Absence Of Hemorrhage Research Articles

Anti-inflammatory and antioxidant activity of hydroethanolic extract of Spondias mombin leaf in an oral mucositis experimental model

BackgroundSpondias mombin has been used in folk medicine to treat inflammation in the oral cavity. This study aimed to evaluate the antioxidant and anti-inflammatory activity of S. mombin extract in an oral mucositis experimental model. MethodsMale hamsters were orally pre-treated with hydroethanolic extract of S. mombin leaves (HESM) (50, 100, or 200 mg/kg) for ten days. Cheek pouch samples were subjected to macroscopic, histopathological and immunohistochemical analysis (Cox-2, iNOS, NF-kB p50 NLS and MMP-2). IL-1β and TNF-α levels were analyzed by ELISA immunoassay, and Superoxide dismutase estimative (SOD), glutathione (GSH) and malondialdehyde (MDA) levels were submitted to spectroscopy analysis. ResultsThe group treated with HESM at a dose of 200 mg/kg showed the best healing effect, showing no evidence of ulceration in the macroscopic analysis (p < 0.05). Histopathological analysis showed re-epithelialization, discrete mononuclear inflammatory infiltrate and absence of hemorrhage and edema score of 1 (1-1) (p < 0.05), as well as a large amount of collagen fibers and a lower immunoexpression of Cox-2, iNOS, NF-kB p50 NLS and MMP-2. Decrease in SOD (p < 0.05), MDA (p<0.001), IL-1β (p < 0.05), and TNF-α levels (p < 0.001), with an increase in GSH (p < 0.01) levels. ConclusionHESM (200 mg/kg) reduced oxidative stress and inflammation in the 5-fluorouracil-induced oral mucositis in hamsters.

DCE-MRI perfusion predicts pseudoprogression in metastatic melanoma treated with immunotherapy.

It can be challenging to differentiate pseudoprogression from progression. We assessed the ability of dynamic contrast enhanced T1 MRI (DCE-MRI) perfusion to identify pseudoprogression in melanoma brain metastases. Patients with melanoma brain metastases who underwent immunotherapy and DCE-MRI were identified. Enhancing lesions ≥ 5mm in diameter on DCE-MRI and that were new or increased in size between a week from beginning the treatment, and a month after completing the treatment were included in the analysis. The 90th percentiles of rVp and rKtrans and the presence or absence of hemorrhage were recorded. Histopathology served as the reference standard for pseudoprogression. If not available, pseudoprogression was defined as neurological and radiographic stability or improvement without any new treatment for ≥ 2months. Forty-four patients were identified; 64% received ipilimumab monotherapy for a median duration of 9weeks (range, 1-138). Sixty-four lesions in 44 patients were included in the study. Of these, nine lesions in eight patients were determined to be pseudoprogression and seven lesions were previously irradiated. Forty-four progression lesions and eight pseudoprogression lesions were hemorrhagic. Median lesion volume for pseudoprogression and progression were not significantly different, at 2.3 cm3 and 3.2 cm3, respectively (p = 0.82). The rVp90 was smaller in pseudoprogression versus progression, at 2.2 and 5.3, respectively (p = 0.02), and remained significant after false discovery rate adjustment (p = 0.04). Pseudoprogression exhibited significantly lower rVp90 on DCE-MRI compared with progression. This knowledge can be useful for managing growing lesions in patients with melanoma brain metastases who are receiving immunotherapy.

Interventions for treating brain arteriovenous malformations in adults.

Brain arteriovenous malformations (AVMs) are the single most common cause of intracerebral haemorrhage in young adults. Brain AVMs also cause seizure(s) and focal neurological deficits (in the absence of haemorrhage, migraine or an epileptic seizure); approximately one-fifth are incidental discoveries. Various interventions are used in an attempt to eradicate brain AVMs: neurosurgical excision, stereotactic radiosurgery, endovascular embolization, and staged combinations of these interventions. This is an update of a Cochrane Review first published in 2006, and last updated in 2009. To determine the effectiveness and safety of the different interventions, alone or in combination, for treating brain AVMs in adults compared against either each other, or conservative management, in randomized controlled trials (RCTs). The Cochrane Stroke Group Information Specialist searched the Cochrane Stroke Group Trials Register (last searched 7 January 2019), the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 1) in the Cochrane Library, MEDLINE Ovid (1980 to 14 January 2019), and Embase OVID (1980 to 14 January 2019). We searched international registers of clinical trials, the contents pages of relevant journals, and bibliographies of relevant articles (November 2009). We also contacted manufacturers of interventional treatments for brain AVMs (March 2005). We sought RCTs of any intervention for brain AVMs (used alone or in combination), compared against each other or against conservative management, with relevant clinical outcome measures. One author screened the results of the updated searches for potentially eligible RCTs for this updated review. Both authors independently read the potentially eligible RCTs in full and confirmed their inclusion according to the inclusion criteria. We resolved disagreement by discussion. We assessed the risk of bias in included studies and applied GRADE. We included one trial with 226 participants: A Randomized trial of Unruptured Brain Arteriovenous Malformations (ARUBA), comparing intervention versus conservative management for unruptured brain AVMs (that had never bled). The quality of evidence was moderate because we found just one trial that was at low risk of bias other than a high risk of performance bias due to participants and treating physicians not being blinded to allocated treatment. Data on functional outcome and death at a follow-up of 12 months were provided for 218 (96%) of the participants in ARUBA. In this randomized controlled trial (RCT), intervention compared to conservative management increased death or dependency (modified Rankin Scale score ≥ 2, risk ratio (RR) 2.53, 95% confidence interval (CI) 1.28 to 4.98; 1 trial, 226 participants; moderate-quality evidence) and the proportion of participants with symptomatic intracranial haemorrhage (RR 6.75, 95% CI 2.07 to 21.96; 1 trial, 226 participants; moderate-quality evidence), but there was no difference in the frequency of epileptic seizures (RR 1.14, 95% CI 0.63 to 2.06; 1 trial, 226 participants; moderate-quality evidence). Three RCTs are ongoing. We found moderate-quality evidence from one RCT including adults with unruptured brain AVMs that conservative management was superior to intervention with respect to functional outcome and symptomatic intracranial haemorrhage over one year after randomization. More RCTs will help to confirm or refute these findings.

Nonconformities in Veterinary Cytopathological Examinations: A Retrospective Study of Unsuitable Samples for Analysis

Abstract The aim of this study was to evaluate the main nonconformities that result in cytopathological samples inappropriate for diagnosis in veterinary medicine. All cytopathological samples, obtained from different canine and feline tissues/lesions, included in the study were received and classified as inconclusive by a single public laboratory of veterinary pathology, located in Pernambuco State, Brazil, between 2012 and 2016. Nonconformities regarding the smear quality, cellularity, presence or absence of hemorrhage, cellular overlapping, desiccation, and presence or absence of necrotic debris and/or artifacts were evaluated. Data were tabulated using Microsoft Excel 2007; absolute and relative frequencies were calculated using EPIINFO 3.5.2. From the 3268 cases received between 2012 and 2016, 190 cases were selected and comprised 514 inconclusive slides. The most frequent nonconformities detected were insufficient/absence of cellularity in 100% (514/514), inadequate submacroscopic presentation in 87% (446/514), and hemorrhage in 69% (356/514) of samples. Other features identified were cellular overlapping in 34% (175/514), inadequate staining in 31% (175/514), artifacts in 30% (154/514), desiccation in 28% (145/514), and necrotic debris in 26% (133/514) of samples. The implementation of laboratory standard operational procedures aimed at maintaining quality is essential. It is necessary to initially identify the main errors occurring in the processing stages as a way to guide and design strategies to avoid them.

CT Findings of Acute Stroke– Study of 321 Cases

Stroke ranks first in frequency among all the neurological diseases of adult life and about 50% of all neurological disorders in a hospital are of this type. It is the third leading cause of death throughout the world. The purpose of the present study was to find out the presence or absence of haemorrhage or infarct and to detect the early signs of stroke on the basis of CT scanning. Three-hundred twenty one consecutive acute stroke patients (mean age 64 ±9.75 years) were included in our study. Each underwent cranial computed tomography without intravenous contrast injection within the first 24 hours. CT findings of stroke were analyzed using SPSS software. Among 321 patients, 209(65.11%) had ischemic stroke, 99(30.84%) had parenchymal haemorrhage and 13(4.05%) had subarachnoid haemorrhage. Total amount of haemorrhagic stroke was 112(34.89%). Early CT findings of ischaemic stroke were low attenuation area (83.25%), sulcal effacement (69.89%), loss of the insular ribbon (17.70%), hyperdense artery sign (1.43%). CT scanning should be the first line of investigation for diagnosis of acute stroke as it is more available than MRI and is easily performed in severely ill patients who are dependent on support and monitoring devices&#x0D; TAJ 2019; 32(1): 17-24

Factors associated with extended remission in neovascular age-related macular degeneration on pro re nata treatment protocol

AimTo show the characteristics and outcomes of patients with neovascular age-related macular degeneration (nAMD) who had extended remission (ER) while on a pro re nata (PRN) treatment protocol.MethodsThis was a...

SUN-426 A Case of Pseudo-Apoplexy: An Unexplored Mechanism of Acute Pituitary Failure

A 70-year old male came in with a 2-week history of drowsiness, generalized body weakness, anorexia, occasional nausea and vomiting that started with a sudden onset of headache during his flight from Michigan, USA to the Philippines without any history of trauma. His headache resolved upon arrival in Manila, however, weakness persisted and he had repeated hyponatremia on hospital consults with essentially normal physical and neurologic findings. Hormonal work-up was done and revealed panhyopituitarism. All symptoms resolved within 2 days of initiating hydrocortisone at physiologic dose. Cranial MRI confirmed presence of a pituitary mass (1.7 x 1.7 x 1.5 cm) with pituitary apoplexy for which the patient underwent endoscopic transsphenoidal transpterygoid surgery. However, histopathology report showed a rathke’s cleft cyst without findings of hemorrhage or infection. Evidences of the dynamic nature of rathke’s cleft cysts have all been clinical, circumstantial and scarce due to the difficulty in diagnosis and documentation. However, cases of acute hypopituitarism in the absence of hemorrhage, infarct, infection or trauma, suggests another pathophysiology of disease that has not yet been extensively reported. This case supports a mechanism of either cyst expansion with encroachment on neighboring structures and/or cerebral edema potentially triggered by changes in atmospheric pressure with international commercial flights flying at approximately 30,000 ft. At higher altitudes, lower partial pressure of oxygen causes relative cerebral hypoxia. Consequently, vascular permeability increases due to the upregulation of vascular endothelial growth factors promoting cerebral edema. This has previously been reported with manifestations more commonly known as acute mountain sickness (AMS) and high altitude cerebral edema (HACE) when associated with life-threatening neurologic deterioration. For patients already with intracranial space occupying lesions, development of minimal edema becomes significant. A slight Increase in mass size or volume of cerebrospinal fluid in smaller spaces such as the sella, are more likely to display symptoms. Therefore, caution should be advised for patients with known intracranial masses who are not to undergo surgery and are planning to travel or stay at high altitudes. Furthermore, rathke’s cleft cysts should be considered as a differential diagnosis to apoplexy-like presentations, especially in those patients who have relatively benign or non-persistent symptoms easily resolving with hormone replacement.

SUN-LB070 Who Killed the Pituitary?

Background: Pituitary apoplexy can be caused by factors like surgery, pregnancy, drugs including anticoagulants and bromocriptine. Chemotherapy as a causal factor, however, has not often been noted in literature. To our knowledge, there are only 2 case reports implicating chemotherapy drugs as a cause of pituitary apoplexy. 1 Case: 72 year old male with recently discovered squamous cell lung cancer, presented to clinic for assessment of incidental pituitary mass noted on staging imaging. Initial labs showed hypogonadotropic hypogonadism with normal PRL, TSH and HPA axis. Transphenoidal biopsy of mass showed no metastasis. Subsequently, he was started on carboplatin and paclitaxel for lung cancer. Initial course was complicated by deep venous thrombosis treated with enoxaparin. After his sixth chemotherapy cycle, he presented with sudden onset headache and diplopia consistent with sixth cranial nerve palsy. Initial CT head was negative for hemorrhage and stable, though hypoenhancing sellar mass. Sixth nerve palsy was initially thought to be due to microvascular ischemic event. Labs at this time were notable for undetectable PRL, low TSH (0.03 uIU/ml, N 0.35-4.9 uIU/ml), declining ACTH (14 to 9 pg/ml, N 6-50 pg/ml). He developed significant hyponatremia, concerning for central adrenal insufficiency, requiring urgent treatment with stress dose steroids. Pituitary MRI newly showed enlarging sellar mass, defect in dura and retroclival collection, later thought to be necrotic material from apoplectic pituitary. Surgical intervention was deferred as ophthalmology exam showed no pituitary compromise. After 12 days, he was readmitted with atraumatic bilateral subdural hematomas (SDHs) prompting enoxaparin cessation. Imaging at this time also showed decreased size of the mass. Follow up imaging showed resolution of SDHs with interval reduction of mass size. On final review, his presentation was suspected to be secondary to pituitary apoplexy due to chemotherapy in conjunction with enoxaparin, causing retroclival necrotic tissue and meningeal irritation leading to atraumatic SDHs. Given absence of hemorrhage on initial imaging and known vasculopathic effects of agents like carboplatin (analog of cisplatin), chemotherapy induced apoplexy cannot be excluded. In addition, although rapid regression after pituitary apoplexy has been reported rarely, chemotherapy may have a role in rapid shrinkage post apoplexy. 2 Conclusion: This case highlights potential role of chemotherapy in conjunction with anticoagulation in causing pituitary apoplexy and rapid pituitary tumor shrinkage. Reference: 1. Jang, Je Hun et al. Extensive Pituitary Apoplexy after Chemotherapy in a Patient with Metastatic Breast Cancer Brain tumor research and treatment vol. 6,1: 43-46 2. Jackson, D. L et al. Rapid pituitary apoplexy regression: what is the time course of clot resolution? Case reports in radiology, 2015 Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Gliclazide Prevents 5-FU-Induced Oral Mucositis by Reducing Oxidative Stress, Inflammation, and P-Selectin Adhesion Molecules.

Oral mucositis (OM) is one of the main side effects of the head and neck cancer treatment, particularly radiotherapy and/or chemotherapy. OM is characterized by ulcers, erythema, dysphagia, xerostomia, and increased susceptibility to opportunistic infections. In the perspective of finding pharmacological therapies to prevent inflammation and ulceration of OM, the investigation of the pleiotropic effect of commercial drugs is needed, among them gliclazide, an antidiabetic drug. This study aimed to evaluate the effect of gliclazide in an experimental OM model induced by 5-fluorouracil. Male hamsters were pre-treated with oral gliclazide (1, 5, or 10 mg/kg) for 10 days. Cheek pouch samples were subjected to histopathological and immunohistochemical analysis (COX2, iNOS, MMP-2, NFκB P65, GPx) and imunofluorescence (P-selectin). IL-1β and TNF-α levels, Myeloperoxidase activity (MPO) and malondialdehyde (MDA) levels were investigated by ultraviolet-visible spectroscopy analysis. NFκB NLS P50 protein levels were analyzed by western blotting. The group treated with gliclazide at a dose of 10 mg/kg showed presence of erythema, no evidence of erosion, and absence of mucosal ulceration with a score of 1 (1–2) (p < 0.01). Histopathological data for the group treated with gliclazide 10 mg/kg showed re-epithelialization, discrete mononuclear inflammatory infiltrate and absence of hemorrhage, edema, ulcers and abscesses with a score of 1 (1–1) (p < 0.01). Treatment with gliclazide 10 mg/kg reduced MPO activity (p < 0.001), MDA levels (p < 0.001) and NFκB NLS P50 (p < 0.05) protein levels, resulting in low immunostaining to Cox-2, iNOS (p < 0.05), NFκB P65 (p < 0.05), and negative immunoreaction to MMP-2 (p < 0.001). However, it appeared that for Gpx1, the staining was restored in the GLI 10-FUT group compared with 5FUT/saline (p < 0.05). Immunofluorescence revealed decreased levels of P-selectin (p < 0.001) after treatment with gliclazide 10 mg/kg (p < 0.05). In summary, gliclazide accelerated mucosal recovery and reduced oxidative stress and inflammation in the 5-FU-induced OM in hamsters.

A Cross-Sectional Observational Study of Nailfold Capillary Morphology in Uveitis

ABSTRACTPurpose: We performed nailfold capillary microscopy to explore microvasculature abnormalities in uveitis overall and uveitis stratified in various ways.Methods: This was a cross-sectional, case–control, observational study. One hundred and seven uveitis patients and 130 control subjects were included. We used a JH-1004 capillaroscope to perform nailfold capillary video microscopy on the fourth and fifth digits of each subject’s nondominant hand. Videos were evaluated for hemorrhages, dilated capillary loops > 25 µm, and avascular zones > 200 µm. Univariate analyses were used for the assessment of case–control morphological differences and multivariate analyses were performed to assess the relation between nailfold capillaroscopic findings and uveitis subgroups.Results: In univariate analysis, uveitis patients were more likely to have higher tortuosity ratings and reduced capillary density compared to controls (p < 0.001 for both); furthermore, dilated capillary loops, avascular zone and hemorrhages were more frequent in uveitis versus control subjects (p < 0.001 for all). Among cases, every unit increase in capillary density (vessels/mm) was associated with active uveitis (n = 72 cases) versus inactive disease (n = 35 cases; odds ratio (OR) = 1.7; (95% confidence interval (CI), 1.2–2.5) in multivariate analysis. Furthermore, the presence of any nailfold hemorrhage versus the absence of hemorrhage was more likely to be associated with posterior and panuveitis (n = 41 cases combined) compared to anterior and intermediate uveitis (n = 66 cases combined; OR = 5.8; 95% CI, 2.3–14.2). Moreover, we found a positive correlation between peripheral retinal leakage and nailfold capillaries dilation (r = 0.33; p = 0.015) that was not strictly significant based on the number of comparisons made.Conclusions: Our study provides support for non-ocular capillary bed abnormalities in uveitis, with interesting correlations based on disease stage and anatomical classification.

Classical metaphyseal lesions thought to be pathognomonic of child abuse are often artifacts or indicative of metabolic bone disease

ObjectiveThe objective of the present study was to review the histopathology in the original articles by authors Kleinman and Marks that described the specificity of the classical metaphyseal lesion for child abuse and to determine if there were any oversights in the authors’ analysis. MethodsWe reviewed the histopathology of the original studies that equated the classical metaphyseal lesion with child abuse. We compared this with the histopathology of metaphyseal fractures caused by known accidental, severe trauma in children and reviewed the histopathology of artifacts that can sometimes be produced in bone histology preparations. ResultsAcute classical metaphyseal lesions showed no hemorrhage, and the chronic classical metaphyseal showed islands of cartilage proliferation at the metaphyses and growth plate, findings consistent with rickets and other metabolic bone disorders. Some of the acute metaphyseal lesions were consistent with artifacts. ConclusionWe believe the original studies that equate the classical metaphyseal lesion with child abuse are flawed. The most compelling observation that challenges the histopathology of the classical metaphyseal lesion as being a fracture is the absence of hemorrhage in the acute classical metaphyseal lesion. We hypothesize that some of the classical metaphyseal lesions were artifacts or represent metabolic bone disorders that were not considered and that these two non-traumatic explanations may have been the basis of the abnormal bone findings.

Multiparametric MR imaging of peripheral zone prostate cancer: effect of postbiopsy hemorrhage on cancer detection according to Gleason score and tumour volume.

To evaluate effect of postbiopsy hemorrhage on detection of peripheral zone (PZ) prostate cancer by multiparametric MR imaging according to Gleason score and tumor volume. This retrospective study included 54 biopsy-proven prostate cancer patients (median age, 67.0 years) who underwent multiparametric MR imaging. Two independent readers evaluated each sextant of the PZ using the PI-RADS v2. One reader recorded the presence or absence of hemorrhage per sextant on T1weighted MR images. Areas under the receiver operating characteristic curves (AUCs) were used to evaluate cancer detection accuracy. Postbiopsy hemorrhage was noted in 122 (37.7%) of 324 sextants of all patients. There was no significant difference in the AUC for detection of cancer with Gleason score≥3+4 or volume≥0.5 ml between sextants with and without hemorrhage (with hemorrhage, reader 1, 0.83 for Gleason score≥3+4, 0.84 for tumor volume≥0.5 ml; reader 2, 0.74 for Gleason score≥3+4, 0.77 for tumor volume≥0.5 ml; without hemorrhage, reader 1, 0.86 for Gleason score≥3+4, 0.88 for tumor volume≥0.5 ml; reader 2, 0.79 for Gleason score≥3+4, 0.83 for tumor volume≥0.5 ml; p > 0.2 for all). Postbiopsy hemorrhage did not negatively affect the detection of clinically significant PZ prostate cancer on multiparametric MR imaging. Advances in knowledge: Under influence of postbiopsy hemorrhage, multiparametric MR can be useful for the detection of clinically significant PZ prostate cancer.

Mechanical disruption of the blood-brain barrier following experimental concussion.

Although concussion is now recognized as a major health issue, its non-lethal nature has limited characterization of the underlying pathophysiology. In particular, potential neuropathological changes have typically been inferred from non-invasive techniques or post-mortem examinations of severe traumatic brain injury (TBI). Here, we used a swine model of head rotational acceleration based on human concussion to examine blood-brain barrier (BBB) integrity after injury in association with diffuse axonal injury and glial responses. We then determined the potential clinical relevance of the swine concussion findings through comparisons with pathological changes in human severe TBI, where post-mortem examinations are possible. At 6-72h post-injury in swine, we observed multifocal disruption of the BBB, demonstrated by extravasation of serum proteins, fibrinogen and immunoglobulin-G, in the absence of hemorrhage or other focal pathology. BBB disruption was observed in a stereotyped distribution consistent with biomechanical insult. Specifically, extravasated serum proteins were frequently observed at interfaces between regions of tissue with differing material properties, including the gray-white boundary, periventricular and subpial regions. In addition, there was substantial overlap of BBB disruption with regions of axonal pathology in the white matter. Acute perivascular cellular uptake of blood-borne proteins was observed to be prominent in astrocytes (GFAP-positive) and neurons (MAP-2-positive), but not microglia (IBA1-positive). Parallel examination of human severe TBI revealed similar patterns of serum extravasation and glial uptake of serum proteins, but to a much greater extent than in the swine model, attributed to the higher injury severity. These data suggest that BBB disruption represents a new and important pathological feature of concussion.

Clinical Reasoning: An unusual cause of adult cryptogenic ischemic stroke

A 60-year-old woman, a nonsmoker, with medical history of hypertension and chronic back pain, presented with sudden-onset left-sided weakness and facial droop to an outside hospital with symptoms of approximately 1 hour duration. Her NIH Stroke Scale (NIHSS) score, a validated tool to quantitatively measure stroke severity,1 was 17, significant for a right gaze preference, left-sided hemiparesis, and left-sided neglect. Her initial head CT demonstrated an Alberta Stroke Programme Early CT Score (ASPECTS) of 9. ASPECTS is a 10-point quantitative CT scan topography score used to measure ischemic changes on head CT.2 The patient's head CT demonstrated subtle right basal ganglia ischemic involvement and an absence of hemorrhage. IV tissue plasminogen activator (tPA) was administered and CT angiography of the head and neck was performed, demonstrating a right middle cerebral artery (MCA) (M1) occlusion. Our institution was consulted as per protocol for ischemic strokes associated with large artery occlusion and she was transferred for potential intra-arterial (IA) thrombectomy. Upon arrival, the patient was mildly lethargic but attended to the examination; she was able to follow simple commands to open/close her eyes and make a fist. The patient was dysarthric, but with time, answered questions appropriately. She had left-sided facial weakness and right gaze preference but was able to cross midline. She demonstrated left-sided neglect to visual and tactile stimuli and was slow to move her left extremities to repeated command, with decreased left-sided extremity strength rated 4/5. NIHSS upon arrival to our institution was 9.

Effects of Mikania glomerata Leaf Extract on Experimental Bothropoides jararaca Envenomation in Wistar Rats

Background: Bothropic envenomation represents the most common ophidic accident worldwide, compared to other snakebites of medical interest. Bothropic venom has proteolytic, vasculotoxic, clotting and/or hemorrhagic actions in animals and humans. Mikania glomerata is a plant found in the Brazilian Atlantic Forest with interesting medical properties that may be useful in ameliorating the effects of ophidic venom, and thus, improving response and outcome. Although Mikania is known to act through inhibition of cytolysins in the venom, there is a lack of consistent research data. The aim of this study was to evaluate the effect of M. glomerata in bothropic envenomation treatment.Materials, Methods &amp; Results: Clinical, hematological, biochemical, and histopathological evaluations were performed following Bothropoides jararaca experimental envenomation in three groups of 18 Wistar rats each. Group VS was inoculated in the pelvic limb via intramuscular injection of bothropic venom and received specific anti-venom serum via intraperitoneal injection. Group VSM was similarly inoculated; it received anti-venom serum and a 10% aqueous extract of the Mikania glomerata plant orally. Group C was the control group and received saline solution alone. Evaluations were performed at 0.5 h (M1), 6 h (M2), and 24 h (M3) after venom inoculation. Animals from both inoculated groups (VS and VSM) showed significant clinical alterations (P &lt; 0.05) manifested as discomfort, uneasiness, pain, and severe edema compared to control animals. Animals from inoculated groups also exhibited statistically significant leukocytosis with neutrophilia, and elevation of blood urea nitrogen and creatine kinase until 6 h after inoculation (P &lt; 0.05 compared to control animals). An acute drop in body temperature was observed 6 h after inoculation (P &lt; 0.05). High levels of creatinine were observed at 6 and 24 h, and plasma protein reduction at almost all evaluation time points (P &lt; 0.05) in both groups compared to that in control. Histopathological evaluation of venom-inoculated animals (groups VS and VSM) showed significant renal hydropic degeneration, acute tubular necrosis, congestion, and hemorrhage (P &lt; 0.05 compared to control). In contrast, animals administered plant extract in addition to anti-venom (group VSM) showed milder muscular fiber regeneration and absence of hemorrhage in the inoculated limb, compared to those that received anti-venom alone (group VS). Overall, there were no statistically significant differences between the inoculated groups (P &gt; 0.05) in terms of edema reduction, pain relief, hematological, biochemical, or histopathological alterations.Discussion: Clinical envenomation symptoms can be explained based on previous reports of bothropic events, where cytolysins such as hyaluronidase, phospholipase A2, and esterases are associated with alterations in cell membrane permeability and release of vasoactive agents. Rhabdomyolysis and muscular necrosis are the main causes of muscular and renal alterations in inoculated groups. M. glomerata extract is known to exert its inhibitory effects on vasoactive and lytic compounds responsible for muscular necrosis. However, some authors have reported only partial effectiveness of Mikania in inactivating bothropic toxins, in contrast with its greater inhibitory action on crotalic venoms. Further studies are necessary for detailed exploration of the properties of Mikania glomerata extract in order to integrate it into supportive measures for snakebite treatments in tropical and subtropical countries.

Lack of chronic neuroinflammation in the absence of focal hemorrhage in a rat model of low-energy blast-induced TBI

Blast-related traumatic brain injury (TBI) has been a common cause of injury in the recent conflicts in Iraq and Afghanistan. Blast waves can damage blood vessels, neurons, and glial cells within the brain. Acutely, depending on the blast energy, blast wave duration, and number of exposures, blast waves disrupt the blood-brain barrier, triggering microglial activation and neuroinflammation. Recently, there has been much interest in the role that ongoing neuroinflammation may play in the chronic effects of TBI. Here, we investigated whether chronic neuroinflammation is present in a rat model of repetitive low-energy blast exposure. Six weeks after three 74.5-kPa blast exposures, and in the absence of hemorrhage, no significant alteration in the level of microglia activation was found. At 6 weeks after blast exposure, plasma levels of fractalkine, interleukin-1β, lipopolysaccharide-inducible CXC chemokine, macrophage inflammatory protein 1α, and vascular endothelial growth factor were decreased. However, no differences in cytokine levels were detected between blast-exposed and control rats at 40 weeks. In brain, isolated changes were seen in levels of selected cytokines at 6 weeks following blast exposure, but none of these changes was found in both hemispheres or at 40 weeks after blast exposure. Notably, one animal with a focal hemorrhagic tear showed chronic microglial activation around the lesion 16 weeks post-blast exposure. These findings suggest that focal hemorrhage can trigger chronic focal neuroinflammation following blast-induced TBI, but that in the absence of hemorrhage, chronic neuroinflammation is not a general feature of low-level blast injury.

Successful intravenous thrombolysis for ischemic stroke after reversal of dabigatran anticoagulation with idarucizumab: a case report

BackgroundNon-vitamin K antagonist oral anticoagulants, including dabigatran, are currently widely used for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. Recently, idarucizumab, a monoclonal antibody fragment for immediate reversal of dabigatran-induced anticoagulation, has been introduced into the market to be used in life-threatening bleeding or urgent surgery, allowing for rapid normalization of clotting parameters. The use of idarucizumab is not yet well established in patients presenting with acute ischemic stroke on dabigatran who are candidates for thrombolytic therapy.Case presentationWe report the case of a 71-year-old hypertensive Caucasian woman with non-valvular atrial fibrillation treated with dabigatran 150 mg twice daily, who presented with acute ischemic stroke causing right-sided hemiparesis and aphasia. Two hours after presentation to the emergency department, a decision was made to administer idarucizumab for achieving complete reversal of any potential anticoagulant effect of dabigatran and, in the absence of any contraindications, our patient underwent successful thrombolysis. At discharge, our patient was able to walk unassisted and had only residual aphasia. Twenty days later, she had completely recovered motor function of her right side, with further progressive improvement of aphasia. Repeat cranial computed tomography confirmed the absence of hemorrhage, and anticoagulant therapy with dabigatran 150 mg twice daily was resumed.ConclusionsOur case report adds to the evidence that idarucizumab administration is safe in the setting of patients with atrial fibrillation treated with dabigatran who develop acute ischemic stroke requiring thrombolysis.

Is ellipsoid zone integrity essential for visual recovery in myopic neovascularization after anti-VEGF therapy?

To evaluate functional prognostic factors and neuroretinal changes after anti-vascular endothelial growth factor (VEGF) treatment in patients with naïve, recent myopic neovascularization (mCNV), as assessed by spectral-domain optical coherence tomography (SD-OCT). Specific changes in tomographic features between baseline and final follow-up were retrospectively evaluated by two examiners independently. Imaging was obtained by a multi-modal imaging system which combines fluorescein angiography and SD-OCT. Twenty-two eyes (male, six; female, 16; mean age, 65±14years) were considered. Mean follow-up was 21.5±14months. Best-corrected visual acuity (BCVA) improved from 0.38±0.26 to 0.16±0.20 logMAR (p<0.001). The ellipsoid zone and the external limiting membrane (ELM) were disrupted in 21 (95.5%) and 15 (68.2%) eyes at baseline, and in 16 (72.7%) and nine (40.9%) eyes after therapy respectively. The ellipsoid zone and ELM were typically intact at lesion margins in 13 (59.1%) and 19 eyes (86.5%) respectively at baseline. The inner retina was intact in 20 eyes (91%). Six eyes (27.3%) exhibited complete regression without fibrosis. Absence of hemorrhage and integrity of lesion-adjacent ELM and of lesion-adjacent ellipsoid zone at baseline were factors for better final BCVA (p≤0.05) CONCLUSION: Vision gain might occur despite ellipsoid zone or ELM restoration. Hemorrhage could be considered a negative prognostic factor, integrity of lesion-adjacent ELM and of lesion-adjacent ellipsoid zone as positive prognostic factors. Myopic CNV can also resolve completely without fibrosis.

Angiographic Analysis of Vascular Integrity After Percutaneous Closure Using Prostar XL Device During Transcatheter Aortic Valve Implantation.

Percutaneous closure devices are commonly used to achieve hemostasis during endovascular procedures including transcatheter aortic valve implantation (TAVI). The aim of our study was to investigate the quality of the percutaneous femoral arterial closure by Prostar XL device using a systematic peroperative angiographic control at the end of TAVI procedure. Two hundred seventeen consecutive patients (mean age: 84 [6.5]; 112 women and 105 men) undergoing TAVI with percutaneous transfemoral access were prospectively registered in our center. Preoperative computed tomography scan was performed, and mean femoral vessel diameter was 7.9 (0.9) mm. At the end of TAVI intervention, the hemostasis was systematically achieved using the percutaneous closure device Prostar XL, without selection of patients based on anatomical criteria. An angiography with front and oblique views was performed to evaluate the quality and the safety of the closure device. Success of the percutaneous closure was defined as the absence of hemorrhage and the restitution of the arterial anatomy. Complications related to the percutaneous closure were classified as stenosis, dissection at the puncture site, suture failure, misplacement, or persistent bleeding. Twenty-three (10.6%) patients had complications related to arterial percutaneous closure-14 (60.8%) stenosis, 6 (26.1%) persistent bleeding, and 1 (4.3%) dissection. These lesions were accessible to endovascular treatment via a crossover procedure. One (4.3%) suture failure and 1 (4.3%) misplacement of the device, with a puncture site created above the femoral arch, were reported. The patient developed a retroperitoneal hematoma postoperatively and required transfusion of 2 units of red blood cells associated with a cutdown to remove hematoma and to repair the common femoral artery. Angiography after arterial percutaneous closure using Prostar XL device during TAVI allows detection and endovascular treatment of vascular complications and is associated with low rate of conversion to open surgery.

Abstract TP177: Long-term Stroke Risk in Patients Diagnosed with Hypertensive Encephalopathy

Introduction: The long-term cerebrovascular consequences of hypertensive encephalopathy (HE) are poorly understood. Therefore, we aimed to measure the risk of stroke following HE. Methods: We identified all adult patients discharged from nonfederal acute care hospitals between 2005 and 2013 in New York with a primary ICD-9-CM discharge diagnosis of HE (437.2). Only patients who underwent magnetic resonance imaging were included to reduce the likelihood of misclassification error. Patients with all other forms of hypertension (401-405), without concomitant codes for HE or cerebrovascular disease (430-438), served as controls. The primary outcome was incident stroke (431, 433.x1, 434.x1, or 436 in the absence of hemorrhage, trauma, or rehabilitation codes). Kaplan-Meier survival analysis was used to calculate cumulative rates of incident stroke and Cox proportional hazards analysis was used to determine the association between HE and incident stroke while adjusting for demographics, vascular risk factors, and the Elixhauser comorbidity index. Results: We identified 1,386 patients with HE and 2,869,873 with hypertension. Over a mean follow-up period of 3.3 (+/-1.8) years, we identified 66,594 ischemic and 12,343 hemorrhagic strokes. After 5 years, the cumulative rate of stroke was 7.8% (95% CI, 6.2-9.9%) in patients with HE and 3.2% (95% CI, 3.2-3.2%; P&lt;0.001 for the log-rank test) in patients with any other hypertensive disease. After adjusting for demographics, vascular risk factors, and the Elixhauser comorbidity index, HE was independently associated with incident stroke (hazard ratio, 1.9; 95% CI, 1.5-2.4) as compared to controls. This association was similar when considering ischemic and hemorrhagic stroke separately. Conclusions: Patients discharged after HE face a higher long-term risk of subsequent stroke than patients without prior neurological complications of hypertension.