Avaliação hemodinâmica de duas vias de reposição volêmica em um modelo de hemorragia da veia cava caudal em porcos

Introdução: A reposição volêmica em pacientes traumatizados tem sido controvérsa. O A.T.L.S. recomenda a infusão de um grande volume de fluidos na fase inicial de tratamento, enquanto outros autores recomendam a administração somente quando do controle da hemorragia. O acesso venoso femoral é contra indicado em pacientes com trauma abdominal por temor de aumento de hemorragia. A solução hipertônica de NaCl a 7,5% (SH) possui benefícios consideráveis de logística e de recuperação hemodinâmica com pequenos volumes de infusão, semelhante as vantagens das soluções padrões isotônicas na fase pré-hospitalar. Objetivos: Criar um modelo de choque hemorrágico induzido por trauma venoso. Avaliar a hemodinâmica e o volume de hemorragia abdominal nos animais submetidos a choque hemorrágico e tratados com SH via acesso femoral e jugular. Métodos: Em 18 porcos da raça landrace, divididos em 3 grupos de 6 animais (Controle, Jugular e Femoral), foi induzido um choque hipovolêmico não controlado pela ruptura da veia cava caudal. Os animais do grupo controle (GC) foram observados por 40 minutos quanto ao seu padrão hemodinâmico de Pressão de Artéria Pulmonar (PAP), Pressão Artérial Média (PAM), Débito Cardíaco (DC) e Fluxo de Veia Porta (FVP), porém sem reposição volêmica. Os animais dos grupos Femoral (GC) e Jugular (GJ) foram tratados com 4 ml/Kg de solução hipertônica de NaCl a 7,5% (SH) aos 20 minutos de experimento. Ao final do experimento, o volume de hemorragia abdominal foi mensurado.Resultados: O grupo controle (GC) apresentou queda dos valores hemodinâmicos aos 10 minutos e estes permaneceram estáveis até o final do experimento. Os animais dos grupos tratamento (GF e GJ) apresentaram melhora da hemodinâmica aos 30 minutos, sem aumento da hemorragia abdominal. Conclusão: A solução hipertônica de NaCl (SH) permitiu a melhora parcial da hemodinâmica no modelo de choque hipovolêmico, sem aumento da hemorragia, independentemente do acesso utilizada para a infusão.

Compressão pneumática intermitente na prevenção de trombose venosa profunda em pacientes cirúrgicos: revisão sistemática e metanálise

Introdução: Trombose Venosa Profunda (TVP) é o resultado de inúmeros fatores, incluindo estase venosa, injuria endotelial e hipercoagulação do sangue. O embolismo pulmonar é a maior complicação da TVP e ocorre quando um trombo ou um coágulo sangüíneo desloca-se em direção aos pulmões. O tromboembolismo é um sério problema de saúde e é responsável por um considerável número de mortes súbitas e por significantes custos de hospitalizações em todo o mundo. Entre os métodos profiláticos usados na prevenção da TVP, há os classificados como mecânicos e os farmacológicos. Ambos são efetivos e podem ser usados sempre que necessário, tendo sido recomendados por consenso internacional. Objetivos: Avaliar a incidência da TVP em pacientes cirúrgicos através da Compressão pneumática Intermitente CPI (coxa/perna ou perna/pé) contra nenhuma forma de profilaxia ou contra fármacos. Métodos: Revisão sistemática de ensaios clínicos randomizados, utilizando a metodologia Cochrane, através de buscas eletrônica e manual. Foram incluídos pacientes cirúrgicos, de ambos os sexos, cuja intervenção foi o uso de aparelhos de compressão pneumática intermitente. Resultados: 4269 pacientes cirúrgicos investigados por 31 ensaios submetidos a um número de intervenções cirúrgicas, incluindo cirurgia ortopédica (joelho e quadris), geral, ginecológica, urológica e neurológica. Dados combinados demonstraram efeitos de tratamento virtualmente iguais entre CPI e abordagens farmacológicas [0.95 (95%CI 0.82, 1.10)], em relação à incidência de TVP. Entretanto, o risco de hemorragia foi maior e estatisticamente significante em pacientes tratados com intervenções farmacológicas [0.37(95%CI 0.20, 0.69)]. Conclusão: Comparações entre as estratégias farmacológicas e mecânicas indicam que ambas são similares na prevenção de trombose venosa profunda. Entretantio, a evidência atual suportaria a escolha das abordagens mecâncias, uma vez que o risco de eventos hemorrágicos favorece os métodos mecânicos.

The vulnerable carotid plaque. Identification of endothelial markers predictive of plaque weakness, rupture predisposition and neoangiogenesis

Background. Neoangiogenesis is crucial in plaque progression and instability. Previous data from our group demonstrated that intra-plaque neovessels show both a Nestin+/WT+ and a Nestin+/WT1- phenotype, the latter being correlated with complications and plaque instability. Aims. The aims of the present thesis are: (i) to confirm our previous results on Nestin/WT1 phenotype in a larger series of carotid atheromatous plaques, (ii) to evaluate the relationship between the Nestin+/WT1- neoangiogenesis phenotype and plaque morphology, (iii) to evaluate the relationship between the immunohistochemical and histopathological characteristics and the clinical instability of the plaques. Materials and Methods. Seventy-three patients (53 males, 20 females, mean age 71 years) were consecutively enrolled. Symptoms, brain CT scan, 14 histological variables, including intraplaque hemorrhage and diffuse calcifications, were collected. Immunohistochemistry for CD34, Nestin and WT1 was performed. RT-PCR was performed to evaluate Nestin and WT1 mRNA (including 5 healthy arteries as controls). Results. Diffusely calcified plaques (13 out of 73) were found predominantly in females (P=0.017), with a significantly lower incidence of symptoms (TIA/stroke) and brain focal lesions (P=0.019 and P=0.013 respectively) than not-calcified plaques, but with the same incidence of intraplaque complications (P=0.156). Accordingly, both calcified and not calcified plaques showed similar mean densities of positivity for CD34, Nestin and WT1. The density of Nestin and WT1 correlated with the occurrence of intra-plaque hemorrhage in all cases, while the density of CD34 correlated only in not-calcified plaques. Conclusions. We confirmed that the Nestin+/WT1- phenotype characterizes the neovessels of instable plaques, regardless the real amount of CD34-positive neoangiogenesis. The calcified plaques show the same incidence of histological complications, albeit they do not influence symptomatology and plaque vulnerability. Female patients show a much higher incidence of not-complicated or calcified plaques, receiving de facto a sort of protection compared to male patients.

Valutazione di marker diagnostici, epidemiologia e nuove prospettive terapeutiche nell' avvelenamento da rodenticidi anticoagulanti nel cane.

In Medicina Veterinaria l'avvelenamento da rodenticidi anticoagulanti è conosciuto e studiato ormai da anni, essendo una delle intossicazioni più comunemente riscontrate nelle specie non target. In letteratura si rinvengono numerose pubblicazioni ma alcuni aspetti sono rimasti ancora inesplorati.Questo studio si propone di valutare il processo infiammatorio, mediante le proteine di fase acuta (APPs), in corso di fenomeni emorragici, prendendo come modello reale un gruppo di soggetti accidentalmente avvelenati da rodenticidi anticoagulanti. I 102 soggetti avvelenati presentano un valore più elevato di proteina C reattiva (CRP)con una mediana di 4.77 mg/dl statisticamente significativo rispetto alla mediana delle due popolazioni di controllo di pari entità numerica create con cross match di sesso, razza ed età; rispettivamente 0.02 mg/dl dei soggetti sani e 0.37 mg/dl dei soggetti malati di altre patologie. Inoltre all'interno del gruppo dei soggetti avvelenati un valore di CRP elevato all'ammissione può predisporre al decesso. La proteina C reattiva assume quindi un ruolo diagnostico e prognostico in questo avvelenamento. Un'altra finalità, di non inferiore importanza, è quella di definire una linea guida terapeutica con l'ausilio di biomarker coagulativi e di valutare la sicurezza della vitamina K per via endovenosa: in 73 cani, non in terapia con vitamina k, intossicati da rodenticidi anticoagulanti, i tempi della coagulazione (PT ed aPTT) ritornano nel range di normalità dopo 4 ore dalla prima somministrazione di 5 mg/kg di vitamina k per via endovenosa e nessun soggetto durante e dopo il trattamento ha manifestato reazioni anafilattiche, nessuno dei pazienti ha necessitato trasfusione ematica e tutti sono sopravvissuti. Infine si è valutata l'epidemiologia dell'ingestione dei prodotti rodenticidi nella specie oggetto di studio e la determinazione dei principi attivi mediante cromatografia liquida abbinata a spettrofotometria di massa (UPLC-MS/MS).

Rapid spontaneous malignant progression of supratentorial tanycytic ependymoma with sarcomatous features - "Ependymosarcoma"

By analogy to gliosarcoma, the term "ependymosarcoma" has recently been coined to thematize the rare phenomenon of a malignant mesenchymal component arising within an ependymoma. We report on an example of this paradigm, involving tanycytic ependymoma as the host tumor in a 40-year-old female who underwent two tumor extirpation procedures at one-year interval. She first presented with severe headaches, and was seen by imaging to harbor a moderately enhancing mass 2.5cm in diameter at the rostral septum pellucidum accompanied by occlusive hydrocephalus. Microscopically, the tumor consisted of solid, wavy fascicles of elongated cells that were occasionally interrupted by vague perivascular pseudorosettes. Mitotic activity was absent, and less than 1% of nuclei immunoreacted for MIB-1. A histological diagnosis of tanycytic ependymoma (WHO grade II) was rendered, and no adjuvant therapy given. At recurrence, the lesion was 3.5cm in diameter, intensely enhancing, and had already seeded into the subarachnoid space. Histology showed a biphasic glial-sarcomatous architecture with remnants of the original ependymoma now displaying hypercellularity and atypical - yet not frankly anaplastic - features. The sarcomatous moiety consisted of spindle and epithelioid cells densely interwoven with reticulin fibers. While the ependymal component was GFAP and S100 protein positive, and featured punctate staining for EMA, none of these markers was expressed in the adjacent sarcoma. Instead, the latter reacted for vimentin and smooth muscle actin. To the best of our knowledge, this is the first documentation of tanycytic ependymoma undergoing malignant transformation, one driven by a highly anaplastic mesenchymal component, corresponding to "ependymosarcoma".

Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function

Severe hereditary coagulation factor XIII deficiency is a rare homozygous bleeding disorder affecting one person in every two million individuals. In contrast, heterozygous factor XIII deficiency is more common, but usually not associated with severe hemorrhage such as intracranial bleeding or hemarthrosis. In most cases, the disease is caused by F13A gene mutations. Causative mutations associated with the F13B gene are rarer.

Brain herniation in a patient with apparently normal intracranial pressure: a case report

Introduction Intracranial pressure monitoring is commonly implemented in patients with neurologic injury and at high risk of developing intracranial hypertension, to detect changes in intracranial pressure in a timely manner. This enables early and potentially life-saving treatment of intracranial hypertension. Case presentation An intraparenchymal pressure probe was placed in the hemisphere contralateral to a large basal ganglia hemorrhage in a 75-year-old Caucasian man who was mechanically ventilated and sedated because of depressed consciousness. Intracranial pressures were continuously recorded and never exceeded 17 mmHg. After sedation had been stopped, our patient showed clinical signs of transtentorial brain herniation, despite apparently normal intracranial pressures (less than 10 mmHg). Computed tomography revealed that the size of the intracerebral hematoma had increased together with significant unilateral brain edema and transtentorial herniation. The contralateral hemisphere where the intraparenchymal pressure probe was placed appeared normal. Our patient underwent emergency decompressive craniotomy and was tracheotomized early, but did not completely recover. Conclusions Intraparenchymal pressure probes placed in the hemisphere contralateral to an intracerebral hematoma may dramatically underestimate intracranial pressure despite apparently normal values, even in the case of transtentorial brain herniation.

Clinical radiology and postmortem imaging (Virtopsy) are not the same: Specific and unspecific postmortem signs

The aim of this article is to disclose the characteristics of postmortem forensic imaging; give an overview of the several possible findings in postmortem imaging, which are uncommon or new to clinical radiologists; and discuss the possible pitfalls. Unspecific postmortem signs are enlisted and specific signs shall be presented, which are typical for one cause of death. Unspecific signs. Livor mortis may not only be seen from the outside, but also inside the body in the lungs: in chest CT internal livor mortis appear as ground glass opacity in the dependent lower lobes. The aortic wall is often hyperdense in postmortem CT due to wall contraction and loss of luminal pressure. Gas bubbles are very common postmortem due to systemic gas embolism after major open trauma, artificial respiration or initial decomposition; in particular putrefaction produces gas bubbles globally. Specific signs. Intracranial bleeding is hyperattenuating both in radiology and in postmortem imaging. Signs of strangulation are hemorrhage in the soft tissue of the neck like skin, subcutaneous tissue, platysma muscle and lymph nodes. The "vanishing" aorta is indicative for exsanguination. Fluid in the airways with mosaic lung densities and emphysema (aquosum) is typical for fresh-water drowning.

Fatal thoracic impalement on postmortem imaging

In the present paper, the authors describe a case of fatal thoracic impalement in a victim of a road traffic accident, by penetration of a metal handrail. The driver lost control of his car while overtaking three cars. Due to the force of the vehicle collision with a metal railing, the upper cross bar penetrated the front of the car and subsequently the driver was pierced by the center-pillar in the car. Death occurred at the scene of the accident. Postmortem, computed tomography, computed tomography angiography and a magnetic resonance tomography were performed and revealed severe heart destruction and hemorrhage as cause of death. The present case report shows that postmortem imaging might have value as a screening method to decide whether arising forensic questions can be answered just by imaging like in the presented case or if further examinations such as conventional autopsy are required.

Focal cystic high-attenuation lesions: characterization in renal phantom by using photon-counting spectral CT--improved differentiation of lesion composition

To evaluate the capability of spectral computed tomography (CT) to improve the characterization of cystic high-attenuation lesions in a renal phantom and to test the hypothesis that spectral CT will improve the differentiation of cystic renal lesions with high protein content and those that have undergone hemorrhage or malignant contrast-enhancing transformation.

Genome-wide association study of intracranial aneurysm identifies three new risk loci

Saccular intracranial aneurysms are balloon-like dilations of the intracranial arterial wall; their hemorrhage commonly results in severe neurologic impairment and death. We report a second genome-wide association study with discovery and replication cohorts from Europe and Japan comprising 5,891 cases and 14,181 controls with approximately 832,000 genotyped and imputed SNPs across discovery cohorts. We identified three new loci showing strong evidence for association with intracranial aneurysms in the combined dataset, including intervals near RBBP8 on 18q11.2 (odds ratio (OR) = 1.22, P = 1.1 x 10(-12)), STARD13-KL on 13q13.1 (OR = 1.20, P = 2.5 x 10(-9)) and a gene-rich region on 10q24.32 (OR = 1.29, P = 1.2 x 10(-9)). We also confirmed prior associations near SOX17 (8q11.23-q12.1; OR = 1.28, P = 1.3 x 10(-12)) and CDKN2A-CDKN2B (9p21.3; OR = 1.31, P = 1.5 x 10(-22)). It is noteworthy that several putative risk genes play a role in cell-cycle progression, potentially affecting the proliferation and senescence of progenitor-cell populations that are responsible for vascular formation and repair.

Vasculitides associated with IgG antineutrophil cytoplasmic autoantibodies in childhood

Immunoglobulin (Ig)G antineutrophil cytoplasmic autoantibodies are causally associated with necrotizing vasculitides that are characterized immunopathologically by little or no deposition of immunoreactants, such as Wegener granulomatosis, microscopic polyangiitis, Churg-Strauss angiitis, "renal-limited" vasculitis and a number of drug-induced vasculitides. Clinical routine testing targets the antigens myeloperoxidase and proteinase 3. However, in all of the conditions mentioned, the renal histopathologic findings are indistinguishable. Churg-Strauss angiitis (characterized by necrotizing vasculitis, granulomatous inflammation and tissue eosinophilia), Wegener granulomatosis (characterized by necrotizing vasculitis and granulomatous inflammation) and microscopic polyangiitis (characterized by necrotizing vasculitis) often present with fever, weight loss and a multisystem involvement (ear, nose, throat, lung, eyes, peripheral nerve and heart). Fifty years ago these conditions were very often fatal within 6 months of diagnosis. The introduction of corticosteroids and cyclophosphamide has resulted in a dramatic clinical benefit. Patients who develop treatment-related morbidity can be switched from cyclophosphamide to azathioprine after achieving remission. In patients with less severe disease, methotrexate achieves remission with a success rate similar to that of cyclophosphamide. Plasma exchange, in association with immunosuppression, is likely to be a beneficial therapy for patients with severe kidney disease or pulmonary hemorrhage.

Combined use of pulsed arterial spin-labeling and susceptibility-weighted imaging in stroke at 3T

Background and Purpose: In acute stroke it is no longer sufficient to detect simply ischemia, but also to try to evaluate reperfusion/recanalization status and predict eventual hemorrhagic transformation. Arterial spin labeling (ASL) perfusion may have advantages over contrast-enhanced perfusion-weighted imaging (cePWI), and susceptibility weighted imaging (SWI) has an intrinsic sensitivity to paramagnetic effects in addition to its ability to detect small areas of bleeding and hemorrhage. We want to determine here if their combined use in acute stroke and stroke follow-up at 3T could bring new insight into the diagnosis and prognosis of stroke leading to eventual improved patient management. Methods: We prospectively examined 41 patients admitted for acute stroke (NIHSS >1). Early imaging was performed between 1 h and 2 weeks. The imaging protocol included ASL, cePWI, SWI, T2 and diffusion tensor imaging (DTI), in addition to standard stroke protocol. Results: We saw four kinds of imaging patterns based on ASL and SWI: patients with either hypoperfusion and hyperperfusion on ASL with or without changes on SWI. Hyperperfusion was observed on ASL in 12/41 cases, with hyperperfusion status that was not evident on conventional cePWI images. Signs of hemorrhage or blood-brain barrier breakdown were visible on SWI in 15/41 cases, not always resulting in poor outcome (2/15 were scored mRS = 0–6). Early SWI changes, together with hypoperfusion, were associated with the occurrence of hemorrhage. Hyperperfusion on ASL, even when associated with hemorrhage detected on SWI, resulted in good outcome. Hyperperfusion predicted a better outcome than hypoperfusion (p = 0.0148). Conclusions: ASL is able to detect acute-stage hyperperfusion corresponding to luxury perfusion previously reported by PET studies. The presence of hyperperfusion on ASL-type perfusion seems indicative of reperfusion/collateral flow that is protective of hemorrhagic transformation and a marker of favorable tissue outcome. The combination of hypoperfusion and changes on SWI seems on the other hand to predict hemorrhage and/or poor outcome.

Treatment issues in spontaneous cervicocephalic artery dissections

The management of cervicocephalic arterial dissections raises many unsolved issues such as: how to best acutely treat patients who present with ischemic stroke or occasionally with sub-arachnoid hemorrhage? How to best prevent ischemic stroke in patients who present with purely local signs such as headache, painful Horner Syndrome or neck pain? How long and how should patients be treated after cervicocephalic arterial dissections? Can patients resume their sports activities and when? The consensus is that, given the well-established initial thromboembolic risk, an urgent antithrombotic treatment is required in patients with a recent nonhemorrhagic cervicocephalic arterial dissection, but the type of antithrombotic treatment - anticoagulants or aspirin - as well as the indication for a local arterial treatment such as angioplasty/stenting remain debated. Evidence from a randomized clinical trial would be welcome but such a trial raises major issues of methodology, feasibility and funding. Meanwhile, cervicocephalic arterial dissection remains a situation when a bedside clinician should use, on a case-by-case basis, best clinical judgment and adopt a stepped care approach in the minority of patients who deteriorate despite initial treatment.

IV thrombolysis and statins

To examine whether prior statin use affects outcome and intracranial hemorrhage (ICH) rates in stroke patients receiving IV thrombolysis (IVT).