SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer.

The posttranslational modification of proteins critically influences many biological processes and is a key mechanism that regulates the function of the RNA-binding protein Hu antigen R (HuR), a hub in liver cancer. Here, we show that HuR is SUMOylated in the tumor sections of patients with hepatocellular carcinoma in contrast to the surrounding tissue, as well as in human cell line and mouse models of the disease. SUMOylation of HuR promotes major cancer hallmarks, namely proliferation and invasion, whereas the absence of HuR SUMOylation results in a senescent phenotype with dysfunctional mitochondria and endoplasmic reticulum. Mechanistically, SUMOylation induces a structural rearrangement of the RNA recognition motifs that modulates HuR binding affinity to its target RNAs, further modifying the transcriptomic profile toward hepatic tumor progression. Overall, SUMOylation constitutes a mechanism of HuR regulation that could be potentially exploited as a therapeutic strategy for liver cancer.

Factor-inhibiting HIF (FIH) promotes lung cancer progression.

Factor-inhibiting HIF (FIH) is an asparagine hydroxylase that acts on hypoxia-inducible factors (HIFs) to control cellular adaptation to hypoxia. FIH is expressed in several tumor types, but its impact in tumor progression remains largely unexplored. We observed that FIH was expressed on human lung cancer tissue. Deletion of FIH in mouse and human lung cancer cells resulted in an increased glycolytic metabolism, consistent with increased HIF activity. FIH-deficient lung cancer cells exhibited decreased proliferation. Analysis of RNA-Seq data confirmed changes in the cell cycle and survival and revealed molecular pathways that were dysregulated in the absence of FIH, including the upregulation of angiomotin (Amot), a key component of the Hippo tumor suppressor pathway. We show that FIH-deficient tumors were characterized by higher immune infiltration of NK and T cells compared with FIH competent tumor cells. In vivo studies demonstrate that FIH deletion resulted in reduced tumor growth and metastatic capacity. Moreover, high FIH expression correlated with poor overall survival in non-small cell lung cancer (NSCLC). Our data unravel FIH as a therapeutic target for the treatment of lung cancer.

Abordagem à pessoa nos Serviço de Urgência e Unidade de Cuidados Intensivos após a pandemia COVID-19: scoping review / Approach to the person in emergency and intensive care after the pandemic covid-19: scoping review

Objetivo: Perceber quais as alterações que ocorreram na abordagem à pessoa em situação crítica no Serviço de Urgência e Unidade de Cuidados Intensivos após início da pandemia COVID-19. Método: A estratégia de pesquisa para a scopingreview foi realizada nas bases de dados Medline via PubMed, EBSCO Host, BioMed Central, ScienceDirect, BVS e Scielo através da utilização de descritores MeSH e DeCS, artigos com fulltext gratuito, publicados em língua portuguesa, inglesa e espanhola, com datas de publicação entre 2019 e 2021, implementados critérios de inclusão e exclusão.Resultados: Foram identificados 4 estudos elegíveis para análise, publicados em 2020, nenhum dos estudos em Português. Conclusão: As principais alterações estão relacionadas com a utilização de equipamento de proteção individual, colocando o enfoque na segurança dos profissionais de saúde.(AU)

Aim: To understand the changes that occurred in the approach to critically ill patients in the Emergency Department and Intensive Care Unit after the beginning of the COVID-19 pandemic. Method: The search strategy for the scoping review was conducted in Medline databases via PubMed, EBSCO Host, BioMed Central, ScienceDirect, BVS and Scielo by using MeSH and DeCS descriptors, articles with free full text, published in Portuguese, English and Spanish language, with publication dates between 2019 and 2021, implemented inclusion and exclusion criteria.Results: Four eligible studies were identified for analysis, published in 2020, and none of the studies was in Portuguese. Conclusion: The main changes are related to the use of personal protective equipment, focusing on the safety of health professionals.(AU)

Objetivo: Conocer qué cambios se han producido en el abordaje a los pacientes críticos en el Servicio de Urgencia y enUnidades de Cuidados Intensivos tras el inicio de la pandemia COVID-19.Método: La estrategia de búsqueda para la revisión se realizó en las bases de datos Medline e PubMed, EBSCO Host, BioMed Central, ScienceDirect, BVS y Scielo con el uso de descriptores MeSH y DeCS, artículos con libre acceso a texto completo, publicados en portugués, inglés y español, entre el 2019 y 2021, usando criterios de inclusión y exclusión.Resultados: Identificamos 4 estudios elegibles para el análisis, todos publicados en 2020, e ninguno en portugués.Conclusión: Los principales cambios están relacionados con el uso de equipamientos de protección personal, conel enfoque en la seguridad de los profesionales de salud.(AU)

A challenging case of granulomatosis with polyangiitis with cardiac involvement: a rare case report.

Background: Granulomatosis with polyangiitis (GPA), a systemic antineutrophil cytoplasmic antibody (ANCA) associated vasculitis, is characterized by inflammation of the small arteries, arterioles, and capillaries classically manifesting with glomerulonephritis and necrotizing granulomatous lesions of the upper and lower respiratory tract. With an incidence of approximately 12 cases per one million individuals per year it is an uncommon diagnosis that typically presents as frequent pulmonary and sinus infections; however, if left without definitive treatment progresses to more severe manifestations specifically hemoptysis and hematuria. Case Description: This case report highlights a 15-year-old woman who had both classic and non-classic findings making the diagnosis challenging. Specifically, her age of presentation, improvement with anti-microbials, and coronary dilation were not classic. Additionally, her lab work was negative for the cytoplasmic subset antineutrophil cytoplasmic autoantibody (c-ANCA), but positive for serum anti-proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) which further delayed the ultimate diagnosis as this is typically c-ANCA positive. Conclusions: Other systemic vasculitides, such as mucocutaneous lymph node disease, are associated with cardiac pathology necessitating further medical management and follow-up to prevent increased morbidity and mortality. Knowing this, we conclude that further evaluation for cardiac pathology would be prudent as part of the initial workup of patients with a diagnosis of GPA. Included is a brief review of available literature on GPA to emphasize the typical presentation, lab findings, and importance of early diagnosis.

Pseudomonas aeruginosa Bloodstream Infection, Resistance, and Mortality: Do Solid Organ Transplant Recipients Do Better or Worse?

BACKGROUND: The prevalence of antimicrobial resistance of Pseudomonas aeruginosa (P. aeruginosa) in solid organ transplant (SOT) recipients is higher than that of the general population. However, the literature supporting this statement is scarce. Identifying patients at risk of carbapenem resistance (CR) is of great importance, as CR strains more often receive inappropriate empiric antibiotic therapy, which is independently associated with mortality in bloodstream infections (BSIs). METHODS: We prospectively recorded data from all consecutive BSIs from January 1991 to July 2019 using a routine purpose-designed surveillance database. The following variables were included: age, sex, type of transplant, use of vascular and urinary catheters, presence of neutropenia, period of diagnosis, treatment with steroids, origin of BSI, source of bacteremia, septic shock, ICU admission, mechanical ventilation, previous antibiotic treatment, treatment of bacteremia, and 30-day all-cause mortality. RESULTS: We identified 2057 episodes of P. aeruginosa BSI. Of these, 265 (13%) episodes corresponded to SOT recipients (130 kidney transplants, 105 liver, 9 hearts, and 21 kidney-pancreas). Hematologic malignancy [OR 2.71 (95% CI 1.33-5.51), p = 0.006] and prior carbapenem therapy [OR 2.37 (95% CI 1.46-3.86), p < 0.001] were associated with a higher risk of having a CR P. aeruginosa BSI. Age [OR 1.03 (95% CI 1.02-1.04) p < 0.001], urinary catheter [OR 2.05 (95% CI 0.37-3.06), p < 0.001], shock at onset [OR 6.57 (95% CI 4.54-9.51) p < 0.001], high-risk source [OR 4.96 (95% CI 3.32-7.43) p < 0.001], and bacteremia caused by CR strains [OR 1.53 (95% CI 1.01-2.29) p = 0.036] were associated with increased mortality. Correct empirical therapy was protective [OR 0.52 (95% CI 0.35-0.75) p = 0.001]. Mortality at 30 days was higher in non-SOT patients (21% vs. 13%, p = 0.002). SOT was not associated with a higher risk of having a CR P. aeruginosa BSI or higher mortality. CONCLUSIONS: In our cohort of 2057 patients with P. aeruginosa BSIs, hematologic malignancies and previous carbapenem therapy were independently associated with a risk of presenting CR P. aeruginosa BSI. Age, urinary catheter, high-risk source, bacteremia caused by carbapenem-resistant strains, and severity of the infection were independently associated with mortality, whereas correct empirical therapy was a protective factor. An increasing trend in the resistance of P. aeruginosa was found, with >30% of the isolates being resistant to carbapenems in the last period. SOT was not associated with a higher risk of carbapenem-resistant BSIs or higher mortality.

Intestinal pneumatosis as a manifestation of systemic sclerosis.

A 60-year-old female patient was admitted to the emergency room for a 7-day history of abdominal bloating, nausea, vomiting, constipation, and lack of flatus. She had been diagnosed with systemic sclerosis (SSc) 10 years ago and had been using methotrexate, sildenafil, and prednisone. She did not present any signs of instability, but physical examination showed malnourishment status and abdominal tenderness and distention. Plain abdominal radiography was suggestive of sigmoid volvulus, confirmed and successfully resolved after endoscopic decompression therapy. Eight months later, the patient developed a new episode of abdominal obstruction. Computed Tomography (CT) scan identified a distended sigmoid colon due to its torsion with gas areas within the bowel wall. This time, endoscopic decompression had failed to treat, so exploratory laparotomy was performed. Colonic distention and sigmoid volvulus were identified during the procedure, after which sigmoidectomy followed by primary anastomosis was performed. Neither perforation nor masses were found. Furthermore, the anatomopathological study was inconsistent with vascular, inflammatory, or neoplastic diseases.

Impaired repair properties of endothelial colony-forming cells in patients with granulomatosis with polyangiitis.

In patients with ANCA-associated vasculitis, interactions between neutrophils and endothelial cells cause endothelial damage and imbalance. Endothelial colony-forming cells (ECFCs) represent a cellular population of the endothelial lineage with proliferative capacity and vasoreparative properties. This study aimed to evaluate the angiogenic capacity of ECFCs of patients with granulomatosis with polyangiitis (GPA). The ECFCs of 13 patients with PR3-positive GPA and 14 healthy controls were isolated and characterized using fluorescence-activated cell sorting, capillary tube formation measurement, scratching assays and migration assays with and without plasma stimulation. Furthermore, three patients with active disease underwent post-treatment recollection of ECFCs for longitudinal evaluation. The ECFCs from the patients and controls showed similar capillary structure formation. However, the ECFCs from the patients with inactive GPA exhibited early losses of angiogenic capacity. Impairments in the migration capacities of the ECFCs were also observed in patients with GPA and controls (12th h, p = 0.05). Incubation of ECFCs from patients with GPA in remission with plasma from healthy controls significantly decreased migration capacity (p = 0.0001). Longitudinal analysis revealed that treatment significantly lowered ECFC migration rates. This study revealed that ECFCs from the patients with PR3-positive GPA in remission demonstrated early losses of tube formation and reduced migration capacity compared to those of the healthy controls, suggesting impairment of endothelial function.

Hypoxia reduces cell attachment of SARS-CoV-2 spike protein by modulating the expression of ACE2, neuropilin-1, syndecan-1 and cellular heparan sulfate.

A main clinical parameter of COVID-19 pathophysiology is hypoxia. Here we show that hypoxia decreases the attachment of the receptor-binding domain (RBD) and the S1 subunit (S1) of the spike protein of SARS-CoV-2 to epithelial cells. In Vero E6 cells, hypoxia reduces the protein levels of ACE2 and neuropilin-1 (NRP1), which might in part explain the observed reduction of the infection rate. In addition, hypoxia inhibits the binding of the spike to NCI-H460 human lung epithelial cells by decreasing the cell surface levels of heparan sulfate (HS), a known attachment receptor of SARS-CoV-2. This interaction is also reduced by lactoferrin, a glycoprotein that blocks HS moieties on the cell surface. The expression of syndecan-1, an HS-containing proteoglycan expressed in lung, is inhibited by hypoxia on a HIF-1α-dependent manner. Hypoxia or deletion of syndecan-1 results in reduced binding of the RBD to host cells. Our study indicates that hypoxia acts to prevent SARS-CoV-2 infection, suggesting that the hypoxia signalling pathway might offer therapeutic opportunities for the treatment of COVID-19.

Hypoxia Promotes Syndecan-3 Expression in the Tumor Microenvironment.

The syndecan (Sdc) family is comprised of four members of cell surface molecules (Sdc-1 to 4) with different biological functions. Syndecan-3 (Sdc-3) is known to be mainly expressed in the brain and nervous tissue and plays a key role in development, cell adhesion, and migration. Recent studies point to important roles for Sdc-3 in inflammatory disease, but the patterns of expression and significance of Sdc-3 in cancer remains unexplored. Here we show that Sdc-3 expression is upregulated on several cancer types, especially in solid tumors that are known to be hypoxic. The Cancer Genome Atlas program (TCGA) data demonstrated that Sdc-3 expression in the tumor microenvironment positively correlates with a hypoxia gene signature. To confirm a potential cause-effect, we performed experiments with tumor cell lines showing increased expression upon in vitro exposure to 1% oxygen or dimethyloxalylglycine, an inhibitor of prolyl hydroxylases, indicating that Sdc-3 expression is promoted by hypoxia inducible factors (HIFs). HIF-1α was responsible for this upregulation as confirmed by CRISPR-engineered tumor cells. Using single-cell RNA sequencing data of melanoma patients, we show that Sdc-3 is expressed on tumor associated macrophages, cancer cells, and endothelial cells. Syndecan-3 expression positively correlated with a macrophage gene signature across several TCGA cancer types. In vitro experiments demonstrated that hypoxia (1% oxygen) or treatment with IFN-γ stimulate Sdc-3 expression on RAW-264.7 derived macrophages, linking Sdc-3 expression to a proinflammatory response. Syndecan-3 expression correlates with a better patient overall survival in hypoxic melanoma tumors.

The Mitochondrial Isoform of FASTK Modulates Nonopsonic Phagocytosis of Bacteria by Macrophages via Regulation of Respiratory Complex I.

Phagocytosis is a pivotal process by which innate immune cells eliminate bacteria. In this study, we explore novel regulatory mechanisms of phagocytosis driven by the mitochondria. Fas-activated serine/threonine kinase (FASTK) is an RNA-binding protein with two isoforms, one localized to the mitochondria (mitoFASTK) and the other isoform to cytosol and nucleus. The mitoFASTK isoform has been reported to be necessary for the biogenesis of the mitochondrial ND6 mRNA, which encodes an essential subunit of mitochondrial respiratory complex I (CI, NADH:ubiquinone oxidoreductase). This study investigates the role and the mechanisms of action of FASTK in phagocytosis. Macrophages from FASTK─/─ mice exhibited a marked increase in nonopsonic phagocytosis of bacteria. As expected, CI activity was specifically reduced by almost 50% in those cells. To explore if decreased CI activity could underlie the phagocytic phenotype, we tested the effect of CI inhibition on phagocytosis. Indeed, treatment with CI inhibitor rotenone or short hairpin RNAs against two CI subunits (NDUFS3 and NDUFS4) resulted in a marked increase in nonopsonic phagocytosis of bacteria. Importantly, re-expression of mitoFASTK in FASTK-depleted macrophages was sufficient to rescue the phagocytic phenotype. In addition, we also report that the decrease in CI activity in FASTK─/─ macrophages is associated with an increase in phosphorylation of the energy sensor AMP-activated protein kinase (AMPK) and that its inhibition using Compound C reverted the phagocytosis phenotype. Taken together, our results clearly demonstrate for the first time, to our knowledge, that mitoFASTK plays a negative regulatory role on nonopsonic phagocytosis of bacteria in macrophages through its action on CI activity.

Arrabidaea chica for oral mucositis in patients with head and neck cancer: a protocol of a randomised clinical trial.

INTRODUCTION: Oral mucositis is an iatrogenic condition of erythematous inflammatory changes which tends to occur on buccal and labial surfaces, the ventral surface of the tongue, the floor of the mouth and the soft palate of patients receiving chemotherapy. This protocol of ongoing randomised parallel group clinical trial aims to access the therapeutic effect of an herbal gel containing 2.5% Arrabidaea chica Verlot standardised extract on oral mucositis in patients with head and neck cancer compared with low-level laser therapy. METHODS AND ANALYSIS: Patients with head and neck cancer held at Clinics Hospital of University of Campinas, Sao Paulo, who develop early signs/symptoms of oral mucositis are eligible. Baseline characteristics of participants include oral mucositis grade and quality of life assessments. Enrolment started in November 2017 with allocation of patients to one of the study groups by means of randomisation. Patients will be treated either with Arrabidaea chica or laser until wound healing. Monitoring includes daily assessment of mucositis grade and diameter measurement by photographs and millimetre periodontal probe. Treatments will be concluded once mucositis is healed. A blinded assessor will evaluate mucositis cure after referred by the study team. At this point, the gel tube will be weighed to indirectly assess patient's compliance. At close-out, data will be analysed by a blinded researcher following the procedures described in the statistical analyses. ETHICS AND DISSEMINATION: This clinical trial was approved by the ethics committee of research in humans at the Faculty of Medical Sciences of University of Campinas (report no. 1,613,563/2016). Results from this trial will be communicated in peer-reviewed publications and scientific presentations. TRIAL REGISTRATION NUMBER: RBR-5×4397.

IL-1ß inflammatory response driven by primary breast cancer prevents metastasis-initiating cell colonization.

Lack of insight into mechanisms governing breast cancer metastasis has precluded the development of curative therapies. Metastasis-initiating cancer cells (MICs) are uniquely equipped to establish metastases, causing recurrence and therapeutic resistance. Using various metastasis models, we discovered that certain primary tumours elicit a systemic inflammatory response involving interleukin-1ß (IL-1ß)-expressing innate immune cells that infiltrate distant MIC microenvironments. At the metastatic site, IL-1ß maintains MICs in a ZEB1-positive differentiation state, preventing MICs from generating highly proliferative E-cadherin-positive progeny. Thus, when the inherent plasticity of MICs is impeded, overt metastases cannot be established. Ablation of the pro-inflammatory response or inhibition of the IL-1 receptor relieves the differentiation block and results in metastatic colonization. Among patients with lymph node-positive breast cancer, high primary tumour IL-1ß expression is associated with better overall survival and distant metastasis-free survival. Our data reveal complex interactions that occur between primary tumours and disseminated MICs that could be exploited to improve patient survival.

Short-Term Peripheral Venous Catheter-Related Bloodstream Infections: Evidence for Increasing Prevalence of Gram-Negative Microorganisms from a 25-Year Prospective Observational Study.

The aim of this study was to describe the etiology and outcome of short-term peripheral venous catheter (PVC)-related bloodstream infections (PVCRBSI) in a 25-year period (1992 to 2016) and to identify predictive factors of Gram-negative PVCRBSI. This was a prospective observational study including all episodes of PVCRBSI. A multivariate logistic regression model adjusted for calendar year was built to explore factors associated with a Gram-negative bacterial etiology. Over the study period, 711 episodes of PVCRBSI were identified. Incidence rate of PVCRBSI increased from 0.06 to 0.13 episodes/1,000 patient-days. A Gram-negative bacterial etiology was demonstrated in 162 (22.8%) episodes. There was a significant increase in the proportion of Gram-negative infections (22.6% in 1992 to 1996 versus 33.2% in 2012 to 2016). Independent predictive factors of Gram-negative PVCRBSI were the following: being in the hospital for more than 7 days with a catheter in situ for more than 3 days (adjusted odds ratio [aOR], 1.80; 95% confidence interval [CI], 1.20 to 2.69), surgery in the previous month (aOR, 2.39; 95% CI, 1.40 to 4.09), and antimicrobial treatment with beta-lactams (aOR, 1.80; 95% CI, 1.16 to 2.78). In conclusion, we reported an increase in the prevalence of Gram-negative PVCRBSI over the last 25 years. Factors associated with a Gram-negative bacterial etiology were being in the hospital for more than 7 days with a catheter in situ for more than 3 days, having undergone surgery, and having received antimicrobial treatment with beta-lactams.

Foreign Body in Jugal Mucosa

Introduction Foreign body in the oral cavity may be asymptomatic for long time and only sometimes it can lead to a typical granulomatous foreign body reaction. Some patients may complain of oral pain and present signs of inflammation with purulent discharge. A granuloma is a distinct, compact microscopic structure composed of epithelioid-shaped macrophages typically surrounded by a rim of lymphocytes and filled with fibroblasts and collagen. Nowadays, the increase of cosmetic invasive procedures such as injection of prosthetic materials in lips and cheeks may lead to unusual forms of inflammatory granulomas. Objectives Describe an unusual presentation of a foreign body reaction in the buccal mucosa due to previous injection of cosmetic agent. Resumed Report A 74-year-old woman was referred to the Department of Otorhinolaryngology, Head and Neck Surgery to investigate the presence of multiple painless, bilateral nodules in the buccal mucosa, with progressive growth observed during the previous 2months. The histologic results showed a foreign body inflammatory reaction. Conclusion Oral granulomatosis lesions represent a challenging diagnosis for clinicians and a biopsy may be necessary. Patients may feel ashamed to report previous aesthetic procedures, and the clinicians must have a proactive approach.(AU)

Foreign Body in Jugal Mucosa.

Introduction Foreign body in the oral cavity may be asymptomatic for long time and only sometimes it can lead to a typical granulomatous foreign body reaction. Some patients may complain of oral pain and present signs of inflammation with purulent discharge. A granuloma is a distinct, compact microscopic structure composed of epithelioid-shaped macrophages typically surrounded by a rim of lymphocytes and filled with fibroblasts and collagen. Nowadays, the increase of cosmetic invasive procedures such as injection of prosthetic materials in lips and cheeks may lead to unusual forms of inflammatory granulomas. Objectives Describe an unusual presentation of a foreign body reaction in the buccal mucosa due to previous injection of cosmetic agent. Resumed Report A 74-year-old woman was referred to the Department of Otorhinolaryngology, Head and Neck Surgery to investigate the presence of multiple painless, bilateral nodules in the buccal mucosa, with progressive growth observed during the previous 2 months. The histologic results showed a foreign body inflammatory reaction. Conclusion Oral granulomatosis lesions represent a challenging diagnosis for clinicians and a biopsy may be necessary. Patients may feel ashamed to report previous aesthetic procedures, and the clinicians must have a proactive approach.

[Liponeurocytoma in the left lateral ventricle. Presentation of the first case reported in Spain and literature review]. / Liponeurocitoma del ventrículo lateral izquierdo. Revisión del primer caso descrito en España y análisis de la bibliografía.

Supratentorial liponeurocytoma is a rare tumor, predominantly appearing in young males. It most commonly affects the lateral ventricles, with involvement of the third ventricle being exceptional. It is defined as a low-grade neuroglial tumor, with areas of associated lipomatosis. The most common clinical manifestation is that resulting from the presence of secondary intracranial hypertension and hydrocephalus. We present the first case reported in Spain of this tumor type and one of the few appearing in the literature so far. We report the case of a 33-year-old male patient, suffering from crural sensitive symptoms and recent onset headache. The radiographic study revealed the presence of a large supratentorial tumor; intraventricular, multicystic, heterogeneous and with areas of associated lipomatosis. The patient underwent surgery and complete tumor resection was achieved. The definitive diagnosis was of supratentorial liponeurocytoma. The presence of a supratentorial intraventricular tumor with areas of fatty degeneration should lead us to consider this type of tumor in the differential diagnosis. Complete tumor resection is considered to be the treatment of choice.

HACEK infective endocarditis: characteristics and outcomes from a large, multi-national cohort.

The HACEK organisms (Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) are rare causes of infective endocarditis (IE). The objective of this study is to describe the clinical characteristics and outcomes of patients with HACEK endocarditis (HE) in a large multi-national cohort. Patients hospitalized with definite or possible infective endocarditis by the International Collaboration on Endocarditis Prospective Cohort Study in 64 hospitals from 28 countries were included and characteristics of HE patients compared with IE due to other pathogens. Of 5591 patients enrolled, 77 (1.4%) had HE. HE was associated with a younger age (47 vs. 61 years; p<0.001), a higher prevalence of immunologic/vascular manifestations (32% vs. 20%; p<0.008) and stroke (25% vs. 17% p = 0.05) but a lower prevalence of congestive heart failure (15% vs. 30%; p = 0.004), death in-hospital (4% vs. 18%; p = 0.001) or after 1 year follow-up (6% vs. 20%; p = 0.01) than IE due to other pathogens (n = 5514). On multivariable analysis, stroke was associated with mitral valve vegetations (OR 3.60; CI 1.34-9.65; p<0.01) and younger age (OR 0.62; CI 0.49-0.90; p<0.01). The overall outcome of HE was excellent with the in-hospital mortality (4%) significantly better than for non-HE (18%; p<0.001). Prosthetic valve endocarditis was more common in HE (35%) than non-HE (24%). The outcome of prosthetic valve and native valve HE was excellent whether treated medically or with surgery. Current treatment is very successful for the management of both native valve prosthetic valve HE but further studies are needed to determine why HE has a predilection for younger people and to cause stroke. The small number of patients and observational design limit inferences on treatment strategies. Self selection of study sites limits epidemiological inferences.

Atuação multidisciplinar em faringoestomatologia / Multidisciplinary approach in stomatology

Objetivo: Este artigo tem o objetivo de analisar dadosepidemiológicos e clínicos do serviço de faringoestomatologia dadisciplina de otorrinolaringologia, cabeça e pescoço de todos ospacientes atendidos nos primeiros dez meses de funcionamento.Método: Foram atendidos 41 pacientes, a idade média dospacientes atendidos foi de 52 anos (12-80). Resultados: O tempomédio de duração das queixas principais foi de 38 meses. A queixamais frequente foi lesão na cavidade oral, seguida de xerostomiae ardência bucal. Dez (24%) dos 41 pacientes eram tabagistase seis (14%) ex-tabagistas. As patologias mais frequentes foramcandidíase, refluxo faringolaríngeo, má adaptação da prótesedentária, leucoplasias e síndrome da ardência bucal. A presençade serviços de faringoestomatogia em hospitais terciários éessencial para a avaliação, seguimento e tratamento adequado depacientes com patologias específicas da área. Conclusão: Houvediversidade e riqueza de situações clínicas em nosso serviço.Alguns hábitos como o tabagismo, uso e manutenção inadequadosde prótese dentária foram bastante frequentes. A abordagemmultidisciplinar na avaliação e tratamento dos pacientes faz partedo serviço contribuindo para uma melhor formação do residente.

Survival, causes of death, and prognostic factors in systemic sclerosis: analysis of 947 Brazilian patients.

OBJECTIVE: To analyze survival, prognostic factors, and causes of death in a large cohort of patients with systemic sclerosis (SSc). METHODS: From 1991 to 2010, 947 patients with SSc were treated at 2 referral university centers in Brazil. Causes of death were considered SSc-related and non-SSc-related. Multiple logistic regression analysis was used to identify prognostic factors. Survival at 5 and 10 years was estimated using the Kaplan-Meier method. RESULTS: One hundred sixty-eight patients died during the followup. Among the 110 deaths considered related to SSc, there was predominance of lung (48.1%) and heart (24.5%) involvement. Most of the 58 deaths not related to SSc were caused by infection, cardiovascular or cerebrovascular disease, and cancer. Male sex, modified Rodnan skin score (mRSS) > 20, osteoarticular involvement, lung involvement, and renal crisis were the main prognostic factors associated to death. Overall survival rate was 90% for 5 years and 84% for 10 years. Patients presented worse prognosis if they had diffuse SSc (85% vs 92% at 5 yrs, respectively, and 77% vs 87% at 10 yrs, compared to limited SSc), male sex (77% vs 90% at 5 yrs and 64% vs 86% at 10 yrs, compared to female sex), and mRSS > 20 (83% vs 90% at 5 yrs and 66% vs 86% at 10 yrs, compared to mRSS < 20). CONCLUSION: Survival was worse in male patients with diffuse SSc, and lung and heart involvement represented the main causes of death in this South American series of patients with SSc.