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A peroxygenase-catalysed hydroxylation of organosilanes is reported. The recombinant peroxygenase from Agrocybe aegerita (AaeUPO) enabled efficient conversion of a broad range of silane starting materials in attractive productivities (up to 300â mM h-1 ), catalyst performance (up to 84â s-1 and more than 120 000 catalytic turnovers). Molecular modelling of the enzyme-substrate interaction puts a basis for the mechanistic understanding of AaeUPO selectivity.
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BACKGROUND/OBJECTIVES: Molluscum contagiosum is the most common skin infection in children. One topical treatment used for Molluscum contagiosum is potassium hydroxide. The objective of this study was to compare the efficacy of potassium hydroxide topical treatment at different concentrations with that of placebo in terms of complete clearing of Molluscum contagiosum lesions and to assess the safety and tolerance of potassium hydroxide topical treatment. METHODS: This was a double-blind randomized clinical trial of three treatments (potassium hydroxide 10%, potassium hydroxide 15%, placebo) applied once daily up to complete clearing of lesions (maximum duration 60 days) in 53 children aged 2-6 years in primary health care pediatric offices in Catalonia, Spain. RESULTS: In the intention-to-treat analysis, potassium hydroxide 10% (58.8%, P = .03) and potassium hydroxide 15% (64.3%, P = .02) had efficacy superior to that of placebo (18.8%). The number of Molluscum contagiosum lesions was significantly reduced with potassium hydroxide 10% and 15%. The main efficacy outcome was achieved in 58.8% of children in the potassium hydroxide 10% group (P = .03 vs placebo) and in 64.3% of children in the potassium hydroxide 15% group (P = .02 vs placebo). Potassium hydroxide 10% and 15% were not significantly different in efficacy from each other. Potassium hydroxide 10% and placebo were better tolerated than potassium hydroxide 15%. No adverse events were reported during the study period. CONCLUSIONS: Potassium hydroxide 10% and 15% demonstrated high rates of efficacy in clearing Molluscum contagiosum lesions, with potassium hydroxide 10% being better tolerated.
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Hidróxidos/administração & dosagem , Molusco Contagioso/tratamento farmacológico , Compostos de Potássio/administração & dosagem , Administração Tópica , Criança , Pré-Escolar , Método Duplo-Cego , Humanos , Hidróxidos/efeitos adversos , Análise de Intenção de Tratamento , Masculino , Compostos de Potássio/efeitos adversos , Espanha , Resultado do TratamentoRESUMO
The development of convenient tools for describing and quantifying the effects of standard and novel therapeutic agents is essential for the research community, to perform more precise evaluations. Although mathematical models and quantification criteria have been exchanged in the last decade between different fields of study, there are relevant methodologies that lack proper mathematical descriptions and standard criteria to quantify their responses. Therefore, part of the relevant information that can be drawn from the experimental results obtained and the quantification of its statistical reliability are lost. Despite its relevance, there is not a standard form for the in vitro endpoint tumor cell lines' assays (TCLA) that enables the evaluation of the cytotoxic dose-response effects of anti-tumor drugs. The analysis of all the specific problems associated with the diverse nature of the available TCLA used is unfeasible. However, since most TCLA share the main objectives and similar operative requirements, we have chosen the sulforhodamine B (SRB) colorimetric assay for cytotoxicity screening of tumor cell lines as an experimental case study. In this work, the common biological and practical non-linear dose-response mathematical models are tested against experimental data and, following several statistical analyses, the model based on the Weibull distribution was confirmed as the convenient approximation to test the cytotoxic effectiveness of anti-tumor compounds. Then, the advantages and disadvantages of all the different parametric criteria derived from the model, which enable the quantification of the dose-response drug-effects, are extensively discussed. Therefore, model and standard criteria for easily performing the comparisons between different compounds are established. The advantages include a simple application, provision of parametric estimations that characterize the response as standard criteria, economization of experimental effort and enabling rigorous comparisons among the effects of different compounds and experimental approaches. In all experimental data fitted, the calculated parameters were always statistically significant, the equations proved to be consistent and the correlation coefficient of determination was, in most of the cases, higher than 0.98.
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Antineoplásicos/farmacologia , Colorimetria , Ensaios de Seleção de Medicamentos Antitumorais , Modelos Teóricos , Bioensaio , Linhagem Celular Tumoral , Determinação de Ponto Final , Células HeLa , Humanos , Células MCF-7 , Reprodutibilidade dos Testes , RodaminasRESUMO
Background: Insulin and insulin-like growth factor (IGF)-1 receptors are present in ocular tissues such as corneal epithelium, keratocytes, and conjunctival cells. Insulin plays a crucial role in the growth, differentiation, and proliferation of corneal epithelial cells, as well as in wound healing processes in various tissues. Purpose: This review explores the potential role of topical insulin in the treatment of ocular surface diseases. Specifically, it examines its impact on corneal nerve regeneration, sub-basal plexus corneal nerves, and its application in conditions like corneal epithelial defects, dry eye disease, and diabetic keratopathy. Methods: The review analyzes studies conducted over the past decade that have investigated the use of topical insulin in ocular surface diseases. It focuses on indications, drug preparation methods, side effects, efficacy outcomes, and variations in insulin concentrations and dosages used. Results: While off-label use of topical insulin has shown promising results in refractory corneal epithelial defects, its efficacy in dry eye disease is yet to be demonstrated. Variations in concentrations, dilutions, and dosing guidelines have been reported. However, limited data on ocular penetration, ocular toxicity, and systemic side effects pose challenges to its widespread utility. Conclusion: This review synthesizes findings from ocular investigations on topical insulin to assess its potential applicability in treating ocular surface and corneal diseases. By highlighting indications, preparation methods, side effects, and efficacy outcomes, it aims to provide insights into the current status and future prospects of using topical insulin in ophthalmic practice.
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Síndromes do Olho Seco , Insulina , Soluções Oftálmicas , Humanos , Insulina/administração & dosagem , Insulina/uso terapêutico , Síndromes do Olho Seco/tratamento farmacológico , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/uso terapêutico , Doenças da Córnea/tratamento farmacológico , Animais , Administração Oftálmica , Administração Tópica , Córnea/efeitos dos fármacos , Córnea/metabolismoRESUMO
BACKGROUND: Nurses have the potential to make a real impact on the health and well-being of people and populations and contribute to the realisation of delivery of Universal Health Coverage. However, in many parts of the world, the education and practice of nursing and nurses' position in health care and society are restricted by a range of social, cultural, economic and political factors. In North Macedonia, the Ministry of Health in partnership with the WHO Country Office launched a primary healthcare strategy supporting the development of nurses in primary care to fulfil their full scope of service. AIMS: To present information on the education, practice and position of nursing, in particular primary care nursing, in North Macedonia and to describe the ongoing initiatives to support the further development of nursing. APPROACH: Background documents reviewed, and visits to healthcare settings, organisations, interviews with individuals and groups and workshops undertaken in 2019-2020. FINDINGS: Three key areas of development were identified: education of nurses, their service delivery and practice in primary care, and their position in health care and society, all underpinned by the need for workforce planning. The findings formed the basis of a 10-year plan: Making Change Happen: The Nursing and Midwifery Development Roadmap. DEVELOPMENTS: To support the proposed primary care pilots, during the 2020/2021 COVID-19 pandemic, an on-line modular programme for primary care nurses was developed and delivered with the support of members drawn from The National Working Group for Moving Primary Care Nursing Forward in North Macedonia. Further work is planned to develop initial nurse education and to pilot changes in primary care. CONCLUSIONS: The launch of the primary healthcare strategy stimulated initiatives to improve the education, position and practice of primary care nursing. The COVID-19 pandemic required flexibility and changes to the original plans.
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COVID-19 , Enfermagem de Atenção Primária , Humanos , República da Macedônia do Norte , Pandemias , Atenção à SaúdeRESUMO
Immune-checkpoint inhibitors (ICIs) are antagonists of inhibitory receptors in the immune system, such as the cytotoxic T-lymphocyte-associated antigen-4, the programmed cell death protein-1 and its ligand PD-L1, and they are increasingly used in cancer treatment. By blocking certain suppressive pathways, ICIs promote T-cell activation and antitumor activity but may induce so-called immune-related adverse events (irAEs), which mimic traditional autoimmune disorders. With the approval of more ICIs, irAE prediction has become a key factor in improving patient survival and quality of life. Several biomarkers have been described as potential irAE predictors, some of them are already available for clinical use and others are under development; examples include circulating blood cell counts and ratios, T-cell expansion and diversification, cytokines, autoantibodies and autoantigens, serum and other biological fluid proteins, human leucocyte antigen genotypes, genetic variations and gene profiles, microRNAs, and the gastrointestinal microbiome. Nevertheless, it is difficult to generalize the application of irAE biomarkers based on the current evidence because most studies have been retrospective, time-limited and restricted to a specific type of cancer, irAE or ICI. Long-term prospective cohorts and real-life studies are needed to assess the predictive capacity of different potential irAE biomarkers, regardless of the ICI type, organ involved or cancer site.
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Several factors have been associated with the occurrence of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) therapy. Despite their availability, the predictive value of circulating blood cell parameters remains underexplored. Our aim was to investigate whether baseline values of and early changes in absolute neutrophil count (ANC), absolute lymphocyte count (ALC), other blood cell counts, and lymphocyte-related ratios can predict irAEs and whether sex may differentially influence this potential predictive ability. Of the 145 patients included, 52 patients (35.8%) experienced at least one irAE, with a 1-year cumulative incidence of 41.6%. Using Fine and Gray competing risk models, we identified female sex (hazard ratio (HR) = 2.17, 95% confidence interval (CI) = 1.20-3.85), high ALC before ICI initiation (HR = 1.63, 95% CI = 1.09-2.45), and low ANC after ICI initiation (HR = 0.81, 95% CI = 0.69-0.96) as predictors of irAEs. However, ALC and ANC may only have an impact on the risk of irAEs in women (stratified for female sex, ALC-related HR = 2.61, 95% CI = 1.40-4.86 and ANC-related HR = 0.57, 95% CI = 0.41-0.81). Priority should be given to developing models to predict ICI-related toxicity and their validation in various settings, and such models should assess the impact of patient sex on the risk of toxicity.
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Extracorporeal life support is a well-known therapy for acute respiratory failure. Its use has increased exponentially in recent years, even more since the beginning of the SARS-CoV-2 pandemic. Patients with COVID-19 may need long-term extracorporeal life support runs. They also suffer coagulation derangements that cause a prothrombotic state. Both situations may increase the need for exchanges of extracorporeal life support circuits. Extracorporeal life support circuit exchange should be performed as quickly and as safely as possible because patients may be completely dependent on it.
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COVID-19 , Oxigenação por Membrana Extracorpórea , Síndrome do Desconforto Respiratório , Humanos , Estudos Retrospectivos , SARS-CoV-2RESUMO
Introduction: Immune checkpoint inhibitor (ICI) therapy is markedly improving the prognosis of patients with several types of cancer. On the other hand, the growth in the use of these drugs in oncology is associated with an increase in multiple immune-related adverse events (irAEs), whose optimal prevention and management remain unclear. In this context, there is a need for reliable and validated biomarkers to predict the occurrence of irAEs in patients treated with ICIs. Thus, the main objective of this study is to evaluate the diagnostic performance of a sensitive routinely available panel of autoantibodies consisting of antinuclear antibodies, rheumatoid factor, and antineutrophil cytoplasmic antibodies to identify patients at risk of developing irAEs. Methods and Analysis: A multicenter, prospective, observational, cohort study has been designed to be conducted in patients diagnosed with cancer amenable to ICI therapy. Considering the percentage of ICI-induced irAEs to be 25% and a loss to follow-up of 5%, it has been estimated that a sample size of 294 patients is required to detect an expected sensitivity of the autoantibody panel under study of 0.90 with a confidence interval (95%) of no less than 0.75. For 48 weeks, patients will be monitored through the oncology outpatient clinics of five hospitals in Spain. Immune-related adverse events will be defined and categorized according to CTCAE v. 5.0. All the patients will undergo ordinary blood tests at specific moments predefined per protocol and extraordinary blood tests at the time of any irAE being detected. Ordinary and extraordinary samples will be frozen and stored in the biobank until analysis in the same autoimmunity laboratory when the whole cohort reaches week 48. A predictive model of irAEs will be constructed with potential risk factors of immune-related toxicity including the autoantibody panel under study. Ethics and Dissemination: This protocol was reviewed and approved by the Ethical Committee of the Basque Country and the Spanish Agency of Medicines and Medical Devices. Informed consent will be obtained from all participants before their enrollment. The authors declare that the results will be submitted to an international peer-reviewed journal for their prompt dissemination.
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BACKGROUND: Molluscum contagiosum is a non-severe pediatric viral infection. Because it is highly contagious and current treatments have negative aesthetic and psychological effects, we want to test an alternative treatment in the primary care setting, consisting of two different concentrations of potassium hydroxide solution. METHODS/DESIGN: The study design is a double-blind, randomized clinical trial, using three types of topical treatment. The treatment consist of daily applications of potassium hydroxide (KOH) in aqueous solution at 10% and 15% concentration, and a placebo administered in the control group. Four follow-up visits (at 15, 30, 45 and 60 days) are planned to evaluate treatment effectiveness and patient tolerance. The main outcome measure of the trial will be the healing rate, defined as lesion disappearance in the affected zones after the topic application of the experimental treatment. Secondary measures will be the principal characteristics and evolution of the affected zone (surface area, number of lesions, size and density of lesions), treatment tolerance (hyperpigmentation, itching, burning, pain), recurrence rate and the natural evolution of lesions in the control group. DISCUSSION: KOH can potentially be an effective and safe treatment for MC in primary care, and can also reduce referrals to dermatologists and hospital pediatric departments. In addition, KOH may be a valid and less expensive alternative to current invasive treatments (surgical excision).
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Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/efeitos adversos , Hidróxidos/administração & dosagem , Hidróxidos/efeitos adversos , Molusco Contagioso/tratamento farmacológico , Compostos de Potássio/administração & dosagem , Compostos de Potássio/efeitos adversos , Administração Tópica , Criança , Pré-Escolar , Protocolos Clínicos , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Humanos , Molusco Contagioso/patologia , Placebos/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: The aim of this study was to assess the diagnostic performance of an autoantibody battery in patients receiving immune checkpoint inhibitors who experienced immune-related adverse events (irAEs). METHODS: We retrospectively analyzed several variables potentially related to irAEs, namely, demographic, clinical, and laboratory characteristics, including an autoantibody battery (antinuclear, anti-neutrophil cytoplasmic, anti-thyroid antibodies and rheumatoid factor). RESULTS: Sixty-nine patients (48 men; 61.8 ± 10.9 years at baseline) diagnosed with stage-4 solid-organ cancer and treated with nivolumab were followed up for 12 ± 10.3 months. Thirty-two irAEs were detected in 26 patients (37.5%). Adverse events occurred more commonly in women (62% vs. 27%, p = .006), and younger patients (irAEs: 58.1 ± 9.8, no irAEs: 64.1 ± 10.9 years, p = .024). Autoantibody battery results were available for 26 patients and were more frequently positive in patients with irAEs (87% vs. 30%, p = .009). The positive predictive value, negative predictive value, and diagnostic accuracy of the battery were 82.3%, 77.8%, and 80.8%, respectively. Among the 64 patients with an evaluable response, 23 (38.5%) experienced tumour progression, this being less frequent in patients with irAEs (19% vs. 48.5%, p = .03). Overall survival was higher in patients developing irAEs (HR = 1.88, p = .05). CONCLUSION: Positivity in a readily available autoantibody battery may be associated with the occurrence of irAEs.KEY MESSAGESPositivity in an accessible and inexpensive autoantibody battery including antinuclear, anti-neutrophil cytoplasmic, anti-thyroid antibodies and rheumatoid factor may be associated with the occurrence of immune-related adverse events.Patients with cancer on immune checkpoint inhibitors experiencing immune-related adverse events showed a lower risk of progression and better overall survival than patients not experiencing this type of adverse effect.
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Antineoplásicos Imunológicos , Autoanticorpos , Neoplasias , Antineoplásicos Imunológicos/efeitos adversos , Feminino , Humanos , Inibidores de Checkpoint Imunológico , Masculino , Neoplasias/tratamento farmacológico , Nivolumabe/efeitos adversos , Estudos Retrospectivos , Fator ReumatoideRESUMO
OBJECTIVES: To our knowledge no previous study has assessed the performance of a rapid antigen diagnostic immunoassay (RAD) conducted at the point of care (POC). We evaluated the Panbio™ COVID-19 Ag Rapid Test Device for diagnosis of coronavirus 2019 disease (COVID-19) in symptomatic patients (n = 412) attending primary healthcare centres. METHODS: RAD was performed immediately after sampling following the manufacturer's instructions (reading at 15 min). RT-PCRs were carried out within 24 h of specimen collection. Samples displaying discordant results were processed for culture in Vero E6 cells. Presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in cell cultures was confirmed by RT-PCR. RESULTS: Out of 412 patients, 43 (10.4%) tested positive by RT-PCR and RAD, and 358 (86.9%) tested negative by both methods; discordant results (RT-PCR+/RAD-) were obtained in 11 patients (2.7%). Overall specificity and sensitivity of rapid antigen detection (RAD) was 100% (95%CI 98.7-100%) and 79.6% (95%CI 67.0-88.8%), respectively, taking RT-PCR as the reference. Overall RAD negative predictive value for an estimated prevalence of 5% and 10% was 99% (95%CI 97.4-99.6%) and 97.9% (95%CI 95.9-98.9), respectively. SARS-CoV-2 could not be cultured from specimens yielding RT-PCR+/RAD- results (n = 11). CONCLUSION: The Panbio™ COVID-19 Ag Rapid Test Device performed well as a POC test for early diagnosis of COVID-19 in primary healthcare centres. More crucially, the data suggested that patients with RT-PCR-proven COVID-19 testing negative by RAD are unlikely to be infectious.
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Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , Testes Imediatos , SARS-CoV-2/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Instituições de Assistência Ambulatorial , Antígenos Virais/análise , Teste de Ácido Nucleico para COVID-19 , Criança , Pré-Escolar , Diagnóstico Precoce , Feminino , Humanos , Imunoensaio , Lactente , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Kit de Reagentes para Diagnóstico , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Sensibilidade e Especificidade , Adulto JovemRESUMO
INTRODUCTION: Patients with cancer may be at increased risk of more severe COVID-19 disease; however, prognostic factors are not yet clearly identified. The GRAVID study aimed to describe clinical characteristics, outcomes, and predictors of poor outcome in patients with lung cancer and COVID-19. METHODS: Prospective observational study that included medical records of patients with lung cancer and PCR-confirmed COVID-19 diagnosis across 65 Spanish hospitals. The primary endpoint was all-cause mortality; secondary endpoints were hospitalization and admission to intensive care units (ICU). RESULTS: A total of 447 patients with a mean age of 67.1 ± 9.8 years were analysed. The majority were men (74.3 %) and current/former smokers (85.7 %). NSCLC was the most frequent type of cancer (84.5 %), mainly as adenocarcinoma (51.0 %), and stage III metastatic or unresectable disease (79.2 %). Nearly 60 % of patients were receiving anticancer treatment, mostly first-line chemotherapy. Overall, 350 (78.3 %) patients were hospitalized for a mean of 13.4 ± 11.4 days, 9 (2.0 %) were admitted to ICU and 146 (32.7 %) died. Advanced disease and the use of corticosteroids to treat COVID-19 during hospitalization were predictors of mortality. Hospitalized, non-end-of-life stage patients with lymphocytopenia and high LDH had an increased risk of death. Severity of COVID-19 correlated to higher mortality, ICU admission, and mechanical ventilation rates. CONCLUSIONS: Mortality rate was higher among patients treated with corticosteroids during hospitalization, while anticancer therapy was not associated with an increased risk of hospitalization or death. Tailored approaches are warranted to ensure effective cancer management while minimizing the risk of exposure to SARS-CoV-2.
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COVID-19 , Neoplasias Pulmonares , Idoso , Teste para COVID-19 , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Espanha/epidemiologiaRESUMO
In this study, the antibacterial activities of a bovine Lactoferrin pepsin hydrolysate (LFH) and a synthetic peptide derived from bovine lactoferricin (LfcinB(17-31)) have been evaluated against Oenococcus oeni and three additional lactic acid bacteria (LAB) known to cause spoilage during winemaking processes. Inhibition of bacterial growth was demonstrated in vitro in synthetic broth media (MRS) for both LFH and LfcinB(17-31). The bactericidal activity of the synthetic peptide was also assayed and found to vary depending on the bacterial species and the matrix in which exposure to peptide occurred (either MRS broth or white must). Specificity of LfcinB(17-31) for Lactobacillus brevis, Pediococcus damnosus, and O. oeni was demonstrated in must fermentation experiments in which these three LAB co-existed with the winemaking Saccharomyces cerevisiae T73 in the presence of the peptide. Finally, fermentation experiments also showed that LfcinB(17-31) at inhibitory concentrations did not alter either fermentation kinetics or specific enological parameters.
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Antibacterianos/farmacologia , Lactobacillaceae/efeitos dos fármacos , Lactoferrina/farmacologia , Fragmentos de Peptídeos/farmacologia , Vinho/microbiologia , Animais , Bovinos , Contagem de Colônia Microbiana , Qualidade de Produtos para o Consumidor , Fermentação , Contaminação de Alimentos/prevenção & controle , Cinética , Leuconostoc/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pediococcus/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos dos fármacos , Especificidade da EspécieRESUMO
The antimicrobial action of lactoferrin (LF)-derived peptides against Dekkera bruxellensis strains isolated from spoiled wines has been examined. The study included a fifteen-residue peptide (LfcinB(17-31)) derived from bovine lactoferricin B and a bovine LF pepsin hydrolysate (LFH). In vitro assays showed the inhibitory properties of LfcinB(17-31) on D. bruxellensis growth with IC(50) and MIC values in the micromolar range. Strains tested showed different sensitivity to the peptide. LfcinB(17-31) showed fungicidal properties towards all strains tested in laboratory growth medium. However, the extent of fungicidal activity was strain-dependent in must and wine, confirming the different antimicrobial action of peptides depending on both the food matrix and the target micro-organism. The binding of LfcinB(17-31) to D. bruxellensis cells was visualized by fluorescence microscopy and correlated with the fungicidal activity in the different matrixes. LfcinB(17-31) and LFH showed growth inhibitory properties in wine suggesting their potential use for spoilage control.
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Antifúngicos/farmacologia , Dekkera/efeitos dos fármacos , Lactoferrina/farmacologia , Fragmentos de Peptídeos/farmacologia , Vinho/microbiologia , Animais , Bovinos , Contagem de Colônia Microbiana , Qualidade de Produtos para o Consumidor , Dekkera/crescimento & desenvolvimento , Contaminação de Alimentos/prevenção & controle , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Advancements in open and endovascular techniques have brought a widespread indication of revascularization in the majority of patients with critical limb ischemia (CLI). However, some cases still have a dismal short-term outcome. Identifying preoperative variables that characterize these patients could be important to prevent futile decisions. The aim of this study was to define predictive risk factors of mortality and/or major amputation after revascularization for CLI. METHODS: Retrospective study of 515 consecutive patients (mean age=73 years; 73% males) undergoing open (N.=228; 44.3%) or endovascular (N.=287; 55.7%) surgery for CLI between 2005 and 2015. Neither redo-procedures (ipsilateral or contralateral) nor acute limb ischemia patients were included as new cases. RESULTS: Thirty-day amputation, mortality or combined event rates were 1.4% (N.=7), 4.5% (N.=23) and 5.6% (N.=29), while at 90 days were 4.1 (N.=21), 9.1% (N.=47) and 12.8% (N.=66), respectively. We found no significant differences between open or endovascular surgery. Risk factors associated with a 90-day combined event were age (OR=1.04, P=0.014), preoperative hemoglobin (OR=0.80; P=0.003), history of acute myocardial infarction (OR=2.68; P=0.007), ischemic ulcers (OR=2.57; P=0.014) and below-the-knee revascularization (OR=2.20; P=0.007). The discrimination of the model was good (area under ROC curve=0.75). Model predicted probabilities of the combined death and/or lower limb major amputation end-point ranged (95% interval) from 1.1% to 38.1%. CONCLUSIONS: Certain preoperative variables can predict satisfactorily the short-term outcome after revascularization for CLI, although they are not sufficiently useful to identify the patient in whom revascularization can be clearly futile. Further research is needed to refine a predictive model suitable for decision-making.
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Procedimentos Endovasculares/efeitos adversos , Isquemia/cirurgia , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/cirurgia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Tomada de Decisão Clínica , Estado Terminal , Técnicas de Apoio para a Decisão , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Isquemia/diagnóstico , Isquemia/fisiopatologia , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/mortalidadeRESUMO
The antimicrobial action of selected short synthetic peptides against wine spoilage yeasts such as Cryptococcus albidus, Dekkera bruxellensis, Pichia membranifaciens, Saccharomyces cerevisiae, Zygosaccharomyces bailii and Zygosaccharomyces bisporus has been examined. Peptides analyzed include nine sequence-related antifungal hexapeptides (PAFs) previously developed by a combinatorial approach, and two representative lactoferricin B (LfcinB)-derived peptides. Different peptides had distinct activity profiles. In vitro assays identified the peptides PAF26, PAF36, and LfcinB(17-31), as having growth inhibitory properties towards several of the yeasts at low micromolar concentrations. Z. bailii and Z. bisporus were the most sensitive yeasts. In addition to their fungistatic activity, the three peptides showed fungicidal properties towards Z. bailii, Z. bisporus, and S. cerevisiae in laboratory growth medium. Remarkably, only LfcinB(17-31) against Z. bisporus had inhibitory and fungicidal properties in wine at the concentrations assayed, showing that the antimicrobial action of each peptide is dependent on both the food matrix and the target micro-organism. Lack of fungicidal activity of peptides against Z. bailii in wine is related to the presence of salt ions other than divalent cations. On the contrary, fungicidal activity of LfcinB(17-31) towards Z. bisporus was not significantly affected by wine salts. Our data identify a bioactive peptide from natural origin with potential use against the food spoilage yeast Z. bisporus, and indicate that the application of antimicrobial peptides in wine preservation deserves further investigation.
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Antifúngicos/farmacologia , Contaminação de Alimentos , Fragmentos de Peptídeos/farmacologia , Vinho/microbiologia , Leveduras/efeitos dos fármacos , Contagem de Colônia Microbiana , Qualidade de Produtos para o Consumidor , Humanos , Lactoferrina/farmacologia , Testes de Sensibilidade Microbiana , Oligopeptídeos/farmacologia , Leveduras/crescimento & desenvolvimentoRESUMO
PURPOSE: Fast identification of bacteria directly from positive blood cultures (BCs) by matrix-assisted laser desorption/ionization time-of-flight mass-spectrometry (MALDI-TOF MS) can be achieved either using the MALDI Sepsityper kit (protein extraction method) or after a short-term pre-cultivation step on solid medium. We developed a new method that involves short-term enrichment of positive BCs in brain-heart infusion broth (BHI) prior to MALDI-TOF MS analysis. METHODOLOGY: Eighty-four BCs flagged as positive were included in this study; these were processed in parallel either directly using the MALDI Sepsityper kit or following a short-term culture either in BHI or on Columbia blood agar with 5â% sheep blood (CBA). RESULTS: Bacterial species were successfully identified in 91.6, 89.2 and 65.4â% of cases after pre-cultivation for 4 h in BHI, on CBA, or by using the MALDI Sepsityper kit, respectively. Overall, the mean incubation time to correct identification was shorter when pre-cultures were performed in BHI; the mean time for Gram-negative rods was 78.2 min in BHI and 108.2 min on CBA (P=0.045), and the mean time for Gram-positive cocci was 128.5 min in BHI and 169.6 min on CBA (P=0.013). CONCLUSION: Short-term enrichment of BCs in BHI accelerates identification of a number of bacterial species by MALDI-TOF MS. Further prospective studies are needed to validate our method and gauge its potential clinical impact on the management of bloodstream bacterial infections.
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Hemocultura , Meios de Cultura/química , Bactérias Gram-Negativas/isolamento & purificação , Cocos Gram-Positivos/isolamento & purificação , Infecções Bacterianas/diagnóstico , Técnicas Bacteriológicas , Humanos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
INTRODUCTION AND OBJECTIVES: The objective of this study was to determine whether a home-based intervention can reduce mortality and hospital readmissions and improve quality of life in patients with heart failure. METHODS: A randomized clinical trial was carried out between January 2004 and October 2006. In total, 283 patients admitted to hospital with a diagnosis of heart failure were randomly allocated to a home-based intervention (intervention group) or usual care (control group). The primary end-point was the combination of all-cause mortality and hospital readmission for worsening heart failure at 1-year follow-up. RESULTS: The primary end-point was observed in 41.7% of patients in the intervention group and in 54.3% in the control group. The hazard ratio was 0.70 (95% confidence interval [CI] 0.55-0.99). Taking significant clinical variables into account slightly reduced the hazard ratio to 0.62 (95% CI 0.50-0.87). At the end of the study, the quality of life of patients in the intervention group was better than in the control group (18.57 vs. 31.11; P< .001). CONCLUSIONS: A home-based intervention for patients with heart failure reduced the aggregate of mortality and hospital readmissions and improved quality of life.