Incidence of orolingual angioedema after intravenous thrombolysis for stroke.

INTRODUCTION: Orolingual angioedema (OA) is a known adverse effect of intravenous (i.v.) alteplase. We analyzed all patients treated with i.v. alteplase for stroke at our hospital since approval of i.v. thrombolysis in Italy in 2004 to assess the incidence of this complication. PATIENTS AND RESULTS: Four hundred thirty-three patients received alteplase for stroke from April 2004 to May 2017. Two women developed OA (0.4%; 95% confidence interval 0.1 to 1.6%). Angioedema was mild in one case and severe in the other, with massive swelling of the lips, tongue, and oropharyngeal mucosa, and oropharyngeal bleeding, requiring intubation. Neither patient used ACE-inhibitors. DISCUSSION: The incidence of orolingual angioedema was very low in our series. Although OA is usually mild, anaphylactoid reactions may rarely occur, because of the variable degree of activation of the complement system and kinin cascade caused by alteplase. In such instances, admission to neurointensive care may be required. Specific bradykinin antagonists or drugs that target the kallikrein-kinin system are beginning to be used in the more severe cases. Thus, doctors and nurses caring for acute stroke patients need to be able to recognize and treat this complication.

Modulation of macrophage phenotype and protein secretion via heparin-IL-4 functionalized supramolecular elastomers.

Hallmark of the in situ tissue engineering approach is the use of bioresorbable, synthetic, acellular scaffolds, which are designed to modulate the inflammatory response and actively trigger tissue regeneration by the body itself at the site of implantation. Much research is devoted to the design of synthetic materials modulating the polarization of macrophages, which are essential mediators of the early stages of the inflammatory response. Here, we present a novel method for the functionalization of elastomers based on synthetic peptide chemistry, supramolecular self-assembly, and immobilization of heparin and interleukin 4 (IL-4), which is known to skew the polarization of macrophages into the wound healing "M2" phenotype. Ureido-pyrimidinone (UPy)-modified chain extended polycaprolactone (CE-UPy-PCL) was mixed with a UPy-modified heparin binding peptide (UPy-HBP) to allow for immobilization of heparin, and further functionalization with IL-4 via its heparin binding domain. As a first proof of principle, CE-UPy-PCL and UPy-HBP were premixed in solution, dropcast and exposed to primary human monocyte-derived macrophages, in the presence or absence of IL-4-heparin functionalization. It was demonstrated that the supramolecular IL-4-heparin functionalization effectively promoted macrophage polarization into an anti-inflammatory phenotype, in terms of morphology, immunohistochemistry and cytokine secretion. Moreover, the supramolecular functionalization approach used was successfully translated to 3D electrospun scaffolds for in situ tissue engineering purposes, where UPy-HBP retention, and heparin and IL-4 attachment to the supramolecular scaffolds were proven over 7 days. Lastly, human monocyte-derived macrophages were cultured on 3D scaffolds, which, in case of IL-4-heparin functionalization, were proven to promote of an anti-inflammatory environment on protein level. This study presents a novel method in designing a versatile class of functionalized elastomers that effectively harness the anti-inflammatory behavior of macrophages in vitro, and as such, may be instrumental for the development of a new class of synthetic materials for in situ tissue engineering purposes. STATEMENT OF SIGNIFICANCE: Macrophages and their phenotypic and functional plasticity play a pivotal role in metabolic homeostasis and tissue repair. Based on this notion, bioactivated materials modulating macrophage polarization were extensively investigated in the past. Here, we designed immunomodulating, synthetic materials based on supramolecular immobilization of a heparin binding peptide, and further bioactivation with heparin and IL-4, an anti-inflammatory cytokine responsible for M2 activation and polarization. Human monocyte-derived macrophages cultured on heparin-IL-4 bioactivated materials displayed an elongated morphology and an anti-inflammatory phenotype, with downregulation of pro-inflammatory cytokines and promotion of anti-inflammatory cytokines over time. This study represents the first step in designing a novel class of synthetic, bioactivated materials that harness the regenerative behavior of host macrophages towards in situ tissue regeneration.

Ethical issues in end of life treatments for patients with dementia.

Dementia is a terminal disease, associated with great suffering and difficult decisions in the severe stage. The decision-making process is characterized by uncertainty because of lack of scientific evidence in treatments and by the need to reconcile conflicting points of view. In intercurrent diseases, aggressive interventions are used without consideration of its futility; in comparison with cancer, several consequences of physicians' attitude not to consider dementia as a terminal disease have been reported, especially concerning pain relief. Lack of evidence of artificial nutrition and hydration effectiveness makes advance care planning relevant.

Ethical questions in the treatment of subjects with dementia. Part I. Respecting autonomy: awareness, competence and behavioural disorders.

The document deals with some ethical issues raised by the treatment of demented people. In particular the conceptual and empirical aspects of the assessment of awareness and competence of these patients are analysed, as well as the dilemmas related to the treatment of behavioral disorders.

Thrombolysis for acute ischemic stroke: the problem of consent.

The physician who decides to administer a thrombolytic therapy to a patient with acute stroke, has to consider both the results of randomized controlled trials, a complex matter itself, and problems related to consent, with its deontological and legal aspects, in the difficult contest of the emergency situations and acute stroke care. Although the analysis of studies on thrombolysis in medical literature has been ample and may be redundant, the latter aspect, i.e. that of how to cope with the problem of consent, has never been treated adequately. The problem of consent is particularly important and delicate in Italy and in most countries of the European Union, where thrombolytic therapy can be used only off label or within experimental studies. This document aims to provide the tools needed to overcome the gap between the generic indication for thrombolytic therapy in acute stroke, coming from clinical studies, and its effective use.

Superficial siderosis of the central nervous system after brachial plexus injury. Case report.

Superficial siderosis is a rare condition characterized by deposition of hemosiderin in the leptomeninges and in the subpial layers of the brain and spinal cord. It is associated with cerebrospinal fluid abnormalities consistent with recurrent bleeding into the subarachnoid space. The usual symptoms are hearing loss, ataxia, spastic paraparesis, sensory and sphincter deficits, and mental deterioration. A case is presented of severe superficial siderosis of the central nervous system in a 51-year-old man who had suffered a brachial plexus injury at the age of 20 years. The diagnosis was made by means of magnetic resonance imaging 16 years after the initial symptoms, which comprised bilateral hearing loss and anosmia. Subarachnoid bleeding was due to traumatic pseudomeningocele of the brachial plexus, a very unusual cause of superficial siderosis. This case is interesting insofar as the surgical treatment prevented further bleeding and possibly progression of the disease.

Different patterns of dissociation in unilateral spatial neglect.

The aim of this paper is to discuss the issue of dissociations found in unilateral spatial neglect according to the modality of space exploration and the nature of the task. For this purpose we present a reanalysis of the data from a recent paper of Gentilini et al. (1989) comparing visual and blindfolded exploration of a computer keyboard and discuss the performance of a left-brain-damaged patient with right visuospatial neglect and left-sided neglect dyslexia. We conclude that unilateral spatial neglect cannot be interpreted as a disruption of a single attentional mechanism, but rather it reflects impaired attentional mechanisms at several levels of cognitive processing.

VEP and EEG in cortical blindness: a case with a complicated course.

We report a case of cortical blindness secondary to an extensive bilateral occipital ischemic infarct and complicated by the onset of bilateral optic nerve ischemia. We discuss the behavior of the VEP, present--an unusual finding--in the first phase of the occipital ischemic lesion, and the value of the alpha band rhythm in the EEG record.

[Lupus anticoagulant antibody (LAC) and juvenile cerebral ischemic attack: a clinical case]. / Anticorpo anticoagulante lupus (LAC) e ictus ischemico cerebrale giovanile: un contributo clinico.

The lupus anticoagulant (LAC) is an acquired circulating serum immunoglobulin that prolongs all phospholipid-dependent coagulation tests. It has been recently associated with focal cerebral ischemia. We present here a case of LAC associated multiple cerebral ischemic events in a young adult and discuss laboratory criteria for a reliable diagnosis. In order to detect the presence of LAC, both the activated partial thromboplastin time (PTT), the kaolin clotting time (Exner assay) and the tissue thromboplastin inhibition assay (Schleider assay) should be evaluated. We conclude that LAC should be looked for in all young stroke patients with otherwise unexplained cerebral infarctions.

Three-year neuropsychological follow-up of patients with reversible ischemic attacks.

A short neuropsychological test battery designed to measure language, memory and visuospatial abilities was administered to 217 patients with reversible ischemic attacks. Patients were tested twice: the first time more than one month, but less than one year, from the last ischemic episode, and the second time three years later. A comparison between the first and the second testing session did not disclose any significant worsening. The degree of atherosclerosis and the occurrence of further ischemic episodes during the follow-up period were found to be unrelated to change in performance at the test battery. These results seems to challenge the hypothesis that multi-infarct dementia may follow apparently reversible, or even clinically silent, ischemic episodes.

[Licorice-induced myopathy. Report of a new case]. / Miopatia da liquerizia. Presentazione di un nuovo caso.

A 64 year-old man, who had been ingesting 20 g of licorice daily for about five months, developed a progressive, diffuse muscle weakness, with myoglobinuria, severe hypokalemia and elevated serum muscle enzymes. Electromyography and muscle biopsy results were consistent with a necrotizing myopathy. Following licorice withdrawal and appropriate electrolyte administration, complete clinical recovery was observed within about ten days. Previous reports of similar cases are reviewed and causative factors of this kind of myopathy are discussed.