Effects of chlorhexidine gluconate oral care on hospital mortality : a hospital-wide, observational cohort study

Chlorhexidine oral care is widely used in critically and non-critically ill hospitalized patients to maintain oral health. We investigated the effect of chlorhexidine oral care on mortality in a general hospitalized population. In this single-center, retrospective, hospital-wide, observational cohort study we included adult hospitalized patients (2012-2014). Mortality associated with chlorhexidine oral care was assessed by logistic regression analysis. A threshold cumulative dose of 300 mg served as a dichotomic proxy for chlorhexidine exposure. We adjusted for demographics, diagnostic category, and risk of mortality expressed in four categories (minor, moderate, major, and extreme). The study cohort included 82,274 patients of which 11,133 (14%) received chlorhexidine oral care. Low-level exposure to chlorhexidine oral care (ae 300 mg) was associated with increased risk of death [odds ratio (OR) 2.61; 95% confidence interval (CI) 2.32-2.92]. This association was stronger among patients with a lower risk of death: OR 5.50 (95% CI 4.51-6.71) with minor/moderate risk, OR 2.33 (95% CI 1.96-2.78) with a major risk, and a not significant OR 1.13 (95% CI 0.90-1.41) with an extreme risk of mortality. Similar observations were made for high-level exposure (> 300 mg). No harmful effect was observed in ventilated and non-ventilated ICU patients. Increased risk of death was observed in patients who did not receive mechanical ventilation and were not admitted to ICUs. The adjusted number of patients needed to be exposed to result in one additional fatality case was 47.1 (95% CI 45.2-49.1). These data argue against the indiscriminate widespread use of chlorhexidine oral care in hospitalized patients, in the absence of proven benefit in specific populations

Angiotensinogen: Hormonal regulation and relative importance in the generation of angiotensin II

Angiotensinogen: Hormonal regulation and relative importance in the generation of angiotensin II. The production of angiotensinogen is controlled mainly by hormones that affect the concentration of its mRNA in tissues. Accordingly, hormones that act upon gene transcription play a prominent role. However, other factors may modulate the transcriptional effects of hormones, and these should be considered to appreciate the final effects of hormones on the secretion of angiotensinogen. The most important role played by hormones in the regulation of angiotensinogen may be to maintain its production in the face of rapid consumption by high levels of renin. However, elevated levels of angiotensinogen may become a risk factor in situations where the normal feedback regulation of renin does not operate normally. Finally, the synthesis of angiotensinogen in tissues may be regulated differentially than that in liver, although the exact importance of these observations is still poorly understood

Studies of the role of sialyl Lewis X antigen and E selectin ligands in colorectal cancer

Glycosylation alterations dysregulate multiple biological processes and are a hallmark of cancer, linked to tumorigenesis and tumour progression. The present study focuses on altered glycosylation in colorectal cancer (CRC), the third most common cancer worldwide. Increased sialylation and fucosylation are reported in CRC and associated with malignant tumour features. This increase is translated by upregulation of the sialofucosylated sialyl Lewis X (sLeX) antigen, a ligand of the endothelial E-selectin, having a potential role in metastasis. Thus, overexpressing sLeX antigen may affect the expression of E-selectin ligands and the invasion capacity of CRC cell lines. Moreover, the effect of increased sLeX antigen expression on tumour cells immunosuppressive strategies has not been clearly examined so far. To address these hypotheses, we first characterised the impact on the biology and the glycan profile of sLeX overexpression in CRC cells. The results showed improvement of cell migration and reactivity with E-selectin, upon increased sLeX expression. Then, we identified the glycoproteins immunoprecipitated with E-selectin by mass spectrometry, and our results revealed neural cell adhesion molecule L1 (L1CAM). Furthermore, we showed that the sLeX antigen overexpression by CRC cells reduces the maturation profile of dendritic cells (DCs), as inferred by a decreased expression of the antigen presenting molecule, MHC-II, and the co-stimulatory molecule, CD86. This thesis is the first to report the L1CAM ability to interact with E-selectin. Since L1CAM is known to be elevated in cancer and associated with metastasis and progression, this should contribute to better understand its action mechanism. Also, the reduced DCs maturation induced by sLeX expressing CRC cells, may diminished the capacity to appropriately engage immune response against tumour cells. Overall, these findings contribute to elucidate the role of sLeX antigen and E-selectin ligands on CRC progression, metastasis and in the tumour immune system escape strategy, proposing potential novel targets for therapeutic treatments of CRC.As alterações da glicosilação desregulam múltiplos processos biológicos e são características do cancro, relacionadas com a tumorigénese e progressão tumoral. Este estudo foca-se na glicosilação alterada em cancro colorretal (CRC), o terceiro cancro mais comum no mundo. Um aumento da sialilação e fucosilação foram reportados em CRC e associados com características de tumores malignos. Estas alterações resultaram num incremento da expressão do antigénio sialofucosilado sialil Lewis X (sLeX), um ligando da E-selectina endotelial, tendo potencial na formação de metástases. Assim, a sobreexpressão do antigénio sLeX pode afectar a expressão dos ligandos da E-selectina e a capacidade de invasão de linhas celulares de CRC. Além disso, o efeito da expressão aumentada do antigénio sLeX em estratégias imunossupressoras de células tumorais não foram claramente discutidas até à data. Para responder a estas hipóteses, primeiro caracterizámos o impacto na biologia e no perfil de glicanos da sobreexpressão de sLeX em células de CRC. Os resultados mostraram melhoria na migração celular e na reatividade com a E-selectina quando a expressão de sLeX foi aumentada. Em seguida, identificámos as glicoproteínas imunoprecipitadas com E-selectina por espectrometria de massa, e os nossos resultados revelaram a molécula de adesão das células neurais L1 (L1CAM). Para além disso, mostrámos que a sobreexpressão do antigénio sLeX nas células de CRC reduz o perfil de maturação das células dendríticas (DCs), conforme indicado pela diminuição na expressão da molécula de apresentação de antigénios, MHC-II, e a molécula co-estimuladora, CD86. Esta tese é a primeira a relatar a capacidade de interação da L1CAM com a E-selectina. Como é conhecido que a L1CAM possui uma elevada expressão em cancro e que está associada com metástases e progressão tumoral, estes resultados devem contribuir para melhor compreender o seu mecanismo de ação. Também a redução na maturação das DCs induzida por células de CRC que expressam sLeX pode diminuir a capacidade de iniciar adequadamente a resposta imunológica contra células tumorais. Em geral, estes resultados contribuem para elucidar o papel do antigénio sLeX e dos ligandos de E-selectina na progressão do CRC, na formação de metástases e na estratégia tumoral de evasão do sistema imunológico, propondo novos potenciais alvos para tratamentos terapêuticos para o CRC

The Physical projector and topological quantum field theories: U(1) Chern-Simons theory in (2+1)-dimensions

The recently proposed physical projector approach to the quantisation of gauge invariant systems is applied to the U(1) Chern-Simons theory in 2+1 dimensions as one of the simplest examples of a topological quantum field theory. The physical projector is explicitely demonstrated to be capable of effecting the required projection from the initially infinite number of degrees of freedom to the finite set of gauge invariant physical states whose properties are determined by the topology of the underlying manifold. Comment: 24 pages, no figures, plain LaTeX file; one more reference added. Final version to appear in Jour. Phys.

The effect of smoking on survival and bone loss of implants with a fluoride-modified surface: a 2-year retrospective analysis of 1106 implants placed in daily practice

Aim: To compare survival and peri-implant bone loss of implants with a fluoride-modified surface in smokers and nonsmokers. Materials and Methods: Patient files of all patients referred for implant treatment from November 2004 to 2007 were scrutinized. All implants were placed by the same experienced surgeon (BC). The only inclusion criterion was a follow-up time of at least 2 years. Implant survival and bone loss were assessed by an external calibrated examiner (SV) comparing digital peri-apical radiographs taken during recall visits with the post-operative ones. Implant success was determined according to the international success criteria (Albrektsson et al. 1986). Survival of implants installed in smokers and nonsmokers were compared using the log-rank test. Both non-parametric tests and fixed model analysis were adopted to evaluate bone loss in smokers and nonsmokers. Results: 1106 implants in 300 patients (186 females; 114 males) with a mean follow-up of 31 months (SD 7.15; range 24-58) were included. 19 implants in 17 patients failed, resulting in an overall survival rate of 98.3% on implant level and 94.6% on patient level. After a follow-up period of 2 years, the CSR was 96.7% and 99.1% with the patient and implant as statistical unit respectively. Implant survival was significantly higher for nonsmokers compared to smokers (implant level p = 0.025; patient level p = 0.017). The overall mean bone loss was 0.34 mm (n = 1076; SD 0.65; range 0.00-7.10). Smokers lost significantly more bone compared to nonsmokers in the maxilla (0.74 mm; SD 1.07 vs 0.33 mm; SD 0.65; p < 0.001), but not in the mandible (0.25mm; SD 0.65 vs 0.22mm; SD 0.50; p = 0.298). Conclusion: The present study is the first to compare peri-implant bone loss in smokers and nonsmokers from the time of implant insertion (baseline) to at least 2 years of follow-up. Implants with a fluoride-modified surface demonstrated a high survival rate and limited bone loss. However, smokers are at higher risk to experience implant failure and more prone to show peri-implant bone loss in the maxilla. Whether this bone loss is predicting future biological complications remains to be evaluated

The impact of an interventional counselling procedure in families with a BRCA1/2 gene mutation : efficacy and safety

Background: Predictive genetic testing has high impact on cancer prevention for BRCA carriers and passing this information in BRCA families is important. Mostly, this is proband-mediated but this path is defective and denies relatives lifesaving information. Objective: To assess the efficacy/safety of an intervention, in which relatives are actively informed. Design: Sequential prospective study in new BRCA families. The proband informed relatives about predictive testing (phase I). After 6 months, a letter was sent to adult relatives who had not been reached (phase II). Then a phone call was made to obtain a final notion of their wishes. All subjects received psychometric testing (State-Trait Anxiety Inventory, STAI), an interview and routine counselling. Results: Twenty families were included. Twenty-four of the relatives could not be reached, 59 were 'decliners', 47 participated by the proband and 42 by the letter. Predictive testing was performed in 98 % of the participants of which 30 were mutation carriers. The intervention is psychologically safe: the 95 % CI for the estimated mean difference in STAI DY1 between phase II/I subjects (mean difference -1.07, 95 % CI -4.4 to 2.35, p = 0.53) shows that the mean STAI DY1 score (measured at first consult) for phase II is no more than 2.35 units higher than for phase I, which is not relevant. Conclusions: A protocol directly informing relatives nearly doubles the number of relatives tested and is psychologically safe. This should lead to a change in counselling guidelines in families with a strong germline predisposition for cancer