium was also independently associated with increased risk of death within 3 months (hazard ratio 3.68, 95% CI 1.69-8.02, P < 0.01) and 12 months (hazard ratio 3.76, 95% CI 2.05-6.90, P < 0.01). SSD was not associated with increased risk of death. CONCLUSIONS: In SSD patients the risk of poor functional outcome after stroke is increased and intermediate between patients with and patients without delirium.

The Effect of Repetitive Transcranial Magnetic Stimulation on Motor Symptoms in Hereditary Spastic Paraplegia.

Background: Hereditary spastic paraplegia (HSP) is a heterogeneous group of inherited disorders affecting predominantly the motor cortex and pyramidal tract, which results in slowly progressing gait disorders, as well as spasticity and weakness of lower extremities. Repetitive transcranial magnetic stimulation (rTMS) has been previously investigated as a therapeutic tool for similar motor deficits in a number of neurologic conditions. The aim of this randomized, controlled trial was to investigate the therapeutic potential of rTMS in various forms of HSP, including pure and complicated forms, as well as adrenomyeloneuropathy. Methods: We recruited 15 patients (five women and 10 men; mean age 43.7 ± 10.6 years) with the mentioned forms of HSP. The intervention included five sessions of bilateral 10 Hz rTMS over primary motor areas of the muscles of lower extremities and five sessions of similar sham stimulation. Results: One patient dropped out due to seizure, and 14 patients completed the study protocol. After real stimulation, the strength of the proximal and distal muscles of lower extremities increased, and the spasticity of the proximal muscles decreased. Change in spasticity was still present during follow-up assessment. No effect was observed regarding gait velocity. No changes were seen after sham stimulation. A post hoc analysis revealed an inverse relation between motor threshold and the change of the strength after active rTMS. Conclusions: rTMS may have potential in improving weakness and spasticity of lower extremities in HSP, especially of proximal muscles whose motor areas are located more superficially. This trial is registered with Clinicaltrials.gov NCT03627416.

Polymorphism in the chemokine receptor 7 gene (CCR7) is associated with previous myocardial infarction in patients undergoing elective coronary angiography.

Coronary artery disease (CAD) remains a major cause of death in developed countries. Both environmental and, less known, genetic factors contribute to progression of CAD to myocardial infarction (MI). Immune system is activated in patients with CAD through dendritic cells (DCs), which present plaque antigens to T lymphocytes. Production of proinflammatory cytokines by activated T cells contributes to plaque rupture in MI. Chemokine receptor 7 (CCR7) on DCs is required for their chemotaxis from plaque to lymph nodes. This makes possible an interaction of DCs with T lymphocytes and initiation of specific immune response. We hypothesized that single nucleotide polymorphisms (SNPs) in CCR7 gene locus are associated with previous MI in patients with CAD. To test this hypothesis, we genotyped six SNPs from the CCR7 gene locus in 300 consecutive patients, admitted for elective coronary angiography. We performed univariate-, multivariate- (including potential confounders) and haplotype-based tests of association of SNPs with previous MI and results of angiography. Allele A of rs17708087 SNP was associated with previous MI. This association remained significant after adjustment for age, sex, smoking, hypercholesterolaemia and drugs used by patients (odds ratio 2.13, 95% confidence interval: 1.13-3.86). Therefore, we conclude that CCR7 gene locus harbours a polymorphism that modifies risk of MI in patients with CAD. Replication of this association could be sought in a prospective cohort of initially healthy individuals.

Chicago sky blue 6B exerts neuroprotective and anti-inflammatory effects on focal cerebral ischemia.

Brain ischemia is one of the leading causes of death and long-term disability worldwide. Cessation of the blood supply to the brain directly stimulates many pathological events, including glutamate overload and neuroinflammation. Glial cell activation occurs shortly after ischemia onset, resulting in the release of proinflammatory cytokines and exacerbation of the detrimental effects of neuroinflammation. Proinflammatory signals influence the infiltration of a wide range of immune cells, including neutrophils, T cells and monocytes/macrophages. In this study, we aimed to verify the potential anti-inflammatory effect of Chicago Sky Blue 6B (CSB6B) in a rat model of focal cerebral ischemia (90-minute middle cerebral artery occlusion). CSB6B was administered 2 h before (pretreatment) or 1.5 h after reperfusion onset (posttreatment). A model of ischemic preconditioning was used as the comparator to pretreatment with CSB6B. The results of indicated that posttreatment with CSB6B had profound anti-inflammatory effects that were associated with reduced neurological deficits and a decreased infarct volume. At 24 h, 3 days and 7 days after brain ischemia, CSB6B administration reduced the protein levels of proinflammatory cytokines, such as Il1ß, Il6, Il18 and TNFα, in the cerebral cortex and the dorsal striatum. Treatment with CSB6B also limited the scope of microglia and astrocyte activation and the infiltration of immune cells. Taken together, this study shows that compounds such as CSB6B might be promising pharmacological tools; however, further studies on the improvements in the drug-like properties of these compounds must be undertaken.

Interleukin 6-174G>C polymorphism and risk of aneurysmal subarachnoid hemorrhage: case-control study and meta-analysis.

OBJECTIVES: Vascular inflammation contributes to the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH). Interleukin 6 (IL6) is a proinflammatory cytokine involved in many vascular pathologies. Two studies analyzing an association of the functional IL6 gene -174G>C promoter polymorphism with aSAH provided inconsistent results. The aim of this study was to investigate whether this IL6 polymorphism is associated with aSAH in a Polish population. MATERIAL AND METHODS: We genotyped 276 aSAH patients and 581 unrelated control subjects. All were of Caucasian origin. In addition, a meta-analysis combining results of the current and previously published studies was conducted. RESULTS: The distribution of IL6 genotypes and alleles did not differ significantly between aSAH (GG - 29.7%, GC - 50.0%, CC - 20.2%, G - 54.7%) and control subjects (GG - 32.0%, GC - 47.3%, CC - 20.7%, G - 44.3%). In the meta-analysis, the IL6-174G>C polymorphism was not associated with aSAH risk either. CONCLUSIONS: We failed to find an association between the IL6 -174G>C polymorphism and aSAH in analyzed European populations.

Association between hyperglycemia, heart failure and mortality in stroke patients.

BACKGROUND: Acute hyperglycemia predicts increased mortality after stroke. The aim of our study was to determine if acute stroke patients with hyperglycemia suffer from increased rate of in-hospital adverse events which could influence survival such as pneumonia, heart failure and myocardial infarction. METHODS: In a retrospective study with prospective follow-up, 689 patients with first-ever ischaemic stroke and high frequency of cardiovascular diseases were eligible. Follow-up period was 1-7 years (14 308 person-months). RESULTS: The frequency of in-hospital heart failure and nosocomial pneumonia was the highest in patients without pre-hospital diagnosis of diabetes mellitus and with fasting glucose >or=7 mmol/l (50% and 20.2%, respectively) and the lowest in patients without pre-hospital diagnosis of diabetes and fasting glucose

Immobilization of calcium sulfate contained in demolition waste.

This paper presents the results of a laboratory study undertaken to examine the treatment of demolition waste containing calcium sulfate by means of calcium sulfoaluminate clinker (CSA). The quantity of CSA necessary to entirely consume calcium sulfate was determined. Using infrared spectrometry analysis and X-ray diffraction, it was shown that calcium sulfate was entirely consumed when the ratio between CSA and calcium sulfate was 4. Standard sand was polluted by 4% calcium sulfate. Two solutions were investigated: *either global treatment of sand by CSA, *or immobilization of calcium sulfate by CSA, followed by the introduction of this milled mixture in standard sand. Regardless of the type of treatment, swelling was almost stabilized after 28 days of immersion in water.

Valorization of phosphogypsum as hydraulic binder.

Phosphogypsum (calcium sulfate) is a naturally occurring part of the process of creating phosphoric acid (H(3)PO(4)), an essential component of many modern fertilizers. For every tonne of phosphoric acid made, from the reaction of phosphate rock with acid, commonly sulfuric acid, about 3t of phosphogypsum are created. There are three options for managing phosphogypsum: (i) disposal or dumping, (ii) stacking, (iii) use-in, for example, agriculture, construction, or landfill. This paper presents the valorization of two Tunisian phosphogypsums (referred as G and S) in calcium sulfoaluminate cement in the following proportions: 70% phosphogypsum-30% calcium sulfoaluminate clinker. The use of sample G leads to the production of a hydraulic binder which means that it is not destroyed when immersed in water. The binder including sample S performs very well when cured in air but is not resistant in water. Formation of massive ettringite in a rigid body leads to cracking and strength loss.

Quantitative detection of Lactarius deliciosus extraradical soil mycelium by real-time PCR and its application in the study of fungal persistence and interspecific competition.

Real-Time PCR has been applied to quantify extraradical soil mycelium of the edible ectomycorrhizal fungus Lactarius deliciosus in an interspecific competition experiment under greenhouse conditions. Couples of Pinus pinea seedlings inoculated with either L. deliciosus, Rhizopogon roseolus, or non-inoculated (control) were transplanted into pots filled with two types of soil in all the possible combinations. Total DNA was extracted from soil samples at 3 and 6 months after transplantation to perform real-time PCR analysis. DNA extractions from soil mixed with known amounts of mycelium of L. deliciosus were used as standards. Six months after transplantation, the percentage of mycorrhizas of L. deliciosus and seedling growth were significantly affected by the soil type. Extraradical soil mycelium of L. deliciosus was positively correlated with the final percentage of mycorrhizas and significantly affected by the sampling time and soil depth. The competition effect of R. roseolus was not significant for any of the measured parameters, probably due to the sharp decrease of the mycorrhizal colonization by this fungus. We conclude that real-time PCR is a powerful technique for extraradical mycelium quantification in studies aimed at evaluating the persistence of introduced strains of L. deliciosus in field plantations.

Hypoalbuminemia in acute ischemic stroke patients: frequency and correlates.

OBJECTIVE: Hypoalbuminemia in acute stroke patients is associated with increased mortality and morbidity. The aim of our study was to determine the frequency and correlates of hypoalbuminemia in unselected cohort of patients with acute cerebral infarction. DESIGN: Prospective study. SETTING: University hospital. SUBJECTS: Seven hundred and five consecutive ischemic stroke patients. METHODS: Albumin and other serum protein fractions were measured within 36 h after stroke using electrophoresis. RESULTS: Hypoalbuminemia defined as serum albumin level <35 g/l was found in 45.5% of patients. Serum albumin level correlates significantly with age (r=-0.13, P<0.01), Scandinavian Stroke Scale score (r=0.14, P<0.01), body temperature on admission (r=0.14, P<0.01), leukocyte count (r=-0.17, P<0.01), fasting glucose (r=-0.16, P<0.01), total cholesterol (r=0.14, P<0.01), alpha1-globulin (r=-0.48, P<0.01), alpha2-globulin (r=-0.49, P<0.01), beta-globulin (r=-0.26, P<0.01) and gamma-globulin (r=-0.35, P<0.01). CONCLUSIONS: Hypoalbuminemia is a frequent finding in acute stroke patients and it is associated with more severe stroke and pro-inflammatory pattern of serum protein electrophoresis.

Use of sulfoaluminate cement and bottom ash in the solidification/stabilization of galvanic sludge.

Solidification/stabilization (S/S) process can improve the physical characteristics of wastes, reduce their leaching and limit the solubility of their heavy metals. The identification of binders able to assume the fixation of contaminants is essential for the success of the technique. In this study, calcium sulfoaluminate cement was added to another waste, bottom ash, in order to treat galvanic sludge. The properties of the resultant solid matrix (MS) were determined: setting time, compressive strength and products of hydration. Solid matrix composed of 77% waste and only 23% cement presented initial setting time lower than 4 h and 28 day-strength of 6 MPa. SEM investigations showed that contaminants present in the galvanic sludge (Cr) were encapsulated in the hydrated phases and particles of bottom ash.

Transscleral resection without hypotensive anaesthesia vs iodine-125 plaque brachytherapy in the treatment of choroidal melanoma.

AimsThe aim of this study was to compare transscleral resection technique performed without hypotensive anaesthesia (TSRWH) with iodine-125 brachytherapy (IBT) in the treatment of choroidal melanoma.Patients and methodsThis was a retrospective surgical cohort study. Nineteen eyes treated with TSRWH were matched with 53 eyes treated with IBT according to: tumour size, distance to fovea, distance to optic nerve, and follow-up time. Best-corrected visual acuity (BCVA), local recurrence, secondary enucleation, metastasis, overall and specific survival, and complications were evaluated.ResultsPatients treated with TSRWH had significantly better BCVA than those treated with IBT. The local recurrence risk was significantly higher when ciliary body was involved (HR=11.4, 95% CI 2.24-49.7, P=0.04). Metastatic disease was observed in 14 of 53 patients (26.4%) in the IBT group vs 3 patients (15.8%) in the TSRWH group (P=0.531). Multivariate analysis showed that iris involvement (HR=16.0, 95% CI 4.2-170.2, P=0.033) and large tumour (HR=2.3, 95% CI 1.2-4.8, P=0.04) increased the probability of metastasis. During follow-up, six patients (11.3%) in IBT group died vs two (10.5%) in the TSRWH group (P≥0.999). Nine patients required secondary enucleation: 5 (9.4%) in the IBT group vs 4 (21.1%) in the TSRWH group (P=0.231). The most common complications in IBT group were radiation-induced retinopathy (45.3%), neovascular glaucoma (28.3%), and macular oedema (24.5%), whereas rhegmatogenous retinal detachment (21.1%), ocular hypertension (21.1%), and submacular haemorrhage (15.8%) were the most frequent complications after TSRWH.ConclusionTSRWH is a technically challenging procedure. However, when performed successfully, this technique achieves better preservation of visual acuity than IBT and without the limitations inherent in hypotensive anaesthesia.

External beam irradiation plus (192)Ir implant after breast-preserving surgery in women with early breast cancer.

PURPOSE: To provide more information for the clinician and to analyze the impact of the boost with brachytherapy on the local disease-free survival (LDFS), disease-free survival (DFS), specific overall survival (OS), and cosmesis, a retrospective study of external radiation therapy and (192)Ir implantation in early breast cancer at Institut Català d'Oncologia has been undertaken. PATIENTS AND METHODS: From 1986 to 1996, 530 patients were selected for this study with a median follow-up period of 39.5 months (range, 10-115 months). External radiation therapy (combined with brachytherapy) was administered postoperatively to the breast in all patients. Mean given dose was 48.7 Gy (range, 42-52 Gy) with external radiation therapy to the breast, and 16.8 Gy (range, 10-27 Gy) was the mean dose with brachytherapy. Variables have been tested for cosmesis. Univariate and multivariate analysis have also been carried out. RESULTS: Mean age of the patients was 54 years (range, 28-81 years). Stages were distributed as follows: 350 patients (66%) in Stage I, 173 in Stage II (32.8%), and 7 in Stage III (1.1%). Pathologic distribution was 445 patients with infiltrating ductal carcinoma (84%), 20 patients with infiltrating lobular carcinoma (4%), and 65 patients (12%) of a miscellaneous group. OS for the entire group was 89.4% and 85.9% at 5 and 7 years respectively. Probability of DFS was 81.7% and 70.1% at 5 and 7 years. The LDFS was 94.9% and 91.7% at 5 and 7 years. The MFS probability was 85.5% and 76.9% at 5 and 7 years, respectively. Univariate analysis demonstrated that age (older than 52 years), premenopausal status, moderate and high histologic grades (Grades II-III), and presence of intraductal comedocarcinoma were prognostic factors for local relapse. Multivariate analysis for local disease-free survival demonstrated that only perineural or muscular infiltration remain as prognostic factors. Tumor dose bed of 70 Gy or higher had a negative impact in breast subcutaneous fibrosis, whereas dose rate lower than 65 cGy/h was better for skin color at 2 years. CONCLUSION: We conclude that patients with early-stage breast cancer undergoing external radiotherapy and LDR brachytherapy can be effectively managed. Overall survival, long-term local control, and cosmetic control are excellent.

Induction chemotherapy with cisplatin, bleomycin and methotrexate in advanced head and neck cancer--lack of therapeutic gain.

Seventy patients with stage IV head and neck cancer were treated by two courses of induction chemotherapy followed by surgery plus postoperative irradiation (7) or radical radiotherapy (62). One patient renounced to further treatment after chemotherapy. Each chemotherapy course consisted of methotrexate (40 mg/m2 days 1 and 14), bleomycin (10 mg/m2 days 1, 7 and 14), and cisplatin (50 mg/m2 day 4). Three patients did not complete the two courses of chemotherapy planned due to bad tolerance whereas the rest of the patients tolerated chemotherapy well. 2 CR (3%) and 35 PR (50%) were achieved for an overall response rate to chemotherapy of 53%. 35 (50%) CR were achieved with the whole treatment schedule. The 5-year disease-free survival is 26% for the whole group of patients. The prior response to chemotherapy neither influenced the complete responses to treatment nor the relapse-free survival. The addition of this chemotherapy to conventional treatment was of no value.

Transient hyperglycemia in ischemic stroke patients.

The aim of the study was to investigate glucose derangement and its short- and long-term prognostic significance in nondiabetic ischemic stroke patients. The study involved 262 consecutive patients, mean age: 70.1+/-12.4 years, with a supratentorial ischemic stroke. The following data were collected: patients characteristics, risk factors, comorbidities, and stroke severity assessed by the Scandinavian Stroke Scale (SSS). Serum glucose levels were measured on admission, on the next, 2nd, 3rd, 5th, 7th and 14th day after stroke onset. The outcome measures on day 30 were mortality and capacity to perform daily activities: the Barthel Index and Rankin Scale. The 1-year survival was estimated by the Kaplan-Meier method. Cox proportional hazards regression was used to assess predictors of 1-year mortality in nondiabetics. Diabetes mellitus was found in 24.8% of patients and transient hyperglycemia in 36.3% of patients. Patients with transient hyperglycemia scored lower on SSS in the subsequent days of assessment than patients with either diabetes mellitus or normoglycemia. They had larger ischemic lesions on computer tomography (CT) than diabetics and had higher 30-day mortality than normoglycemics (p<0.05). One-year mortality was similar in transient hyperglycemics and diabetics, and both were significantly higher than in normoglycemics (p<0.05). A proportional hazards model analysis showed that transient hyperglycemia is not an independent predictor of death within a year after stroke.

[Multicenter double-blind clinical trial comparing sucralfate vs placebo in the prevention of diarrhea secondary to pelvic irradiation]. / Ensayo clínico multicéntrico doble ciego comparativo de sucralfato y placebo en la prevención de la diarrea secundaria a irradiación pélvica.

BACKGROUND: Sucralfate has been used in the prophylaxis of acute enteric toxicity induced by radiation therapy of pelvic organs. The aim of the study was to demonstrate the efficacy of sucralfate in the prevention of the acute enteric toxicity induced by pelvic irradiation in cancer patients, compared with placebo, in a multicentric double-blind randomised clinical trial. PATIENTS AND METHOD: One hundred and twenty patients, with a localised pelvic cancer, 18 to 80 years old, with a Karnofsky index of 80% or more, and "normal" defecation habits (3-10 defecations/week), undergoing whole pelvic irradiation, were included. The duration of the study was 7 weeks, with weekly controls. The first week all patients received placebo. In the second week the patients were randomised into two groups: sucralfate (61 patients, 2 g/tid p.o. before meals) and placebo (59 patients). Radiotherapy started at the beginning of the third week and lasted until the end of the study. All patients received 45-50 Gy total dose (1.8-2 Gy/day, 5 days/week) with the "box technique". The main variables were the number of stools per week and the number of loperamide pills per week. RESULTS: The number of stools per week showed no differences between groups. By the contrary in the group intention to treat (120 patients) and per protocol (100 cases) the percentage of diarrhoeal stools per week showed a statistical significance in favour of sucralfate: (p < 0.05) and (p < 0.03) respectively, concerning the evolution of this variable from the baseline (first week) to the end of the pelvic radiotherapy (seventh week). Furthermore, the consumption of loperamide was significantly lower in the sucralfate group (p < 0.001). CONCLUSION: Sucralfate is effective in the preparation of acute enteric toxicity induced by pelvic irradiation.

[Prostatic brachytherapy indications and technique]. / Indicaciones y técnica de la braquiterapia prostática.

Prostate cancer is an important health problem, mainly in elderly men. It is the second cause of death among men in USA ant the third at the "Registro del Cáncer de Tarragona", behind both the lung and colorectal cancer. About the 58% of the newly diagnosed cancers are localized, therefore, they have to be treated with curative intention. Radical prostatectomy is considered the gold standard treatment for organ confined prostate cancer in our country. On basis to the experience of American groups and the improvement of both, image techniques and dosimetric calculation, brachytherapy has been brought in as a new option in the treatment of localized prostate cancer. We started our program of brachytherapy for prostate cancer on May 2000. We have performed 51 procedures by now. Our protocol and the technique to perform a prostatic brachytherapy are described following.

[Prognostic significance of early CT changes in ischemic stroke patients]. / Prognostyczne znaczenie wczesnych zmian w tomografii komputerowej glowy u chorych z udarem niedokrwiennym mózgu.

The aim of the study was to establish the prognostic value of early CT findings in predicting the 30-day mortality after stroke, to assess the prevalence of these findings in acute stroke patients, and to examine the correlation between these findings and the clinical status. 134 patients (mean age 67.5 +/- 12.1) with supratentorial ischaemic stroke and CT performed within 12 hours from onset of the symptoms were included into the study. The neurological deficit and consciousness disturbances were assessed by means of Scandinavian Stroke Scale. The 30-day mortality was registered. CT findings were found in 84 (63.7%) patients, including hypodense lesions in 74 (55.5%), mass effect in 55 (41.0%) and hyperdense middle cerebral artery sign in 5 (3.7%) cases. Patients with mass effect had greater neurological deficit on admission (p < 0.0001), more frequently developed disorders consciousness (p = 0.001) and had greater 30-day mortality (p < 0.0001). Patients with hypodense lesions of at least two types presented with greater neurological deficit observed on the second day of hospitalization (p < 0.05) and had also greater 30-day mortality (p = 0.01). On multivariate analysis mass effect seen in early CT, as well as older age and greater neurological deficit appeared to be independent predictors of 30-day mortality.