Cerebral Hypoperfusion in Posterior Reversible Encephalopathy Syndrome is Different from Transient Ischemic Attack on CT Perfusion.

BACKGROUND: PRES is a reversible neurotoxic state presenting with headache, altered mental status, visual loss, and seizures. Delayed diagnosis can be avoided if radiological patterns could distinguish PRES from cerebral ischemia. METHODS: Clinical and radiological data were collected on all hospitalized patients who had (1) discharge diagnosis of PRES and (2) acute CTP/CTA. Data were compared with 10 TIA patients with proven cytotoxic edema on MRI. RESULTS: Of the four PRES patients found, three were correlated with acute blood pressure and one with chemotherapy. At the radiological level, quantitative analyses of the CTP parameters showed that 2 out of 4 patients had bilaterally reduced CBF-values (23.2-47.1 ml/100g/min) in occipital regions, as seen in the pathological regions of TIA patients (27.3 ± 13.5 ml/100g/min). When compared with TIA patients, the pathological ROI's demonstrated decreased CBV-values (3.4-5.6 ml/100g). Vasogenic edema on MRI FLAIR imaging was seen in only one PRES patient, and cytotoxic edema on DWI-imaging was never found. CT angiography showed in one PRES patient a vasospasm-like unilateral posterior cerebral artery. CONCLUSIONS: If confirmed by other groups, CTP and CTA imaging in patients with acute visual loss and confusion may help to distinguish PRES from bi-occipital ischemia. These radiological parameters may identify PRES patients at risk for additional tissue infarction.

Local Salmonella immunostimulation recruits vaccine-specific CD8 T cells and increases regression of bladder tumor.

NlmCategory="UNASSIGNED">The efficacy of antitumoral responses can be increased using combinatorial vaccine strategies. We recently showed that vaccination could be optimized by local administration of diverse molecular or bacterial agents to target and augment antitumoral CD8 T cells in the genital mucosa (GM) and increase regression of cervical cancer in an animal model. Non muscle-invasive bladder cancer is another disease that is easily amenable to local therapies. In contrast to data obtained in the GM, in this study we show that intravesical (IVES) instillation of synthetic toll-like receptor (TLR) agonists only modestly induced recruitment of CD8 T cells to the bladder. However, IVES administration of Ty21a, a live bacterial vaccine against typhoid fever, was much more effective and increased the number of total and vaccine-specific CD8 T cells in the bladder approximately 10 fold. Comparison of chemokines induced in the bladder by either CpG (a TLR-9 agonist) or Ty21a highlighted the preferential increase in complement component 5a, CXCL5, CXCL2, CCL8, and CCL5 by Ty21a, suggesting their involvement in the attraction of T cells to the bladder. IVES treatment with Ty21a after vaccination also significantly increased tumor regression compared to vaccination alone, resulting in 90% survival in an orthotopic murine model of bladder cancer expressing a prototype tumor antigen. Our data demonstrate that combining vaccination with local immunostimulation may be an effective treatment strategy for different types of cancer and also highlight the great potential of the Ty21a vaccine, which is routinely used worldwide, in such combinatorial therapies.

Identification of Rare High-Avidity, Tumor-Reactive CD8+ T Cells by Monomeric TCR-Ligand Off-Rates Measurements on Living Cells.

The avidity of the T-cell receptor (TCR) for antigenic peptides presented by the peptide-MHC (pMHC) on cells is a key parameter for cell-mediated immunity. Yet a fundamental feature of most tumor antigen-specific CD8(+) T cells is that this avidity is low. In this study, we addressed the need to identify and select tumor-specific CD8(+) T cells of highest avidity, which are of the greatest interest for adoptive cell therapy in patients with cancer. To identify these rare cells, we developed a peptide-MHC multimer technology, which uses reversible Ni(2+)-nitrilotriacetic acid histidine tags (NTAmers). NTAmers are highly stable but upon imidazole addition, they decay rapidly to pMHC monomers, allowing flow-cytometric-based measurements of monomeric TCR-pMHC dissociation rates of living CD8(+) T cells on a wide avidity spectrum. We documented strong correlations between NTAmer kinetic results and those obtained by surface plasmon resonance. Using NTAmers that were deficient for CD8 binding to pMHC, we found that CD8 itself stabilized the TCR-pMHC complex, prolonging the dissociation half-life several fold. Notably, our NTAmer technology accurately predicted the function of large panels of tumor-specific T cells that were isolated prospectively from patients with cancer. Overall, our results demonstrated that NTAmers are effective tools to isolate rare high-avidity cytotoxic T cells from patients for use in adoptive therapies for cancer treatment.

Choroidal Mast Cells in Retinal Pathology: A Potential Target for Intervention.

Mast cells are important in the initiation of ocular inflammation, but the consequences of mast cell degranulation on ocular pathology remain uncharacterized. We induced mast cell degranulation by local subconjunctival injection of compound 48/80. Initial degranulation of mast cells was observed in the choroid 15 minutes after the injection and increased up to 3 hours after injection. Clinical signs of anterior segment inflammation paralleled mast cell degranulation. With the use of optical coherence tomography, dilation of choroidal vessels and serous retinal detachments (SRDs) were observed and confirmed by histology. Subconjunctival injection of disodium cromoglycate significantly reduced the rate of SRDs, demonstrating the involvement of mast cell degranulation in posterior segment disorders. The infiltration of polymorphonuclear and macrophage cells was associated with increased ocular media concentrations of tumor necrosis factor-α, CXCL1, IL-6, IL-5, chemokine ligand 2, and IL-1β. Analysis of the amounts of vascular endothelial growth factor and IL-18 showed an opposite evolution of vascular endothelial growth factor compared with IL-18 concentrations, suggesting that they regulate each other's production. These findings suggest that the local degranulation of ocular mast cells provoked acute ocular inflammation, dilation, increased vascular permeability of choroidal vessels, and SRDs. The involvement of mast cells in retinal diseases should be further investigated. The pharmacologic inhibition of mast cell degranulation may be a potential target for intervention.

Ocular adnexal (orbital) solitary fibrous tumor: nuclear STAT6 expression and literature review.

PURPOSE: To report the clinico-pathological features of solitary fibrous tumor occurring in the ocular adnexa (OA) in a single center. To assess the presence of NAB2-STAT6 genes fusion in OA solitary fibrous tumor detected by nuclear overexpression of STAT6. METHODS: Retrospective study including orbital and OA solitary fibrous tumors treated between 2006 and 2014 in our center. The clinical, radiological, and histopathological findings were evaluated. STAT6 expression was assessed by immunohistochemistry. RESULTS: Five patients were identified and presented with a chronic OA mass. The tumors were radiologically well delimited, highly vascularized and without bone erosion. All the patients underwent complete surgical excision. Pathological examination confirmed solitary fibrous tumor in all cases. All tumors demonstrated a nuclear expression of STAT6. There were no recurrences, with a mean follow-up of 5 years after surgery. Our review demonstrated that proptosis was the most common presentation occurring in 60 % of the cases. In the ocular adnexa, adverse histological criteria were found in 19.7 % of the tumors, and recurrences were observed in 48 % of these cases. Thirty-six percent of patients presented at least one local recurrence, and metastastic spread was found in 2.4 % of the cases. Tumor-related death was described in two cases. CONCLUSION: Ocular adnexal SFT are rare and usually present as a chronic orbital mass with proptosis. In the OA, solitary fibrous tumor demonstrates STAT6 nuclear expression, as documented in other locations. Recurrences are unusual and metastasis exceptional. Initial surgical resection should be complete in order to avoid recurrence.

Efficacy of tumor necrosis factor inhibitors in patients with ankylosing spondylitis

Objectives: This study aims to investigate the efficacy of tumor necrosis factor-alpha blockers such as infliximab, etanercept, and adalimumab in the treatment of ankylosing spondylitis. Patients and methods: The outcome of tumor necrosis factor-alpha blocker treatment was analyzed retrospectively in 59 patients with ankylosing spondylitis who were being treated in our clinic during last nine years. The patients' Assessment of SpondyloArthritis International Society (ASAS) 20 and ASAS 40 response rates, adverse drugs effects, and treatment compliance were evaluated. Results: ASAS 20 response was achieved by 89.8% of the patients in the third month, and by 93.2% in the sixth month. ASAS 40 response was achieved by 61% of the patients in the third and sixth month. No statistically significant difference was detected between the three tumor necrosis factor-alpha blockers with regards to the ASAS 40 response rates. Mild infections, observed in 31 of the patients, were the most common side effects. Serious side effect was observed in only one patient. The number of patients who withdrew from the treatment for various reasons was six.

Tumor de pequenas células redondas desmoplásico intra-abdominal: relato de caso

Os autores relatam um caso de tumor de pequenas células redondas desmoplásico intra-abdominal acometendo paciente do sexo masculino, de 21 anos de idade, atendido com quadro de dor abdominal, trombose do membro inferior direito e perda da função renal, de causa obstrutiva. A investigação demonstrou volumosa lesão abdominopélvica, sólida, bocelada, com áreas císticas internas, situada posteriormente à bexiga, causando obstrução ureteral, compressão da veia ilíaca direita e oclusão parcial do reto, além de acometimento de linfonodos intra e retroperitoneais. São descritos os achados cirúrgicos, de ultra-sonografia, tomografia computadorizada e ressonância magnética, bem como aqueles do estudo macroscópico, microscopia e imuno-histoquímica.

Tumores ósseos raros da calota craniana: sarcoma de Ewing e tumor de Triton

O sarcoma de Ewing e o tumor de Triton representam dois tumores ósseos raros da calota craniana, os quais possuem clínica e aspecto imagenológico inespecíficos. Entretanto, os métodos de imagem são importantes para a detecção das lesões durante a investigação diagnóstica, para a avaliação da extensão das lesões ósseas, do possível acometimento de partes moles e do parênquima encefálico, e avaliação de recorrência local e/ou metástases a distância. A confirmação diagnóstica é determinada pela histologia e auxiliada pela imuno-histoquímica. Os autores relatam dois casos desses tumores e seus achados pelos métodos de imagem.

Comprometimento órbito-craniano por tumores malignos sinonasais: estudo por tomografia computadorizada

Tumores malignos das cavidades sinonasais são raros e freqüentemente diagnosticados em estágio avançado da doença. A extensão destes tumores para locais críticos como a órbita e o crânio gera dificuldades no tratamento destas lesões. Dez pacientes com neoplasia maligna sinonasal, sem qualquer tratamento prévio e com evidência radiológica de extensão órbito-craniana, foram estudados por tomografia computadorizada. Dos dez tumores, cinco (50%) foram neoplasias epiteliais, tendo sido a mais comum o carcinoma epidermóide (três casos). O sítio de origem tumoral mais comum foi o seio etmoidal, em quatro pacientes (40%), seguido pelo seio maxilar (30%) e pela fossa nasal (30%). Dezesseis órbitas foram comprometidas, já que seis pacientes (60%) apresentaram acometimento orbitário tumoral bilateral. Os tumores se estenderam mais freqüentemente para as órbitas através de erosão da parede medial e do soalho orbitários. A maioria das órbitas teve todos os compartimentos acometidos. Extensão dos tumores para a cavidade craniana foi mais comum através do teto etmoidal (70%) e teto orbitário (30%). A fossa craniana anterior foi acometida em oito casos (80%), seguida pela fossa craniana média (40%) e pelo lobo frontal (excluindo-se a fossa anterior) (30%). Trinta e sete regiões da face foram acometidas pelos dez tumores, excluindo-se o sítio de origem da neoplasia e a região órbito-craniana, corroborando a grande extensão loco-regional do tumor no momento do diagnóstico.