Modulation of monocyte matrix metalloproteinase-2 by breast adenocarcinoma cells

INTRODUCTION: The presence of monocyte and macrophage cells in growing breast tumors, and the positive relationship between the degree of immune cell infiltration and tumor growth, suggest a possible paracrine growth regulatory function of immune cells in breast cancer. METHOD: To better understand the interaction between monocytes and breast cancer cells, in vitro matrix metalloproteinase and tissue inhibitor of metalloproteinase activity was assessed from the THP-1 myeloid cell line in response to conditioned media from two breast cancer cell lines, MCF-7 and MDA-MB-231. RESULTS: Enzymography and immunoblotting revealed increased MMP-2 as well as increased levels of TIMP-1 and TIMP-2. Furthermore, a significant increase in the invasive potential of MCF-7 and MDA-MB-231 cells was noted in response to THP-1 cell-conditioned media. CONCLUSION: These data demonstrate that monocyte cells in the breast tumor microenvironment play an important role in the modulation of MMPs, which may have a significant effect on the control of tumor growth and metastatic spread

Chronic small vessel disease affects clinical outcome in patients with acute striatocapsular stroke

Background: Recovery from stroke is presumed to be a function of a cerebral network. Chronic small vessel disease (SVD) has been shown to disrupt this network’s integrity and has been proposed as a predictor of poor outcome after stroke. We studied this hypothesis in patients with acute ischemic stroke of the striatocapsular region, an area of pronounced cortical and subcortical connectivity. Methods: We identified 62 patients with isolated striatocapsular stroke from our stroke registry. The standardized workup included clinical rating according to the modified Rankin Scale (mRS) and MRI, rated according to the Fazekas scale for the extent of SVD, ranging from grade 0 to III. MRS at admission, at discharge, and a short-term recovery parameter (the difference between mRS at admission and discharge) were correlated with the extent of SVD. Comorbidity was assessed with the Charlson comorbidity index (CCI). Results: SVD was graded 0 in 7%, I in 60%, II in 18%, and III in 16% of patients. The median mRS at discharge for the groups was 2, 1, 2 and 4, and the median recovery parameter was 2, 1, 1 and 0.5, respectively. The extent of SVD significantly correlated with both the mRS at discharge and the recovery parameter. While age was also a significant predictor of these outcome parameters, SVD severity was a significant predictor even after correction for age or CCI. Conclusions: SVD is a predictor of poor outcome and recovery in striatocapsular stroke, independent of age or comorbidity. Severe SVD disturbs the integrity of the cerebral network leading to aggravation of and poor recovery from neurological deficits. Copyright (c) 2011 S. Karger AG, Base

Diffusion-weighted imaging for the differential diagnosis of disorders affecting the hippocampus

Background: The human hippocampus can be affected in a large variety of very different neurological diseases, of which acute ischemic stroke, transient global amnesia, epilepsy, and limbic encephalitis are the most common. Less frequent etiologies include various infections and encephalopathy of different origins. Clinical presentation notably comprises confusional state, altered vigilance, memory deficits of various extent and seizures. While in hypoxic or hypoglycemic encephalopathy, clinical presentation and surrounding circumstances provide some clues to reach the correct diagnosis, in the above-listed more common disorders, signs and symptoms might overlap, making the differential diagnosis difficult. This review presents recent studies using the diffusion-weighted imaging (DWI) technique in diseases involving the hippocampus. Methods: References for the review were identified through searches of PubMed from 1965 to January 2011. Only papers published in English were reviewed. Full articles were obtained and references were checked for additional material where appropriate. Results: All pathologies affecting the hippocampus are associated with distinct lesion patterns on magnetic resonance imaging, and especially DWI has the ability to demonstrate even minute and transient hippocampal lesions. In acute ischemic stroke in the posterior cerebral artery territory, involvement of the hippocampal formation occurs in four distinct patterns on DWI that can be easily differentiated and correspond to the known vascular anatomy of the hippocampus. In the subacute phase after transient global amnesia (TGA), dot-like hyperintense lesions are regularly found in the lateral aspect of the hippocampus on DWI. The DWI lesions described after prolonged seizures or status epilepticus include unilateral or bilateral hippocampal, thalamic, and cortical lesions of various extent, not restricted to vascular territories. In limbic encephalitis, DWI lesions are only infrequently found and usually affect the hippocampus, uncus and amygdala. Furthermore, in some rare cases DWI lesions of different etiology may coexist. Conclusion: In patients with diseases affecting the hippocampus, DWI appears to be useful in differentiating between underlying pathologies and may facilitate a definite diagnosis conducive to an optimal treatment. With a careful clinical examination, experience with the interpretation of DWI findings and knowledge of associated phenomena, it is indeed possible to differentiate between ischemic, ictal, metabolic, and TGA-associated findings. Copyright (C) 2011 S. Karger AG, Base

End-of-life decisions in acute stroke patients: an observational cohort study

Background: Crucial issues of modern stroke care include best practice end-of-life-decision (EOLD)-making procedures and the provision of high-quality palliative care for dying stroke patients. Methods: We retrospectively analyzed records of those patients who died over a 4-year period (2011–2014) on our Stroke Unit concerning EOLD, focusing on the factors that most probably guided decisions to induce limitation of life-sustaining therapy and subsequently end-of-life-care procedures thereafter. Results: Of all patients treated at our Stroke Unit, 120 (2.71 %) died. In 101 (86.3 %), a do-not-resuscitate-order (DNRO) was made during early treatment. A decision to withdraw/withhold further life supportive therapy was made in 40 patients (34.2 %) after a mean of 5.0 days (range 0–29). Overall patient death occurred after a mean time of 7.0 days (range 1–30) and 2.6 days after therapy restrictions. Disturbance of consciousness at presentation, dysphagia on day 1 and large supratentorial stroke were possible indicators of decisions to therapeutic withdrawing/withholding. Proceedings of EOL care in these patients were heterogeneous; in most cases monitoring (95 %), medical procedures (90 %), oral medication (88 %), parenteral nutrition (98 %) and antibiotic therapy (86 %) were either not ordered or withdrawn, however IV fluids were continued in all patients. Conclusions: A high percentage of stroke patients were rated as terminally ill and died in the course of caregiving. Disturbance of consciousness at presentation, dysphagia on day 1 and large supratentorial stroke facilitated decisions to change therapeutic goals thus initiating end-of-life-care. However, there is further need to foster research on this field in order to ameliorate outcome prognostication, to understand the dynamics of EOLD-making procedures and to educate staff to provide high-quality patient-centred palliative care in stroke medicine

Brain imaging in patients with transient ischemic attack: a comparison of computed tomography and magnetic resonance imaging

Background: Brain imaging in stroke aims at the detection of the relevant ischemic tissue pathology. Cranial computed tomography (CT) is frequently used in patients with transient ischemic attack (TIA) but no data is available on how it directly compares to magnetic resonance imaging (MRI). Methods: We compared detection of acute ischemic lesions on CT and MRI in 215 consecutive TIA patients who underwent brain imaging with either CT (n = 161) or MRI (n = 54). An MRI was performed within 24 h in all patients who had CT initially. Results: An initial assessment with CT revealed no acute pathology in 154 (95.7%) and possible acute infarction in 7 (4.3%) patients. The acute infarct on CT was confirmed by diffusion-weighted imaging (DWI) in only 2 cases (28.6%). DWI detected an acute infarct in 50 of the 154 patients with normal baseline CT (32.5%). Among 54 patients without baseline CT, DWI showed acute ischemic lesions in 19 (35.2%). The ischemic lesions had a median volume of 0.87 cm 3 (range: 0.08–15.61), and the lesion pattern provided clues to the underlying etiology in 13.7%. Conclusion: Acute MRI is advantageous over CT to confirm the probable ischemic nature and to identify the etiology in TIA patients

Extent of hypoattenuation on CT angiography source images in Basilar Artery occlusion: prognostic value in the Basilar Artery International Cooperation Study

<p><b>Background and Purpose:</b> The posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) quantifies the extent of early ischemic changes in the posterior circulation with a 10-point grading system. We hypothesized that pc-ASPECTS applied to CT angiography source images predicts functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS).</p> <p><b>Methods:</b> BASICS was a prospective, observational registry of consecutive patients with acute symptomatic basilar artery occlusion. Functional outcome was assessed at 1 month. We applied pc-ASPECTS to CT angiography source images of patients with CT angiography for confirmation of basilar artery occlusion. We calculated unadjusted and adjusted risk ratios (RRs) of pc-ASPECTS dichotomized at ≥8 versus <8. Primary outcome measure was favorable outcome (modified Rankin Scale scores 0–3). Secondary outcome measures were mortality and functional independence (modified Rankin Scale scores 0–2).</p> <p><b>Results:</b> Of 158 patients included, 78 patients had a CT angiography source images pc-ASPECTS ≥8. Patients with a pc-ASPECTS ≥8 more often had a favorable outcome than patients with a pc-ASPECTS <8 (crude RR, 1.7; 95% CI, 0.98–3.0). After adjustment for age, baseline National Institutes of Health Stroke Scale score, and thrombolysis, pc-ASPECTS ≥8 was not related to favorable outcome (RR, 1.3; 95% CI, 0.8–2.2), but it was related to reduced mortality (RR, 0.7; 95% CI, 0.5–0.98) and functional independence (RR, 2.0; 95% CI, 1.1–3.8). In post hoc analysis, pc-ASPECTS dichotomized at ≥6 versus <6 predicted a favorable outcome (adjusted RR, 3.1; 95% CI, 1.2–7.5).</p> <p><b>Conclusions:</b> pc-ASPECTS on CT angiography source images independently predicted death and functional independence at 1 month in the CT angiography subgroup of patients in the BASICS registry.</p&gt

Establishing an MSU service in a medium-sized German urban area — clinical and economic considerations

Background and purpose: Mobile stroke units (MSU) have been demonstrated to improve prehospital stroke care in metropolitan and rural regions. Due to geographical, social and structural idiosyncrasies of the German city of Mannheim, concepts of established MSU services are not directly applicable to the Mannheim initiative. The aim of the present analysis was to identify major determinants that need to be considered when initially setting up a local MSU service. Methods: Local stroke statistics from 2015 to 2021 were analyzed and circadian distribution of strokes and local incidence rates were calculated. MSU patient numbers and total program costs were estimated for varying operating modes, daytime coverage models, staffing configurations which included several resource sharing models with the hospital. Additional case-number simulations for expanded catchment areas were performed. Results: Median time of symptom onset of ischemic stroke patients was 1:00 p.m. 54.3% of all stroke patients were admitted during a 10-h time window on weekdays. Assuming that MSU is able to reach 53% of stroke patients, the average expected number of ischemic stroke patients admitted to MSU would be 0.64 in a 10-h shift each day, which could potentially be increased by expanding the MSU catchment area. Total estimated MSU costs amounted to € 815,087 per annum. Teleneurological assessment reduced overall costs by 11.7%. Conclusion: This analysis provides a framework of determinants and considerations to be addressed during the design process of a novel MSU program in order to balance stroke care improvements with the sustainable use of scarce resources

Clinical manifestations and immunomodulatory treatment experiences in psychiatric patients with suspected autoimmune encephalitis: a case series of 91 patients from Germany

Autoimmune encephalitis (AE) can rarely manifest as a predominantly psychiatric syndrome without overt neurological symptoms. This study’s aim was to characterize psychiatric patients with AE; therefore, anonymized data on patients with suspected AE with predominantly or isolated psychiatric syndromes were retrospectively collected. Patients with readily detectable neurological symptoms suggestive of AE (e.g., epileptic seizures) were excluded. Patients were classified as “probable psychiatric AE (pAE),” if well-characterized neuronal IgG autoantibodies were detected or “possible pAE” (e.g., with detection of nonclassical neuronal autoantibodies or compatible cerebrospinal fluid (CSF) changes). Of the 91 patients included, 21 (23%) fulfilled our criteria for probable (autoantibody-defined) pAE and 70 (77%) those for possible pAE. Among patients with probable pAE, 90% had anti-NMDA receptor (NMDA-R) autoantibodies. Overall, most patients suffered from paranoid-hallucinatory syndromes (53%). Patients with probable pAE suffered more often from disorientation (p < 0.001) and impaired memory (p = 0.001) than patients with possible pAE. Immunotherapies were performed in 69% of all cases, mostly with high-dose corticosteroids. Altogether, 93% of the patients with probable pAE and 80% of patients with possible pAE reportedly benefited from immunotherapies (p = 0.251). In summary, this explorative, cross-sectional evaluation confirms that autoantibody-associated AE syndromes can predominantly manifest as psychiatric syndromes, especially in anti-NMDA-R encephalitis. However, in three out of four patients, diagnosis of possible pAE was based on nonspecific findings (e.g., slight CSF pleocytosis), and well-characterized neuronal autoantibodies were absent. As such, the spectrum of psychiatric syndromes potentially responding to immunotherapies seems not to be limited to currently known autoantibody-associated AE. Further trials are needed