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Ethnopharmacological Relevance: Lippia lacunosa Mart. & Schauer is an endemic plant from the Serra do Espinhaço mountain range located on the Atlantic plateau, Brazil. It is known as "chá de pedestre" and "rosmaninho" in folk medicine. This species has a characteristic mango aroma and is widely used by the population for flu, colds, sinus infections, coughing, relaxing baths, and foot baths after long walks. It is often confused with and, therefore, used interchangeably with L. rotundifolia and L. pseudothea., Aim of the Study: This study aimed to increase scientific knowledge on the ethnopharmacological use of Lippia lacunosa through the evaluation of the micromolecular composition and anti-inflammatory and antinociceptive activities of the hexane and ethanolic extracts, essential oil, and fractions in mice., Materials and Methods: The chemical profile of L. lacunosa extracts and fractions were obtained by chromatographic methods such as Ultra-Performance Liquid Chromatography (UPLC), Gas Chromatography (GC), Column Chromatography (CC), and Thin Layer Chromatography (TLC). Carrageenan-induced paw edema was used to investigate the anti-inflammatory activity in mice. Mechanical allodynia induced by carrageenan and hot plate tests were employed to evaluate the antinociceptive activity., Results: The main constituents found in the essential oil were the monoterpenes myrcene (13.81%), linalool (6.84%), ipsenone (21.2%), and myrcenone (25.44%); and sesquiterpenes elemol (7.30%) and spathulenol (3.15%). The chromatograph fractionation of essential oil yielded a fraction rich in the main compounds (F33), ipsenone and mircenone. In experimental models of paw edema and mechanical allodynia induced by carrageenan (600 μg, 30 μL, i.pl.), the administration of hexane extract, essential oil (50 or 100 mg/kg, p.o.) or majority fraction (10 mg/kg, p.o.) reduced paw edema. The ethanolic extract (100 mg/kg) reduced mechanical allodynia only in the 2 nd h of evaluation. On the other hand, the hexane extract (50 or 100 mg/kg) and essential oil (100 mg/kg), as well as the majority fraction (10 mg/kg), reduced mechanical allodynia throughout the evaluation period. The hexane extract, essential oil, and majority fraction F33 also reduced the heat-induced nociceptive response. Also, majority fraction F33 did not affect the time mice spent in the rota-rod apparatus., Conclusions: The elucidation of the composition of the essential oil and the demonstration of the activity of L. lacunosa in experimental models of acute inflammation and also in models of nociceptive and inflammatory pain can help to increase knowledge on the ancient ethnopharmacological use by the Bandeirantes, aiming at the evaluation of the species as a candidate for herbal medicine or phytopharmaceutical in the treatment of patients with inflammatory and painful conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Lumbar musculature has a fundamental role in spine stability and spinal balance. Muscle atrophy and fat infiltration play an important role in pain pathophysiology. Accordingly, the preoperative condition of lumbar muscles may influence clinical outcomes after surgical treatment. In this context, the aim of this study was to evaluate the association between preoperative lumbar paravertebral muscle fat infiltration and clinical outcomes after lumbar interbody fusion., Methods: A retrospective study of patients with lumbar pathology submitted to lumbar transforaminal (TLIF) or posterior interbody fusion (PLIF) was performed, with a minimum of two years of follow-up. Preoperative lumbar magnetic resonance imaging (MRI) images were classified for fat infiltration in lumbar multifidus muscle and correlated with clinical outcomes., Results: Seventy-five patients were included: 24 submitted to PLIF and 51 to TLIF. Most patients underwent surgery for spondylolisthesis (67%). Higher degrees of fat infiltration were associated with more advanced age (54.8 vs. 49.1 years old, p = 0.04) and more leg pain after surgery (p = 0.04). No statistically significant differences in other clinical outcomes such as Oswestry Disability Index, visual analogue scale for back and leg pain, self-reported back pain relief, return to work and overall satisfaction were found between different groups of fat infiltration. The improvement in leg pain was associated with improvement in self-reported lumbar pain (p < 0.001)., Conclusion: Age and preoperative degree of fat infiltration may be important to predict improvement in leg pain after lumbar interbody fusion. The absence of solid literature on this topic and universal assessment methodologies reinforce the need for further studies., (© 2022. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Ethnopharmacological Relevance: Lippia alba (Mill.) N.E.Br. ex Britton & P. Wilson is traditionally used in Brazil as an adjunct in the relief of mild anxiety, as an antispasmodic, and as an antidyspeptic. This medicinal species was included in the Phytotherapeutic Form of the Brazilian Pharmacopeia 2nd edition (2021) and has already been described as the most used medicinal plant in a study with patients from an Anticoagulation Clinic in Brazil. Meanwhile, no studies were found that support the safety of the use of L. alba in patients using anticoagulants, a drug with several safety limitations., Aim of the Study: Provide scientific evidence to ensure the safety of the concomitant use of L. alba and warfarin and support the management of these patients by evaluating its in vitro anticoagulant effect and chemical composition. And, as a timely complementation, evaluate the potential of this medicinal species in the development of new antithrombotics., Methods: The chemical profile of L. alba derivatives was analyzed by chromatographic methods such as Ultra-Performance Liquid Chromatography (UPLC) coupled with electrospray ionization mass spectrometry (ESI-MS), qualitative UPLC using Diode-Array Detection, and Thin Layer Chromatography. The anticoagulant activity was evaluated by the innovative Thrombin Generation Assay by Calibrated Automated Thrombogram method and using traditional coagulometric tests: prothrombin time, activated partial thromboplastin time, and plasma fibrinogen measurement., Results: Extracts and fractions prolonged the coagulation time in all the tests and reduced thrombin formation in thrombin generation assay. Coagulation times with the addition of ethanloic extract (2.26 mg/mL) was 17.78s, 46.43s and 14.25s respectively in prothrombin time, activated partial thromboplastin time and fibrinogren plasma measurement. In thrombin generation test, this same extract showed ETP as 323 nM/min compared to control (815 nM/min) with high tissue factor and 582 nM/min compared to control (1147 nM/min) using low tissue factor. Presence of flavonoids, phenylpropanoids, and triterpenes were confirmed by chromatographic methods and 13 compounds were identified by UPLC-ESI-MS. Based on these results and on the scientific literature, it is possible to propose that phenylpropanoids and flavonoids are related to the anticoagulant activity observed., Conclusion: The results demonstrate the in vitro anticoagulant activity of L. alba, probably due to the activation of intrinsic and extrinsic pathways. It is concluded, then, that there is a potential for interaction, which needs to be further studied, between L. alba and warfarin. Also, this medicinal species shows a great potential for use in the development of new antithrombotics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Costus spiralis (Jacq.). Roscoe (Costaceae) is traditionally used in Brazil for the treatment of kidney diseases such as pyelonephritis, urethra inflammation, kidney stones, and inflammatory conditions. There are reports of its use by Brazilian Indians since the 17th century when it was known as "pacocatinga." Currently, the use of the Costus species in Brazil is widespread, which was evidenced by the inclusion of the genus in the Brazilian National List of Medicinal Plants of Interest to the Unified Health System (RENISUS)., Aim of the Study: This study aimed to confirm the ethnopharmacological use of Costus spiralis in the treatment of kidney diseases, toxicity study using animal models, and the phytochemistry of the species., Materials and Methods: The chemical profile of Costus spiralis leaves extract (CSLE) was obtained for the hydroethanolic extract by ultra-performance liquid chromatography coupled to a mass spectrometer and ultraviolet detector with diode array (UPLC-UV/DAD-ESI-MS). The acute oral toxicity of the extract was predicted using the neutral red uptake cytotoxicity assay. Wistar rats were used in a model in vivo for confirmation of acute oral toxicity (2000 mg/kg p.o. for 14 days.) and determination of the effect on a cisplatin-induced nephrotoxicity model., Results: The analysis by UPLC-UV/DAD-ESI-MS showed that the chemical composition of the extract is mostly di-glycosylated flavones of apigenin. In the extract were identified the flavones vicenin II and schaftoside. The quantification of total flavonoids by spectrometry showed 0.880%. CSLE proved to be safe for acute oral administration (2000 mg/kg) with an IC 50 value of 222.9 μg/mL and predicted oral toxic dose of 523.82 μg/mL in a neutral red uptake cytotoxicity assay. The absence of death allows the classification of the extract in class 5 according to OECD 423 guidelines and therefore it can be considered as a high acute safety product, which is highly relevant, considering the wide popular use of the species. In the cisplatin-induced nephrotoxicity model, C. spiralis extract (5, 15, and 30 mg/kg) significantly improved renal function, reversing almost completely the effects on plasma creatinine levels and creatinine clearance (p < 0.001)., Conclusions: This study demonstrates that oral administration of Costus spiralis extract leaves is safe and effective in restoring the renal function in rats in a cisplatin-induced nephrotoxicity. It is suggested that the observed activity is related to the flavonoids present. This hypothesis should be confirmed, and the participation of other secondary metabolites should be investigated in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Citrus sinensis and Lippia alba are herbal medicines widely used in the form of tea (infusion, decoction), which ethanolic extracts have already shown great anticoagulant activity in vitro . For this reason, they seem to be excellent candidates for the development of new antithrombotics and also have the potential to interact with them. The aim of this study was to evaluate the activity of aqueous extracts in blood coagulation and platelet aggregation, in addition to analysing the micromolecular composition of these species. Thrombin generation test (TGT) by the Calibrated Automated Thrombogram method and Platelet Aggregation Test by turbidimetry were performed to evaluate the biological activities, while the chemical composition was qualitatively evaluated using high-performance liquid chromatography. Aqueous extracts were elaborated according to the folk use. All extracts were effective in reducing thrombin formation in TGT. Infusion of L. alba and infusion and decoction of C. sinensis at a concentration of 0.6 mg/ml significantly reduced platelet aggregation induced by ADP, and only the decoction of L. alba at the same concentration was able to significantly reduce collagen-induced platelet aggregation. The presence of phenylpropanoids and flavonoids in C. sinensis and L. alba extracts was verified. Furthermore, hesperidin was identified in C. sinensis through coinjection. C. sinensis and L. alba are rich in phenolics and demonstrated an in-vitro effect on important processes of haemostasis (blood coagulation, platelet agreggation), corroborating the potential of C. sinensis and L. alba for the development of antithrombotics and interact with them., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Gold nanorods (GNRs) are increasingly being studied for diagnostic and therapeutic purposes. Green synthesis based methods with natural compounds as additives stand out as a hope in terms of better synthesis methodology, with advantages of producing potentially less toxic and, perhaps, biologically active GNRs due to influence of natural additives used during synthesis. Exploring green chemistry using different natural phenolic compounds, the present work reveals different in vitro activity of GNRs evaluated against different parasites that causes skin infectious diseases compared to GNRs produced by convencional seed mediated method. This approach brings advantages in producing active GNRs, with ease calling, less cytotoxic and with a better selectivity index (SI) than GNRs synthesized by conventional seed mediated synthesis, opening new possibilities for therapies. Natural compounds used in green syntheses were gallic acid (GA), resveratrol (RSV) and a purified fraction of the hydroalcoholic extract of Stryphnodendron obovatum. GNRs exhibited great activity against Leishmania braziliensis, and the dermatophytes Tricophyton rubrum, T. interdigitale and Microsporum gypseum. The anti-Leishmania and antidermatophytic activity of GNRs reinforce the applicability of GNRs in biomedical field and the influence of synthesis method in biological activity, showing benefits related to the seedless synthesis with natural compounds. In addition, these preliminary results indicate the possibility of exploring at maximum the physical and chemical properties of GNRs in addition to the biological activity itself, such as the development of topical antiparasitic formulations for association with phototherapy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Apitherapy is a branch of traditional medicine that uses bee products to manage numerous diseases. In this context, the antiherpetic effect of these bee products has been demonstrated in some studies with some controversial results., Aim of the Study: Thus, we conducted a systematic review and meta-analysis to compare the effectiveness of honey and propolis with acyclovir, the reference drug, in the treatment of cold sores and genital herpes., Materials and Methods: The selection of eligible studies was conducted through the search in Pubmed/MEDLINE, Scopus, Cochrane Library, LILACS, and Electronic Scientific Library., Results: The search yielded 147 articles, of which nine were considered eligible for analysis. The analysis of these studies showed that the healing property of propolis is superior to that obtained for acyclovir (95% CI: 2.70 to 8.25; p = 0.0001). Furthermore, honey also presented a better healing effect than acyclovir against Herpes simplex virus-induced wounds (95% CI: 3.58 to -0.19; p = 0.03), inducing complete re-epithelization of herpetic lesions after 8 days, while for acyclovir, the healing time average was 9 days. It also provoked a similar reduction of pain caused by herpetic compared to acyclovir (95% CI: 2.27 to -0.42; p = 0.18)., Conclusions: Overall, these results confirm the use of honey and propolis as potent antiherpetic agents., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Since the publication of endovascular treatment trials and European Stroke Guidelines, Portugal has re-organized stroke healthcare. The nine centers performing endovascular treatment are not equally distributed within the country, which may lead to differential access to endovascular treatment. Our main aim was to perform a descriptive analysis of the main treatment metrics regarding endovascular treatment in mainland Portugal and its administrative districts., Material and Methods: A retrospective national multicentric cohort study was conducted, including all ischemic stroke patients treated with endovascular treatment in mainland Portugal over two years (July 2015 to June 2017). All endovascular treatment centers contributed to an anonymized database. Demographic, stroke-related and procedure-related variables were collected. Crude endovascular treatment rates were calculated per 100 000 inhabitants for mainland Portugal, and each district and endovascular treatment standardized ratios (indirect age-sex standardization) were also calculated. Patient time metrics were computed as the median time between stroke onset, first-door, and puncture., Results: A total of 1625 endovascular treatment procedures were registered. The endovascular treatment rate was 8.27/100 000 inhabitants/year. We found regional heterogeneity in endovascular treatment rates (1.58 to 16.53/100 000/year), with higher rates in districts closer to endovascular treatment centers. When analyzed by district, the median time from stroke onset to puncture ranged from 212 to 432 minutes, reflecting regional heterogeneity., Discussion: Overall endovascular treatment rates and procedural times in Portugal are comparable to other international registries. We found geographic heterogeneity, with lower endovascular treatment rates and longer onset-to-puncture time in southern and inner regions., Conclusion: The overall national rate of EVT in the first two years after the organization of EVT-capable centers is one of the highest among European countries, however, significant regional disparities were documented. Moreover, stroke-onset-to-first-door times and in-hospital procedural times in the EVT centers were comparable to those reported in the randomized controlled trials performed in high-volume tertiary hospitals.

Background: Red cell distribution width (RDW) has been associated with mortality and outcome in a wide variety of non-neurological and neurological diseases, namely in myocardial infarction and acute ischemic stroke, and the reason for this is not completely understood. We aimed to investigate RDW as a potential prognostic marker in patients with intracerebral hemorrhage (ICH)., Methods: This is a retrospective study of consecutive patients with acute non-traumatic ICH admitted to a single center during a 4-year period. We reviewed individual clinical records to collect demographic and baseline information, including RDW at admission, 3-month functional status, and incidence of death during follow-up. Baseline computed tomography imaging was reviewed to classify the location of ICH, and to measure ICH volume and perihematomal edema volume. Patients were divided according to quartile distribution of RDW (RDW-Q1-4)., Results: The final study population consisted of 358 patients, median age 71 years (interquartile range [IQR] 60-80), 55% were male, and median Glasgow Coma Scale was 14 (IQR 10-15), with a mean follow-up of 17.6 months. Patients with higher RDW values were older (p = 0.003), more frequently presented with an active malignancy (p = 0.005), atrial fibrillation (p < 0.001), intraventricular hemorrhage (p = 0.048), and were anticoagulated (p < 0.001). Three-month functional independence was similar throughout RDW quartiles. RDW-Q4 was independently associated with increased 30-day mortality (adjusted odds ratio = 3.36, 95%CI = 1.48-7.62, p = 0.004), but not independently associated with increased mortality after 30 days (adjusted hazards ratio = 0.71, 95%CI = 0.29-1.73, p = 0.448)., Conclusions: RDW is a robust and independent predictor of 30-day mortality in non-traumatic ICH patients, and further studies to understand this association are warranted.

Contrast-induced neurotoxicity (CIN) is an adverse reaction to contrast agents which can occur in the context of diagnostic and therapeutic neurological endovascular procedures. Our goal was to conduct a systematic review of patients reported in the literature diagnosed with CIN after neurological endovascular procedures. A systematic search of EMBASE and MEDLINE databases was conducted. Inclusion criteria were age ≥ 18 years; neurological endovascular procedure performed ≤ 24 h before ictus; new manifestations compatible with encephalic dysfunction; imaging performed < 7 days after ictus; exclusion of other causes and manifestations attributed to pre-existing conditions. Forty-eight patients were included, of which 60.4% were female and 60.4% had arterial hypertension; median age was 63 years. The most frequent procedure was diagnostic cerebral angiography (n = 24, 50.0%) and non-ionic contrast agents were more frequently used (n = 40, 83.3%). Twenty-six patients (54.2%) developed clinical manifestations compatible with CIN during or immediately after the procedure, and the most frequent manifestations were encephalopathy, cortical blindness and motor deficit. The most frequent imaging findings were cortical contrast enhancement on CT (n = 23/42), and cortical sulci effacement (n = 18/48). Most patients presented complete clinical recovery (89.6%) at a median time of 3 days. Among patients with neuroimaging changes who underwent follow-up, complete regression of the abnormalities was shown in 81.5% at a median time of 5 days. CIN is a rare adverse reaction in the context of neurological endovascular procedures. Recognition of clinical manifestations and typical imaging abnormalities, while excluding other causes, is essential for diagnosis.

We report the case of a patient with an anterior ischemic stroke due to tandem occlusion of the left M2 segment and ipsilateral internal carotid artery (ICA), with concomitant severe stenosis of the ipsilateral external carotid artery (ECA) and contralateral ICA, and moderate stenosis of the left vertebral artery (VA); as thrombectomy was not possible, stenting of the right ICA was performed. Two days after significant recovery, the patient showed neurological deterioration when in upright position, and brain magnetic resonance imaging confirmed decreased cerebral blood flow on the left hemisphere. Stenting of the left ECA and balloon angioplasty of the ipsilateral VA were performed in order to increase collateral flow, with an almost complete resolution of symptoms. This case highlights the importance of assessing the collateralization pattern when an ICA occlusion is present, and the potential need to revascularize an ipsilateral stenotic ECA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

: Evaluate the in-vitro effect of Mentha crispa extract on blood coagulation, compare the conventional coagulometric tests with thrombin generation test (TGT), and study the qualitative micromolecular composition of M. crispa. Extract of M. crispa was incubated with plasma and used in the coagulometric tests: prothrombin and activated partial thromboplastin times, fibrinogen, and TGT. A phytochemical prospection was performed to evaluate the chemical composition of this extract. The extract was efficient in prolonging prothrombin time and activated partial thromboplastin time, and reducing fibrinogen levels and TGT parameters, indicating that the extract of M. crispa inhibited the intrinsic and extrinsic pathways of blood coagulation. The results obtained in TGT are in agreement with the results of conventional coagulometric tests and the in-vitro anticoagulant activity of M. crispa suggests that its use by patients using oral anticoagulants deserves caution.

Objectives : The characterization of markers capable of predicting clinically significant hematoma growth (HG) in patients with intracerebral hemorrhage (ICH) may be useful for the selection of patients for clinical trials. The use of several noncontrast computed tomography (NCCT) markers has been suggested to stratify the risk of HG. The aim of this study was to analyze HG prediction using different NCCT markers in patients with spontaneous ICH. Methods : Single-hospital retrospective study of patients with spontaneous ICH, who underwent initial NCCT <24 hours after symptom onset. Clinical characteristics were collected and two independent observers analyzed hemorrhage characteristics, volumes and 8 NCCT markers. HG was defined as a growth of ≥33% or ≥6mL in follow-up CT and 30-day survival was collected. Results : 328 patients were included. The most frequent NCCT marker was 'any hypodensity' (68.0%) and the less frequent was the blend sign (11.6%). HG occurred in 22.1% of patients and the only independent predictors for HG were 'any hypodensity' (OR=3.32, 95%CI=1.18-9.34, p=0.023) and the swirl sign (OR=3.98, 95%CI=1.41-11.21, p=0.009). Although all NCCT markers were more frequent in patients who died within 30 days, the only independent predictors were 'irregular margins' (OR=4.54, 95%CI=1.63-12.66, p=0.004) and the satellite sign (OR=2.49, 95%CI=1.07-5.75, p=0.034). NCCT markers with greater sensitivity for HG were 'any hypodensity' and the swirl sign, although with poor positive predictive values and poor areas under the curve. Conclusion : Even though some NCCT markers are independent predictors of HG and 30-day survival, they have suboptimal diagnostic test performances for such outcomes. Abbreviation : OR: odds ratio; 95%CI: 95% confidence interval.

Mikania laevigata, popularly known in Brazil as guaco, is widely used for respiratory disorders. As this plant is rich in coumarins, there is evidence of indications that it may cause bleeding and therefore should not be used concomitantly with anticoagulants. The basis of this information is very theoretical, with no clinical evidence of such contraindication. Thus, the aim of this study was to evaluate the in vitro effect of M. laevigata extract on blood coagulation through prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests, fibrinogen plasma concentration, and the new thrombin generation test, which investigate, with high sensibility, hemostatic changes (CAAE 60904316.6.0000.5149), besides evaluating its qualitative micromolecular composition, providing scientific evidence to support the management of patients taking warfarin. Ethanolic extracts of guaco leaves were incubated with a plasma pool of healthy individuals at concentrations of 1.67, 2.26, and 2.86 mg/mL. The presence of flavonoids, tannins, coumarins, and triterpenes was demonstrated by selective reagents in thin layer chromatography. Benzoylgrandifloric acid, cinnamoylgrandifloric acid, o-coumaric acid, coumarin, and quercetin-3-β-glucoside were identified by coinjection in ultraperformance liquid chromatography. The extract at all concentrations prolonged TP and aPPT and reduced the potential for endogenous thrombin potential by the thrombin generation test. The control plasma had endogenous thrombin potential = 1465 nM/min, and after the addition of M. laevigata extract (2.26 mg/mL), this value was reduced to 1087 nM/min, indicating a lower generation of thrombin. Related to fibrinogen plasma concentration, concentrations of 2.26 and 2.86 mg/mL were effective in reducing plasma fibrinogen levels. These results allow us to conclude that the guaco extract demonstrated an anticoagulant effect in vitro, possibly interfering with intrinsic, extrinsic, and common coagulation pathways. A discussion on the contribution of the identified substances to the activity is also present.

Non-traumatic intracerebral hemorrhage (ICH) is associated with a significant global burden of disease, and despite being proportionally less frequent than ischemic stroke, in 2010 it was associated with greater worldwide disability-adjusted life years lost. The focus of outcome assessment after ICH has been mortality in most studies, because of the high early case fatality which reaches 40% in some population-based studies. The most robust and consistent predictors of early mortality include age, severity of neurological impairment, hemorrhage volume and antithrombotic therapy at the time of the event. Long-term outcome assessment is multifaceted and includes not only mortality and functional outcome, but also patient self-assessment of the health-related quality of life, occurrence of cognitive impairment, psychiatric disorders, epileptic seizures, recurrent ICH and subsequent thromboembolic events. Several scores which predict mortality and functional outcome after ICH have been validated and are useful in the daily clinical practice, however they must be used in combination with the clinical judgment for individualized patients. Management of patients with ICH both in the acute and chronic phases, requires health care professionals to have a comprehensive and updated perspective on outcome, which informs decisions that are needed to be taken together with the patient and next of kin., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction Pathophysiology of cervical artery dissection is complex and poorly understood. In addition to well-known causative and predisposing factors, including major trauma and monogenic connective tissue disorders, morphological characteristics of the styloid process have been recently recognized as a possible risk factor for cervical internal carotid artery dissection. Aims To study the association of the anatomical characteristics of styloid process with internal carotid artery dissection. Methods Retrospective, multicenter, case-control study of patients with internal carotid artery dissection and age- and sex-matched controls. Consecutive patients with internal carotid artery dissection and controls with ischemic stroke or transient ischemic attack of any etiology excluding internal carotid artery dissection, who had performed computed tomography angiography, diagnosed between January 2010 and September 2016. Two independent observers measured styloid process length and styloid process distance to internal carotid artery. Results Sixty-two patients with internal carotid artery dissection and 70 controls were included. Interobserver agreement was good for styloid process length and styloid process-internal carotid artery distance (interclass correlation coefficient = 0.89 and 0.76, respectively). Styloid process ipsilateral to dissection was longer than left and right styloid process in controls (35.8 ± 14.4 mm versus 30.4 ± 8.9 mm and 30.3 ± 8.2 mm, p = 0.011 and p = 0.008, respectively). Styloid process-internal carotid artery distance ipsilateral to dissection was shorter than left and right distance in controls (6.3 ± 1.9 mm versus 7.2 ± 2.1 mm and 7.0 ± 2.3 mm, p = 0.003 and p = 0.026, respectively). Internal carotid artery dissection was associated with styloid process length (odds ratio = 1.04 mm -1 , 95% confidence interval = 1.01-1.08, p = 0.015) and styloid process-internal carotid artery distance (OR = 0.77 mm -1 , 95% confidence interval = 0.64-0.92, p = 0.004). Conclusion Longer styloid process and shorter distance between styloid process and cervical internal carotid artery are associated with cervical internal carotid artery dissection.

Background Double lumen balloon catheters (DLBCs) are currently used in the treatment of intracranial aneurysms, especially when involving balloon or stent-assisted coiling. The existing DLBCs allow the delivery of self-expandable stents but do not offer the possibility to deploy flow-diverters. Despite the increasing use and success of flow-diverters, there have been numerous reports of procedural complications such as early in-stent thrombosis or delayed distal embolization. It seems that these complications can be avoided by correct stent positioning and adequate wall apposition, achieved either by manoeuvres with the microguidewire and/or microcatheter or by performing balloon angioplasty following an exchange guidewire manoeuvre. Objective Report the use of a new DLBC able to deliver a flow-diverter. Methods A 41-year-old woman presented to our hospital with binocular horizontal diplopia for two weeks and reduced visual acuity. A left internal carotid artery aneurysm involving the cavernous and ophthalmic segments was found, with a maximum height of 19 mm and a broad 8 mm neck. It presented extra- and intra-dural components and the parent vessel was significantly narrowed. A decision was made to perform endovascular treatment of the aneurysm with placement of a flow diverter through a DLBC. Results Patency and adequate expansion of the flow diverter with evident intra-aneurysmal contrast stasis was observed in the final angiogram. No peri-procedural complications were observed. Conclusion This is a technical note demonstrating the feasibility of a new device to deploy a flow diverter, aiming to improve wall apposition and stent configuration without the need of additional devices or exchange manoeuvres.

Predictors of short-term readmission after ischemic stroke have been previously identified, but few studies analyzed predictors of long-term readmission, namely early imaging findings and treatment with intravenous thrombolysis (IVT). To characterize predictors of hospital readmission during the first year after hospitalization for ischemic stroke. The study consists of a retrospective cohort of consecutive ischemic stroke patients admitted in a Portuguese university hospital during 2013, who survived index hospitalization. We collected clinical and imaging information using the electronical clinical record. Information concerning 1-year unplanned hospital readmissions was assessed using the Portuguese electronic Health Data Platform. Descriptive and univariate analyses, Kaplan-Meier survival curve and multivariate survival analysis with Cox regression model were used. We included 480 patients, 50.6 % women, median age 79 years (interquartile range = 68-85). One-year hospital readmissions occurred in 165 patients [34.4 %, 95 % confidence interval (95 % CI) 30.2-38.7]. The main causes for readmission were infectious diseases (43.8 %), ischemic stroke or transient ischemic attack recurrence (13.2 %) and cardiac diseases (6.4 %). In-hospital mortality associated with readmission was 23.0 %. The independent predictors of 1-year hospital readmission after ischemic stroke were admission mini-National Institute of Health Stoke Scale [hazards ratio (HR) 1.05, 95 % CI 1.02-1.08, p = 0.002], and mild or absent early signs of ischemia on admission computed tomography (CT) (HR 0.54, 95 % CI 0.32-0.91, p = 0.021) and IVT (HR 0.11, 95 % CI 0.01-0.80, p = 0.029). Hospital readmission during the first year after ischemic stroke occurs in 1/3 of patients and is associated with high in-hospital mortality. Clinical stroke severity, early signs of ischemia on admission CT, and treatment with IVT are independent predictors of 1-year hospital readmission.

Objective: Orolingual angioedema (OA) is a well known early complication of treatment with alteplase in ischemic stroke patients. Our aim was to study risk factors for OA in these patients, namely insular cortex ischemia., Methods: Retrospective case-cohort study using the prospective registry of all consecutive ischemic stroke patients submitted to intravenous thrombolysis with alteplase. Clinical data was retrieved from the registry and medical records. Two independent observers evaluated early signs of insular cortex ischemia on pre-thrombolysis computed tomography (CT) and of insular cortex infarct on early follow-up imaging. Univariate and multivariate analysis were performed to identify predictors of OA., Results: Of the 659 patients with acute ischemic stroke treated with alteplase, 32 developed OA (4.9%, 95%CI=3.3-6.6). Frequency of early signs of insular cortex ischemia on pre-thrombolysis CT and of insular cortex infarct on follow-up imaging was similar in patients with and without OA (p=0.241 and p=0.145, respectively). The only independent predictors of OA occurrence were female sex (OR=5.47, 95%CI=1.98-15.10) and angiotensin-converting enzyme inhibitor (ACE-I) use (OR=3.87, 95%CI=1.71-8.75)., Conclusions: Female sex and ACE-I use are independent risk factors for OA occurrence in ischemic stroke patients treated with alteplase. Early signs of insular cortex ischemia on pre-thrombolysis CT were not significantly associated with OA., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: Cerebral gas embolism (CGE) is a potentially catastrophic complication of central venous catheters (CVCs) manipulation or accidental disconnection, which is rarely reported in the literature. This systematic review aims to characterize the clinical manifestations, imaging features and outcome of CGE associated with CVCs., Methods: Systematic literature search of all published cases of CGE associated with CVCs, and identification of previously unreported local cases. Descriptive analysis of all cases, mortality analysis for cases with individualized data., Results: Of the 158 patients with CGE associated with CVCs found, 71.8% were male and mean age was 56.4years. CGE symptoms frequently occurred while in the upright position. The most frequent neurological manifestation was sudden-onset focal neurological sign (67.7%), followed by coma (59.5%), epileptic seizures (24.7%) and encephalopathy (21.5%). Imaging revealed intracranial air bubbles in 69.1% and cerebral ischemia or edema was demonstrated in 66.7%. Overall mortality was 21.7%, and clinical predictors of mortality were increasing age (p<0.001), coma (p=0.001), cardiorespiratory arrest shortly after symptom onset (p<0.001) and male sex (p=0.035)., Conclusions: CGE associated with CVCs may mimic ischemic stroke, but patients frequently present a severe vigilance disturbance and epileptic seizures. Mortality occurs in 1/5 of patients, which substantiates implementation of protocols and measures to prevent this severe complication of CVC use., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Wake-up stroke (WUS) represents 25% of all ischemic strokes. There is conflicting evidence concerning clinical severity, imaging characteristics, and outcome when WUS is compared with stroke of known time of onset. Our aim was to compare WUS patients with patients with ischemic stroke within the therapeutic window (STW) for thrombolysis., Methods: This is a retrospective hospital-based study of all consecutive patients hospitalized for acute ischemic stroke during 2013. Patients with STW, WUS, and WUS with computed tomography (CT)  at 3 hours or less after awakening (WUS≤3h) were selected for the study. The methods used include a review of clinical records, an independent quantification of early signs of ischemia on admission CT scan, and determination of functional outcome on follow-up., Results: Of 554 patients evaluated, 190 had STW, 113 had WUS (20.4%), and 25 had WUS≤3h. Among all WUS patients, 33.6% did not have any other formal contraindication for thrombolysis besides undetermined time of onset. WUS patients had demographic characteristics, vascular risk factors, and clinical severity similar to STW patients. Mild or absent early signs of ischemia on admission CT in WUS≤3h patients were similar to those in STW patients when adjusted for clinical severity (odds ratio [OR] = .50, 95% confidence interval [CI]=.17-1.47). Favorable prognosis in WUS≤3h was similar to STW when adjusted for age, clinical severity, and thrombolysis (OR = .53, 95% CI=.09-3.14)., Conclusions: This study strengthens the evidence that clinical and early imaging characteristics of WUS patients are similar to those of patients with stroke who are eligible for thrombolysis based on the time window criteria, and patients with WUS do not have a worse short outcome., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Paroxysmal dystonia is a rare manifestation of multiple sclerosis (MS)., Case Report: A 41-year-old man presented to our Emergency Department with sudden and repeated episodes of left upper limb flexion and lower limb extension. His medical history included an episode of left facial palsy a year earlier. Neurological examination demonstrated only brisk deep tendon reflexes on the left upper limb. Routine blood and urine analyses were normal. Computed tomography of the brain and cervical Doppler were normal. Aspirin and sodium valproate were started, without improvement. Video-EEG monitoring revealed no electrographic abnormality synchronous with these paroxysmal events, excluding epileptic nature. Cerebral magnetic resonance imaging showed multiple T2 white matter lesions at the midbrain, right diencephalon, corpus callosum, cervical, and thoracic spinal cord. The right diencephalic lesion enhanced with gadolinium. Complete basic and immunologic analysis and serological studies were normal or negative. Oligoclonal bands were positive in cerebrospinal fluid (negative in serum). Methylprednisolone (1 g/d for 5 d) was started without clinical improvement. Carbamazepine (400 mg/d) was promptly effective, and discontinued after 1 month without recurrence., Discussion: The patient met the criteria for the diagnosis of MS according to the 2010 McDonald criteria. The timely and accurate diagnosis of MS requires the recognition of its varied and atypical clinical manifestations.

The tick Rhipicephalus microplus causes significant losses in livestock cattle and has developed increasing resistance to the primary acaricides that are used to treat these infections. The objective of this study was to identify new biomolecules or isolated substances showing acaricidal activity from plants. Larval packet tests were conducted to evaluate the effects of 11 species of plants and three isolated substances (betulinic acid, eugenol, and nerolidol) on R. microplus. An adult female immersion test was performed with the substance that showed the highest larvicidal activity, which was evaluated for inhibition of reproduction. Tests using Licania tomentosa, Hymenaea stigonocarpa, Hymenaea courbaril, Stryphnodendron obovatum, Jacaranda cuspidifolia, Jacaranda ulei, Struthanthus polyrhizus, Chrysobalanus icaco, Vernonia phosphorea, Duguetia furfuracea, and Simarouba versicolor extracts as well as the isolated substance betulinic acid indicated lower acaricidal effects on R. microplus larvae. The extract displaying the best larvicidal activity was the ethanolic extract from L. tomentosa at a concentration of 60%, resulting in a mortality rate of 40.3%. However, nerolidol and eugenol showed larvicidal activity, which was highest for eugenol. Nerolidol caused a 96.5% mortality rate in the R. microplus larvae at a high concentration of 30%, and eugenol caused 100% mortality at a concentration of 0.3%. In the adult immersion test, 5% eugenol was identified as a good biomolecule for controlling R. microplus, as demonstrated by its high acaricidal activity and inhibition of oviposition.

This two-year study investigated the epidemiology of nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) among patients and healthcare workers (HCWs) in two wards with a high frequency of MRSA isolation, at Hospital Geral de Santo António (HGSA), Portugal. Three point-prevalence surveys per year were carried out. A case-control approach was used to identify potential risk factors associated with MRSA carriage among patients. Incidence rates and risk factors of MRSA carriage among HCWs who were negative at the baseline observation were estimated. Prevalence of MRSA carriage among 276 patients screened was 5.1%. Admission to HGSA or attendance to the Diabetic Foot Outpatient Unit (DFOU) of HGSA within the past 12 months, and previous MRSA isolation were significant risk factors for MRSA carriage. Among HCWs (n = 126), the prevalence of MRSA carriage was 4.8% and the incidence rate was 61/1000 person-years. Nurses and nurse aids were the HCW categories with the highest risk of becoming colonized with MRSA over time (p = 0.01). One HCW chronically colonized was detected. Molecular typing revealed a clonal identity for isolates recovered from patients and HCWs of the same wards, with 88.6% of isolates belonging to the EMRSA-15 (ST22-MRSA-IV) clone.

Objective: To study the acquisition and cross-transmission of Staphylococcus aureus in different intensive care units (ICUs)., Methods: We performed a multicenter cohort study. Six ICUs in 6 countries participated. During a 3-month period at each ICU, all patients had nasal and perineal swab specimens obtained at ICU admission and during their stay. All S. aureus isolates that were collected were genotyped by spa typing and multilocus variable-number tandem-repeat analysis typing for cross-transmission analysis. A total of 629 patients were admitted to ICUs, and 224 of these patients were found to be colonized with S. aureus at least once during ICU stay (22% were found to be colonized with methicillin-resistant S. aureus [MRSA]). A total of 316 patients who had test results negative for S. aureus at ICU admission and had at least 1 follow-up swab sample obtained for culture were eligible for acquisition analysis., Results: A total of 45 patients acquired S. aureus during ICU stay (31 acquired methicillin-susceptible S. aureus [MSSA], and 14 acquired MRSA). Several factors that were believed to affect the rate of acquisition of S. aureus were analyzed in univariate and multivariate analyses, including the amount of hand disinfectant used, colonization pressure, number of beds per nurse, antibiotic use, length of stay, and ICU setting (private room versus open ICU treatment). Greater colonization pressure and a greater number of beds per nurse correlated with a higher rate of acquisition for both MSSA and MRSA. The type of ICU setting was related to MRSA acquisition only, and the amount of hand disinfectant used was related to MSSA acquisition only. In 18 (40%) of the cases of S. aureus acquisition, cross-transmission from another patient was possible., Conclusions: Colonization pressure, the number of beds per nurse, and the treatment of all patients in private rooms correlated with the number of S. aureus acquisitions on an ICU. The amount of hand disinfectant used was correlated with the number of cases of MSSA acquisition but not with the number of cases of MRSA acquisition. The number of cases of patient-to-patient cross-transmission was comparable for MSSA and MRSA.

Two hundred eighty methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates recovered from a tertiary care hospital in Oporto, Portugal, between 2003 and 2005 were studied by a combination of molecular typing techniques in order to investigate the genetic backgrounds associated with the changes in the resistance phenotypes observed since 2001 and compare them to those previously found in the hospital. All MRSA isolates were grouped into resistance profiles for a panel of seven antibiotics and characterized by pulsed-field gel electrophoresis (PFGE) and SCCmec (staphylococcal cassette chromosome mec) typing. Representative isolates of PFGE types were further studied by spa typing and multilocus sequence typing. Our findings clearly document that the increasing isolation of nonmultiresistant MRSA strains was associated with the decline (from 69% in 1996 to 2000 to 12% in 2003 to 2005) and massive replacement of the multiresistant Brazilian clone (ST239-IIIA) by the epidemic EMRSA-15 clone (ST22-IV), in which resistance to antibiotics other than beta-lactams is very rare, as the major clone (80% of isolates). The Iberian clone (ST247-IA), a major clone in 1992 to 1993, was represented in the present study by just one isolate. Two other pandemic MRSA clones were detected, as sporadic isolates, for the first time in our hospital: the New York/Japan (ST5-II) and the EMRSA-16 (ST36-II) clones. Furthermore, the pattern of susceptibility of MRSA isolates both to gentamicin and to trimethoprim-sulfamethoxazole was shown to be an excellent phenotypic marker for the discrimination of the EMRSA-15 clone from other nonmultiresistant MRSA clones present in our hospital.

We evaluated three rapid methods to detect methicillin-resistant Staphylococcus aureus (MRSA) and compared them with PCR amplification of mecA. A total of 103 S. aureus strains were studied by MRSA-Screen, BBL Crystal, Velogene Genomic and mecA PCR. All the methods detected the 61 MRSA strains having the mecA gene, showing 100% sensitivity and specificity. Despite the correlation between all the rapid methods and PCR, the ease of use and shorter turnaround time of MRSA-Screen were important factors leading to the selection of this method as the routine screening technique for MRSA.

We evaluated the incidence of dermatophytes isolated at our hospital in the years of 1997 to 2000 and correlated it with anatomical site and age. Trichophyton rubrum was the predominant species in all anatomical sites, excluding scalp, followed by Microsporum canis, the leading agent of tinea capitis. All dermatophytosis, except tinea capitis by M. canis and Trichophyton schoenleinnii appeared mainly in adult patients. Our results revealed no substantial differences to other portuguese studies regarding the major agents. We found a relatively high incidence of T. schoenleinnii as second tinea capitis agent.

Methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered from a general hospital in Oporto, Portugal, during two periods (1992-1993 and 1996-2000) were characterized by pulsed-field gel electrophoresis (PFGE) of SmaI fragments, and by hybridization of ClaI digests with mecA and Tn554 probes, discriminating the isolates in mecA::Tn554::PFGE genotypes. In addition, a representative sample of the defined genotypes was characterized by multilocus sequence typing (MLST) and SCCmec (staphylococcal cassette chromosome mec) typing, generating the corresponding ST-SCCmec types. In 1992-1993, 77% of MRSA belonged to the Iberian clone (genotype I::E::A or ST247-IA). In 1996-2000, the frequency of this clone decreased to 19% and the majority (69%) of the isolates belonged to another international clone, the Brazilian MRSA (genotype XI::B::B or ST239-IIIA). Trimethoprim/sulfamethoxazole (SXT) was confirmed to be an important phenotypic marker to distinguish the Iberian (SXT-susceptible) and the Brazilian (SXT-resistant) clones in MRSA isolates from Portugal. Our observations document major shifts in the dominant MRSA clonal types that occurred in this hospital since 1992, suggesting a selective advantage of the Brazilian relatively to the Iberian clone. In addition to these two MRSA clones that are the most frequent in Portuguese hospitals since the early 1990s, sporadic MRSA clones (representing 14% of the total) were identified and characterized.

Background: PCR detection of CSF Herpes virus DNA is an important tool in the diagnosis of CNS infections. Use of this test has been shown to have an impact on patient management as measured by shortened patient stays, specific therapeutic intervention, reduction of empirical expensive therapy administration, all of which should translate into significant health care savings., Objective: The present study aimed at implementing, and evaluating both clinically and analytically the performance of several commercially available PCR based assays for the detection of Herpes virus infections of the CNS., Study Design: A total of 314 patients with suspected CNS Herpesvirus infection were investigated, between 1999 and 2001, by Stair primers PCR. Starting on January 2002, two commercially available real-time-PCR systems were implemented and tested using the Stair primers PCR assay as golden standard and three external control proficiency panels along with serial dilutions of positive clinical samples., Results: Sensitivity of the assay was determined to be <200 copies per ml for HSV and <1250 copies per ml for CMV. Positive results were obtained for 17 patients (6 HSV-1, 1 HSV-2, 1 EBV, 1 CMV, 6 VZV and 2 HHV-6) whose clinical and analytical findings were consistent with the PCR results. A real-time-PCR procedure was introduced in 2002 with similar sensitivity, but a more rapid response., Conclusion: Conventional end-point PCR proved useful to the diagnosis of CNS herpes virus infection, with an impact on the clinical intervention. However, the use of Real-Time-PCR has greatly enhanced these advantages, making results available at a much earlier time, thus significantly reducing the need for empirical treatment.

Background: CMV is a major clinical problem in transplant recipients. Thus, it is important to use sensitive and specific diagnostic techniques to rapidly and accurately detect CMV infection and identify patients at risk of developing CMV disease. In the present study, CMV infection after liver transplantation was monitored retrospectively by two molecular biology assays - a quantitative PCR assay and a qualitative NASBA assay. The results were compared with those obtained by prospective pp65 antigenemia determinations., Materials and Methods: 87 consecutive samples from 10 liver transplanted patients were tested for CMV by pp65 antigenemia, and CMV monitor and NASBA pp67 mRNA assay., Results: CMV infection was detected in all patients by antigenemia and CMV monitor, whereas NASBA assay identified only 8/10 patients with viremia. Furthermore, CMV infection was never detected earlier by molecular biology assays than by antigenemia. Only 5/10 patients with CMV infection developed CMV disease. Using a cut off value of 8 cells/50,000, antigenemia was found to be the assay that better identified patients at risk of developing CMV disease. However, the kinetics of the onset of infection detected by NASBA and CMV monitor seemed to have better identified patients at risk of developing CMV disease. Furthermore, before onset of disease, CMV pp67 mRNA was found to have similar or better negative and positive predictive values for the development of CMV disease., Conclusions: The present data, suggests that the concomitant use of antigenemia and pp67 mRNA assay gives the best identification of patients at risk of developing CMV disease.