Streptococcal acute pharyngitis

Acute pharyngitis/tonsillitis, which is characterized by inflammation of the posterior pharynx and tonsils, is a common disease. Several viruses and bacteria can cause acute pharyngitis; however, Streptococcus pyogenes (also known as Lancefield group A β-hemolytic streptococci) is the only agent that requires an etiologic diagnosis and specific treatment. S. pyogenes is of major clinical importance because it can trigger post-infection systemic complications, acute rheumatic fever, and post-streptococcal glomerulonephritis. Symptom onset in streptococcal infection is usually abrupt and includes intense sore throat, fever, chills, malaise, headache, tender enlarged anterior cervical lymph nodes, and pharyngeal or tonsillar exudate. Cough, coryza, conjunctivitis, and diarrhea are uncommon, and their presence suggests a viral cause. A diagnosis of pharyngitis is supported by the patient's history and by the physical examination. Throat culture is the gold standard for diagnosing streptococcus pharyngitis. However, it has been underused in public health services because of its low availability and because of the 1- to 2-day delay in obtaining results. Rapid antigen detection tests have been used to detect S. pyogenes directly from throat swabs within minutes. Clinical scoring systems have been developed to predict the risk of S. pyogenes infection. The most commonly used scoring system is the modified Centor score. Acute S. pyogenes pharyngitis is often a self-limiting disease. Penicillins are the first-choice treatment. For patients with penicillin allergy, cephalosporins can be an acceptable alternative, although primary hypersensitivity to cephalosporins can occur. Another drug option is the macrolides. Future perspectives to prevent streptococcal pharyngitis and post-infection systemic complications include the development of an anti-Streptococcus pyogenes vaccine.

The effectiveness of a rotavirus vaccine in preventing hospitalizations and deaths presumably due to acute infectious diarrhea in Brazilian children: a quasi-experimental study

INTRODUCTION: Rotavirus is the main etiologic agent of acute infectious diarrhea in children worldwide. Considering that a rotavirus vaccine (G1P8, strain RIX4414) was added to the Brazilian vaccination schedule in 2006, we aimed to study its effectiveness and safety regarding intestinal intussusception. METHODS: A quasi-experimental trial was performed in which the primary outcome was the number of hospitalizations that were presumably due to acute infectious diarrhea per 100,000 children at risk (0-4 years old). The secondary outcomes included mortality due to acute infectious diarrhea and the intestinal intussusception rates in children in the same age range. We analyzed three scenarios: Health Division XIII of the State of São Paulo (DRS XIII) from 2002 to 2008, the State of São Paulo, and Brazil from 2002 to 2012. RESULTS: The averages of the hospitalization rates for 100,000 children in the pre- and post-vaccination periods were 1,413 and 959, respectively, for DRS XIII (RR=0.67), 312 and 249, respectively, for the State of São Paulo (RR=0.79), and 718 and 576, respectively, for Brazil (RR=0.8). The mortality rate per 100,000 children in the pre- and post-vaccination periods was 2.0 and 1.3, respectively, for DRS XIII (RR=0.66), 5.5 and 2.5, respectively, for the State of São Paulo (RR=0.47), and 15.0 and 8.0, respectively, for Brazil (RR=0.53). The average annual rates of intussusception for 100,000 children in DRS XIII were 28.0 and 22.0 (RR=0.77) in the pre- and post-vaccination periods, respectively. CONCLUSIONS: A monovalent rotavirus vaccine was demonstrated to be effective in preventing the hospitalizations and deaths of children that were presumably due to acute infectious diarrhea, without increasing the risk of intestinal intussusception.

Spatiotemporal analysis of reported cases of acute Chagas disease in the State of Pernambuco, Brazil, from 2002 to 2013

INTRODUCTION: Control strategies to eliminate the transmission of Chagas disease by insect vectors have significantly decreased the number of reported acute cases in Brazil. However, data regarding the incidence and distribution of acute Chagas disease cases in the State of Pernambuco are unavailable in the literature. METHODS: A geographical information system was used to delineate the spatiotemporal distribution profile of the cases from 2002 to 2013 in 185 municipalities of Pernambuco based on the municipality where notification occurred. The results were presented in digital maps generated by the TerraView software (INPE). RESULTS: A total of 302 cases of acute disease were recorded in 37.8% of the municipalities, for a total of 0.13 cases per 1,000,000 inhabitants per year. Out of the 302 cases, 99.3% were reported between 2002 and 2006. The most affected municipalities were Carnaubeira da Penha, Mirandiba and Terra Nova. The risk maps showed a significant decrease in the number of notifications and a concentration of cases in the Midwest region. CONCLUSIONS: This study highlights a significant decrease in new cases of acute Chagas disease in Pernambuco starting in 2006 when Brazil received an international certification for the interruption of vectorial transmission by Triatoma infestans. However, control strategies should still be encouraged because other triatomine species can also transmit the parasite; moreover, other transmission modes must not be neglected.

Acute disseminated encephalomyelitis following inactivated influenza vaccination in the Brazilian Amazon: a case report

AbstractHere, we describe a case of acute disseminated encephalomyelitis (ADEM) that occurred during a plausible risk interval following inactivated influenza vaccination in a previously healthy 27-year-old man from Manaus, Brazil. He was treated with intravenous methylprednisolone and immunoglobulin. One-month follow-up revealed resolution of the brain lesions, but not of the spinal cord lesions. No recurrence or progression of the main neurological symptoms was observed. After two years of monitoring, the patient continues to experience weak lower limbs and urinary retention. Thus, we recommend that ADEM should be considered in a patient presenting with neurological symptoms after influenza vaccination.

Chagas disease in the State of Amazonas: history, epidemiological evolution, risks of endemicity and future perspectives

Chagas disease (CD) is a parasitic infection that originated in the Americas and is caused by Trypanosoma cruzi. In the last few years, the disease has spread to countries in North America, Asia and Europe due to the migration of Latin Americans. In the Brazilian Amazon, CD has an endemic transmission, especially in the Rio Negro region, where an occupational hazard was described for piaçaveiros (piassaba gatherers). In the State of Amazonas, the first chagasic infection was reported in 1977, and the first acute CD case was recorded in 1980. After initiatives to integrate acute CD diagnostics with the malaria laboratories network, reports of acute CD cases have increased. Most of these cases are associated with oral transmission by the consumption of contaminated food. Chronic cases have also been diagnosed, mostly in the indeterminate form. These cases were detected by serological surveys in cardiologic outpatient clinics and during blood donor screening. Considering that the control mechanisms adopted in Brazil's classic transmission areas are not fully applicable in the Amazon, it is important to understand the disease behavior in this region, both in the acute and chronic cases. Therefore, the pursuit of control measures for the Amazon region should be a priority given that CD represents a challenge to preserving the way of life of the Amazon's inhabitants.

Extraction of Trypanosoma cruzi DNA from food: a contribution to the elucidation of acute Chagas disease outbreaks

Abstract: INTRODUCTION: Before 2004, the occurrence of acute Chagas disease (ACD) by oral transmission associated with food was scarcely known or investigated. Originally sporadic and circumstantial, ACD occurrences have now become frequent in the Amazon region, with recently related outbreaks spreading to several Brazilian states. These cases are associated with the consumption of açai juice by waste reservoir animals or insect vectors infected with Trypanosoma cruzi in endemic areas. Although guidelines for processing the fruit to minimize contamination through microorganisms and parasites exist, açai-based products must be assessed for quality, for which the demand for appropriate methodologies must be met. METHODS: Dilutions ranging from 5 to 1,000 T. cruzi CL Brener cells were mixed with 2mL of acai juice. Four Extraction of T. cruzi DNA methods were used on the fruit, and the cetyltrimethyl ammonium bromide (CTAB) method was selected according to JRC, 2005. RESULTS: DNA extraction by the CTAB method yielded satisfactory results with regard to purity and concentration for use in PCR. Overall, the methods employed proved that not only extraction efficiency but also high sensitivity in amplification was important. CONCLUSIONS: The method for T. cruzi detection in food is a powerful tool in the epidemiological investigation of outbreaks as it turns epidemiological evidence into supporting data that serve to confirm T. cruzi infection in the foods. It also facilitates food quality control and assessment of good manufacturing practices involving acai-based products.

Vaccine-associated paralytic Poliomyelitis: a case report of domiciliary transmission

Poliomyelitis associated with live strain vaccine is defined as the paralytic form of the acute anterior poliomyelitis related to the vaccine strain. Since these strains behave similarly to the wild-type virus, we can differentiate, epidemiologically, two types of vaccine-associated poliomyelitis: cases in which the patient was vaccinated and cases in which the patient had had contact with vaccinated individuals. We herein present the case of an unvaccinated child, with a clinical picture of an acute anterior poliomyelitis associated with the live strain vaccine, whose brother received the Sabin vaccine 20 days before the onset of the symptoms. Vaccine strain of the type 3 poliovirus was isolated in fecal culture and a presented mutation in nucleotide 472 (C®U) in the 5' non-coding region, which is strongly related to the higher strain virulence.

Invasive enteritis by Strongyloides stercoralis presenting as acute abdominal distress under corticosteroid therapy

Overwhelming helminthiasis is still a problem in endemic areas, especially in immunocompromised patients. We report a case of invasive intestinal strongyloidiasis that was clinically expressed as acute abdominal distress in a 73-year-old man from São Paulo who had been receiving methylprednisone, 20 mg/day, for one year for osteoarthritis. A surgical specimen from the ileum revealed invasive enteritis with severe infestation by Strongyloides stercoralis. The patient died of sepsis 6 days after surgery. The possibility of invasive strongyloidiasis should be considered in the differential diagnosis of acute abdominal distress in patients undergoing immunosuppressive therapy.

Acute renal failure due to abdominal compartment syndrome: report on four cases and literature review

We report on 4 cases of abdominal compartment syndrome complicated by acute renal failure that were promptly reversed by different abdominal decompression methods. Case 1: A 57-year-old obese woman in the post-operative period after giant incisional hernia correction with an intra-abdominal pressure of 24 mm Hg. She was sedated and curarized, and the intra-abdominal pressure fell to 15 mm Hg. Case 2: A 73-year-old woman with acute inflammatory abdomen was undergoing exploratory laparotomy when a hypertensive pneumoperitoneum was noticed. During the surgery, enhancement of urinary output was observed. Case 3: An 18-year-old man who underwent hepatectomy and developed coagulopathy and hepatic bleeding that required abdominal packing, developed oliguria with a transvesical intra-abdominal pressure of 22 mm Hg. During reoperation, the compresses were removed with a prompt improvement in urinary flow. Case 4: A 46-year-old man with hepatic cirrhosis was admitted after incisional hernia repair with intra-abdominal pressure of 16 mm Hg. After paracentesis, the intra-abdominal pressure fell to 11 mm Hg.

Pancreatic lesions in acute experimental Chagas' disease

BACKGROUND: Chagas' disease is an endemic tropical affliction found from southern United States to Argentina. The acute phase of this disease is difficult to study in man because the symptoms are non-specific and most cases require no medical assistance. Experimental models have been developed for sequential studies, and intense parasitism in all organs and tissues, including the pancreas, have been detected in the acute phase. PURPOSE: To evaluate the involvement of the pancreas in acute experimental Chagas' disease in a mouse model by histopathological characterization. CASUISTIC AND METHODS: Ten BALBc mice, about 20 g, injected i.p. with 100 000 forms of the Y strain of Trypanosoma cruzi were used. The animals were sacrificed after 14 days of infection. Fragments of pancreas were processed by conventional paraffin embedding and hematoxylin-eosin staining. RESULTS: Ruptured pseudocysts and release of parasites to the extracellular medium caused by necrosis of acinar and duct cells and foci of fat were the most striking histopathological features of acute Chagasic pancreatitis. CONCLUSION: Parasitism is the main cause of acute pancreatitis in Chagas' disease.

Acute pleuropulmonary complications detected by computed tomography following myocardial revascularization

INTRODUCTION: Pleuropulmonary changes are common following coronary artery bypass grafting surgery performed with a saphenous vein graft, with or without an internal mammary artery. The presence of atelectasis or pleural effusions reflects the thoracic trauma. PURPOSE: To define the postoperative incidence of changes in the lung and in the pleural space and to evaluate the influence of the trauma. METHODS: Thirty patients underwent elective coronary artery bypass grafting surgery (8 saphenous vein grafts and 22 saphenous vein grafts and internal mammary artery grafts with pleurotomy). Chest tubes in the left pleural space were used in all internal mammary artery patients. On the second (day 2) and seventh (day 7) postoperative day, patients underwent a computed tomography, and pleural effusions were rated as follows: grade 0 = no fluid to grade 4 = fluid in more than 75% of the hemithorax. Atelectasis was rated as follows: laminar = 1, segmental = 3, and lobar = 10 points. RESULTS: All patients had pleural effusion or atelectasis. Between day 2 and day 7, the number of patients with effusions or atelectasis on the right side decreased (P < 0.05). The incidence of effusions on day 2 in the saphenous vein graft group (87.5%) was higher (P < 0.05) than in the internal mammary artery group (52.3%). The incidence of atelectasis in the lower right lobe decreased (P < 0.05) from 86.7% (day 2) to 26.7% (day 7). The degree of atelectasis in both sides did not differ on day 2 (P = 0.42) but did on day 7 (P < 0.0001). There was a decrease in the atelectasis from day 2 to day 7 on the right side (P < 0.001), but not on the left (P = 0.21). On day 2 there was a relationship between atelectasis and effusion on the right (P = 0.04), but not on the left (P = 0.113). CONCLUSION: The present series demonstrates that there is a high incidence of both minimal pleural effusion and atelectasis after coronary artery bypass grafting surgery, which drops on the right side from day 2 to day 7 post surgery. Factors that contribute to the persistence of changes on the left side include the thoracic trauma and the presence of chest tubes and pericardial effusion.

Use of tacrolimus in rescue therapy of acute and chronic rejection in liver transplantation

PURPOSE: To study the indications and results of tacrolimus as rescue therapy for acute cellular or chronic rejection in liver transplantation. PATIENTS AND METHODS: Eighteen liver transplant recipients who underwent rescue therapy with tacrolimus between March 1995 and August 1999 were retrospectively studied. The treatment indication, patients, and graft situation were recorded as of October 31st, 1999. The response to tacrolimus was defined as patient survival with a functional graft and histological reversal of acute cellular, or for chronic rejection, bilirubin serum levels decreasing to up to twice the upper normal limit. RESULTS: Fourteen cases (77.8%) presented a good response. The response rate for the different indications was: (1) acute cellular + sepsis - 0/1 case; (2) recurrent acute cellular - 1/1 case; (3) OKT3-resistant acute cellular - 2/2 cases; (4) steroid-resistant acute cellular + active viral infection - 3/3 cases; (5) chronic rejection - 8/11 cases (72.7% response rate). The 4 patients who did not respond died. CONCLUSION: Tacrolimus rescue therapy was successful in most cases of acute cellular and chronic rejection in liver transplantation.

Growth and puberty after treatment for acute lymphoblastic leukemia

Over the last 20 years, after combining treatment of chemotherapy and radiotherapy, there has been an improvement in the survival rate of acute lymphoblastic leukemia patients, with a current cure rate of around 70%. Children with the disease have been enrolled into international treatment protocols designed to improve survival and minimize the serious irreversible late effects. Our oncology unit uses the international protocol: GBTLI LLA-85 and 90, with the drugs methotrexate, cytosine, arabinoside, dexamethasone, and radiotherapy. However, these treatments can cause gonadal damage and growth impairment. PATIENTS AND METHOD: The authors analyzed 20 children off therapy in order to determine the role of the various doses of radiotherapy regarding endocrinological alterations. They were divided into 3 groups according to central nervous system prophylaxis: Group A underwent chemotherapy, group B underwent chemotherapy plus radiotherapy (18 Gy), and group C underwent chemotherapy plus radiotherapy (24 Gy). Serum concentrations of LH, FSH, GH, and testosterone were determined. Imaging studies included bone age, pelvic ultrasound and scrotum, and skull magnetic resonance imaging. RESULTS: Nine of the patients who received radiotherapy had decreased pituitary volume. There was a significant difference in the response to GH and loss of predicted final stature (Bayley-Pinneau) between the 2 irradiated groups and the group that was not irradiated, but there was no difference regarding the radiation doses used (18 or 24 Gy). The final predicted height (Bayley-Pinneau) was significantly less (P = 0.0071) in both groups treated with radiotherapy. Two girls had precocious puberty, and 1 boy with delayed puberty presented calcification of the epididymis. CONCLUSION: Radiotherapy was been responsible for late side effects, especially related to growth and puberty.

Elucidating the role of glycans in leucocyte function

RESUMO: O processo de glicosilação é a modificação pós-traducional de proteínas mais comum e está envolvido em vários processos fisiológicos e patológicos. Especificamente, certos perfis glicosídeos estão correlacionados a estados específicos de diferenciação celular, e podem modular vários eventos celulares, como sinalização celular, migração celular e interações hospedeiro-patogénio. Assim sendo, a glicosilação desempenha um papel crucial na modulação de vários processos imunológicos. No entanto, permanece por esclarecer como as estruturas glicosídicas influenciam a imunidade. Especificamente, algumas estruturas glicosídicas terminais que estão modificadas pela ligação de ácido siálico desempenham um papel importante em várias funções do sistema imune, nomeadamente migração leucocitária em contexto de inflamação e ativação de células imunes. Como tal, este trabalho teve como objectivo investigar como a expressão de certos glicanos influencia componentes importantes da resposta imune inata e adaptativa. Este trabalho está dividido em três componentes principais: 1) A imunidade está amplamente dependente da habilidade das células circulantes migrarem para os tecidos inflamados, sendo que a ligação de leucócitos à Eselectina endotelial é o primeiro passo. Assim, nós analisámos a estrutura e função dos ligandos de E-selectina que são expressos pelas células humanas mononucleares de sangue periférico (PBMCs), fornecendo novos conhecimentos para a compreensão dos intervenientes moleculares que mediam a ligação dos monócitos, células CD4+ e CD8+T e células B ao endotélio vascular. Surpreendentemente, os monócitos apresentaram maior capacidade de ligação à E-selectina comparativamente aos linfócitos. Esta observação pode ser explicada pelo facto de os monócitos humanos expressarem, uniformemente, um vasto reportório de glicoproteínas que exibem afinidade de ligação à E-selectina, nomeadamente: as glicoformas do CD43 (CD43E) e do CD44 (HCELL), em adição à já previamente reportada glicoforma da PSGL-1 (CLA). Consistentemente, a diferente capacidade que as diversas populações linfocitárias apresentam de se ligar à E-selectina, está integralmente relacionada com a sua expressão de glicoproteínas com afinidade de ligação à E-selectina. Enquanto que as células CD4+T apresentam uma elevada reatividade à E-selectina, as células CD8+T e B demonstram pouca ou nenhuma capacidade de ligação à E-selectina. Esta atividade de ligação à E-selectina das células CD4+T é conferida pela expressão de HCELL, em adição às já previamente reportadas CLA e CD43E. As células CD8+ T não expressam HCELL e apenas expressam pequenas quantidades de CLA e CD43E, enquanto que as células B não expressam ligandos de Eselectina. Mais, a exofucosilação da superfície destas células, levou ao dramático aumento da expressão dos ligandos de E-selectina em todos as populações leucocitárias, verificando-se que a criação de certos ligandos de E-selectina está dependente do tipo de célula, após fucosilação. Colectivamente, estes resultados redefinem o nosso conhecimento acerca dos mecanismos moleculares que governam o tráfico das células mononucleares de sangue periférico em contexto de inflamação. 2) A habilidade das células dendríticas (DCs) para extravasarem em locais de inflamação é crucial para o sucesso da terapia com DCs. Assim, analisámos a estrutura e função das moléculas de adesão que mediam a migração transendotelial (TEM) das DCs. Para isso, foram usadas DCs geradas a partir da diferenciação de monócitos (mo-DCS), obtidos quer pelo métodos de separação imuno-magnética de células CD14+ (CD14-S) ou por isolamento por aderência ao plástico (PA-S). Os resultados obtidos indicam que as glicoformas de ligação à Eselectina de PSGL-1, CD43 e CD44 são expressas pelas CD14-S mo-DCs, enquanto que as PA-S mo-DCs expressam apenas CLA. É importante notar que a ligação do CD44 nas mo-DCs, mas não nas PA-S mo-DCs, desencadeia a ativação e consequente adesão da VLA-4 ao endotélio na ausência de um gradiente de quimiocinas. Procedeu-se também à análise dos ligandos E-selectina expressos em mo-DCs geradas a partir de monócitos do sangue do cordão umbilical (UCB) e, inesperadamente, as UCB mo-DCs não expressam qualquer glicoproteína com reatividade à E-selectina. Além disso, a exofucosilação das mo- DCs humanas utilizando uma α(1,3)-fucosiltransferase aumenta significativamente a expressão de HCELL e, portanto, estas células apresentam uma capacidade aumentada para se ligarem à E-selectina em condições de fluxo hemodinâmico. Estes resultados destacam o papel do HCELL no desencadeamento do TEM das CD14-S mo-DCs e sugerem que estratégias para potenciar a expressão de HCELL poderão impulsionar o recrutamento de mo-DCs para locais de inflamação. 3) Outro obstáculo para alcançar o sucesso promissor de vacinas baseadas em DCs é o estabelecimento de abordagens eficientes que poderão melhorar o estado de maturação e apresentação antigénica das DCs. Por conseguinte, foram investigadas abordagens alternativas que podem superar este obstáculo. Através da remoção de ácido siálico de superfície celular das DCs, conseguiu-se induzir a maturação de DC humanas e de ratinhos. Notavelmente, tanto as DCs humanas como as de ratinho, ao serem desialiladas mostraram uma capacidade aumentada para induzir a proliferação de células T, para secretar citocinas Th1 e para induzir a morte específica de células tumorais. Em adição, as DCs desialiladas apresentam uma maior capacidade de apresentação cruzada de antigénios tumorais às células T citotóxicas. Colectivamente, o presente estudo oferece uma visão chave para optimizar a capacidade das DCs em induzir respostas imunitárias anti-tumorais, e indica que o tratamento com sialidase é uma nova tecnologia para melhorar a eficácia e aplicabilidade das vacinas baseadas em DCs. Coletivamente, os nossos resultados demostram como a glicosilação e a sua manipulação podem modular a imunidade. Concretamente, através de uma reação de exofucosilação conseguimos aumentar fortemente a capacidade de os leucócitos extravasarem para os tecidos afectados, enquanto que a remoção dos níveis de ácido siálico da superfície celular das DCs, induz potentes respostas anti-tumorais mediadas por células T citotóxicas. ------------------------------------ ABSTRACT: Glycosylation is the most widely form of protein post-translational modification and is involved in many physiological and pathological processes. Specifically, certain patterns of glycosylation are associated with determined stages of cell differentiation and can modulate processes like cell-signaling and migration and host-pathogen interactions. As such, glycosylation plays a crucial role in the modulation of several immune events. However, how glycans execute this immune-modulation and, therefore, influence immunity is still poorly unknown. Specifically, some terminal sialic acid-modified determinants are known to be involved in several physiological immune processes, including leukocyte trafficking into sites of inflammation and cell immune activation. Therefore, in this work, we sought to investigate more deeply how the expression of these glycosidic structures affects events form both innate and adaptive immune responses. To this end, we divided our work into three main parts: 1) Immunity critically depends on the ability of sentinel circulating cells to infiltrate injured sites, of which leukocyte binding to endothelial E-selectin is the critical first step. Thus, we first analyzed the structure and function of the E-selectin ligands expressed on native human peripheral blood mononuclear cells (PBMCs), providing novel insights into the molecular effectors governing adhesion of circulating monocytes, and of circulating CD4+T, CD8+T and B cells, to vascular endothelium under hemodynamic shear conditions. Strikingly, monocytes show a higher ability to tether and roll on endothelial cells than lymphocyte subsets. This is due to the fact that human circulating monocytes uniformly display a wide repertoire of E-selectin binding glycoproteins, namely the E-selectin-binding glycoforms of CD43 (CD43E) and CD44 (HCELL), in addition to the previously described E-selectin-binding glycoform of PSGL-1 (CLA). In addition, we also observed a differential ability of the different lymphocyte subsets to bind to Eselectin under hemodynamic shear stress conditions, and these differences were highly correlated with their individual expression of E-selectin binding glycoproteins. While CD4+T cells show a robust E-selectin binding ability, CD8+T and B cells show little to no E-selectin reactivity. CD4+T cell potent Eselectin rolling activity is conferred by HCELL expression, in addition to the previously reported E-selectin-binding glycoproteins CD43E and CLA. CD8+T cells display no HCELL and low amounts of CLA and CD43E, whereas B cells lack E-selectin ligand expression. Moreover, enforced exofucosylation of cell surface of these cells noticeably increases expression of functional E-selectin ligands among all leukocytes subsets, with cell type-dependent specificity in the protein scaffolds that are modified. Taken together, these findings redefine our understanding of the molecular mechanisms governing the trafficking patterns of PBMCs that are relevant in the context of acute or chronic inflammatory conditions. 2) The ability of circulating dendritic cells (DCs) to extravasate at inflammatory sites is critical to the success of DC-based therapies. Therefore, we assessed the structure and function of adhesion molecules mediating the transendothelial migration (TEM) of human monocyte derived-DCs (mo-DCs), obtained either by CD14 positive immune-magnetic selection (CD14-S) or by plastic adherence of blood monocytes (PA-S). We report for the first time that the E-selectin binding glycoforms of PSGL-1, CD43 and CD44 are all expressed on CD14-S mo-DCs, in contrast to PA-S mo-DCs that express only CLA. Importantly, CD44 engagement on CD14-S mo-DCs, but not on PA-S mo-DCs, triggers VLA-4-dependent adhesiveness and programs TEM in absence of chemokine gradient. We also analyzed the E-selectin ligands expressed on mo-DCs generated from umbilical cord blood (UCB) monocytes, and unexpectedly, UCB mo-DCs do not express any glycoprotein with E-selectin reactivity. Furthermore, exoglycosylation of human mo-DCs using an α(1,3)-fucosyltransferase significantly increases expression of HCELL, and therefore exofucosylated mo-DCs exhibit an augmented ability to bind to E-selectin under hemodynamic shear stress conditions. These findings highlight a role for HCELL engagement in priming TEM of CD14-S mo-DCs, and suggest that strategies to enforce HCELL expression could boost mo-DC recruitment to inflammatory sites. 3) Another obstacle to achieve the promising success of DC-based vaccines is the establishment of efficient approaches that could successfully enhance maturation and cross-presentation ability of DCs. Therefore, we investigated an alternative approach that can overcome this problem. Through removal of sialic acid content from DC cell surface we are able to elicit maturation of both human and mouse DCs. Notably, desialylated human and murine DCs showed enhanced ability to induce autologous T cell to proliferate, to secrete Th1 cytokines and to kill tumor cells. Moreover, desialylated DCs display enhanced cross-presentation of tumor antigens to cytotoxic CD8+ T cells. Collectively, this study offers key insight to optimize the ability of DCs to boost anti-tumor immune responses, and indicates that the treatment with an exogenous sialidase is a powerful new technology to improve the efficacy and applicability of DC-based vaccines. Overall, our findings show how glycosylation and its manipulation can modulate immunity. Concretely, through an exofucosylation reaction we are able to greatly augment the ability of leukocytes to extravasate into injured tissues, while removal of sialic acid moieties from cell surface of DCs, significantly potentiate their ability to induce anti-tumor cytotoxic T cell-mediate responses.