T-cell activation and bacterial infection in skin wounds of recessive dystrophic epidermolysis bullosa patients.

Recessive dystrophic epidermolysis bullosa (RDEB) patients develop poorly healing skin wounds that are frequently colonized with microbiota. Because T cells play an important role in clearing such pathogens, we aimed to define the status of adaptive T cell-mediated immunity in RDEB wounds. Using a non-invasive approach for sampling of wound-associated constituents, we evaluated microbial contaminants in cellular fraction and exudates obtained from RDED wounds. Infectivity and intracellular trafficking of inactivated Staphylococcus aureus was accessed in RDEB keratinocytes. S. aureus and microbial antigen-specific activation of RDEB wound-derived T cells were investigated by fluorescence-activated cell sorting-based immune-phenotyping and T-cell functional assays. We found that RDEB wounds and epithelial cells are most frequently infected with Staphylococcus sp. and Pseudomonas sp. and that S. aureus essentially infects more RDEB keratinocytes and RDEB-derived squamous cell carcinoma cells than keratinocytes from healthy donors. The RDEB wound-associated T cells contain populations of CD4+ and CD8+ peripheral memory T cells that respond to soluble microbial antigens by proliferating and secreting interferon gamma (IFNγ). Moreover, CD8+ cytotoxic T lymphocytes recognize S. aureus-infected RDEB keratinocytes and respond by producing interleukin-2 (IL-2) and IFNγ and degranulating and cytotoxically killing infected cells. Prolonged exposure of RDEB-derived T cells to microbial antigens in vitro does not trigger PD-1-mediated T-cell exhaustion but induces differentiation of the CD4high population into CD4high CD25+ FoxP3+ regulatory T cells. Our data demonstrated that adaptive T cell-mediated immunity could clear infected cells from wound sites, but these effects might be inhibited by PD-1/Treg-mediated immuno-suppression in RDEB.

[Pet ownership in inmunocompromised patients: update and veterinary and medical considerations]. / Tenencia de mascotas en pacientes inmunocomprometidos: actualización y consideraciones veterinarias y médicas.

Pet ownership offers undisputed benefits to immunocompromised (IC) patients, however, it poses the risk for potentially serious zoonoses. Mechanisms of transmission and manifestation of major zoonotic infections in dogs and cats that may affect IC patients are described. We also provide updated international information and local data. Recommendations are given to choose and care for pets ensuring safe and responsible ownership. This will help to prevent, detect and treat infections timely.

[Recommendations for the diagnosis and treatment of urinary tract infection in pediatrics. Part 2: Working group associated with the Antimicrobial Committee, Chilean Society of Infectology]. / Recomendaciones para diagnóstico y tratamiento de la infección del tracto urinario en pediatría. Parte 2: Grupo de trabajo asociado al Comité de Antimicrobianos, Sociedad Chilena de Infectología (SOCHINF).

The urinary tract infection (UTI) is one of the most common bacterial infections in childhood. An adequate diagnosis is essential to be able to carry out a rational, efficient and effective treatment, however, there is great heterogeneity in diagnostic methods, specifically in the study of antimicrobial susceptibility. The aim of these recommendations is to provide tools to homogenize the diagnosis criteria, susceptibility study and antimicrobial treatment of urinary tract infection in the pediatric population, with a rational use of antibiotics approach. In the first part, the recommendations regarding diagnosis were presented, such as sampling and cut-off points, as well as microbiological considerations for susceptibility study and management of UTI in pediatrics. This second part details the management of complications, UTI in special situations, and pharmacokinetic and pharmacodynamic considerations of antimicrobials to be prescribed in UTI.

[Recommendations for the diagnosis and treatment of urinary tract infection in pediatrics. Part 1: Working group associated with the Antimicrobial Committee, Chilean Society of Infectology]. / Recomendaciones para diagnóstico y tratamiento de la infección del tracto urinario en pediatría. Parte 1: Grupo de trabajo asociado al Comité de Antimicrobianos, Sociedad Chilena de Infectología (SOCHINF).

The urinary tract infection (UTI) is one of the most common bacterial infections in childhood. An adequate diagnosis is essential to be able to carry out a rational, efficient and effective treatment, however, there great heterogeneity in diagnostic methods, specifically in the study of antimicrobial susceptibility. The aim of these recommendations is to provide tools to homogenize the diagnosis criteria, susceptibility study and antimicrobial treatment of urinary tract infection in the pediatric population, with a rational use of antibiotics approach. In the first part, the recommendations regarding diagnosis are presented, such as sampling and cut-off points, as well as microbiological considerations for susceptibility study and management of UTI in pediatrics. The second part details the management of complications, UTI in special situations, and pharmacokinetic and pharmacodynamic considerations of antimicrobials to be prescribed in UTI.

Relevance of codetection of respiratory viruses in the severity of acute respiratory infection in hospitalized children. / Relevancia de la co-detección de virus respiratorios en la severidad de la infección respiratoria aguda en niños hospitalizados.

INTRODUCTION: Multiplex polymerase chain reaction (PCR) allows simultaneous detection of respiratory viruses, raising questions about their relevance in the clinical feature. OBJECTIVE: To evaluate the contribution of clinical, epidemiological, and virological factors in the clinical course of children hospitalized due to ARI with viral co-detection. PATIENTS AND METHOD: Pediatric patients ≤ 15 years old, hospitalized due to ARI at the UC-CHRISTUS Health Network Clinical Hospital between June and October 2014, and who presented a positive respiratory molecular panel test, were included. Respiratory samples (nasopharyngeal swab, tracheal aspiration, or bronchoalveolar lavage) with positive panel tests by Seeplex® RV15 OneStep ACE Detection Seegene® technique, were analyzed with a second technique (xTAG-RVP-FASTv2 Luminex®, USA), which allows simultaneous and semi-quantitative detection of 17 respiratory viruses. Clinical and epidemiological records were collected. RESULTS: One virus was identified in 42/57 children (74%) and two or more in 15/57 (26%). Intensive care unit (ICU) hospi talization was significantly more frequent in patients with viral co-detection (OR = 5,5; IC 95%: 1,5 19,6). The most frequently detected viruses were rhinovirus/enterovirus (HRV/EV) (29%) and res piratory syncytial virus (RSV) (25%), and the most common co-detection was HRV/EV-RSV (33%). In x-rays, patients with HRV/EV infection presented interstitial images more frequently, while RSV was associated with condensations (p = 0.002). For HRV/EV, median fluorescence intensity (MFI, semi-quantification) were 1788 and 2456 in co-detection and single agent, respectively (p = 0.022). Children with HRV/EV co-detection had a longer hospital stay compared to isolated identification (5 versus 3 days, p = 0,028). CONCLUSION: In children hospitalized due to ARI, viral co-detection is frequent and associated with more ICU hospitalizations. Our study highlights the presence of HRV/ EV in viral co-detection and longer length of stay. More studies are needed to define the relevance of viral co-detection in hospitalized pediatric patients.

[Bartonella henselae with atypical infection and neuroretinitis in a pediatric unit: report of three cases]. / Infección atípica y neurorretinitis por Bartonella henselae en una unidad de hospitalización pediátrica: comunicación de tres casos.

Bartonella henselae is cat scratch disease's etiological agent, which is considered an endemic infection in Chile. It typically presents as a self-limited regional lymphadenopathy and less frequently with systemic involvement and extranodal or atypical manifestations: hepatosplenic, ocular or musculoskeletal involvement, among others. We present three cases of atypical cat scratch disease with ocular compromise, as neurorretinitis. This review highlights the importance of the active search for ocular complications in patients with disseminated cat scratch disease, leading to possible change in treatment and prognosis of the disease.

Aberrant recruitment of leukocytes defines poor wound healing in patients with recessive dystrophic epidermolysis bullosa.

BACKGROUND: Poorly healing wounds are one of the major complications in patients suffering from recessive dystrophic epidermolysis bullosa (RDEB). At present, there are no effective means to analyze changes in cellular and molecular networks occurring during RDEB wound progression to predict wound outcome and design betted wound management approaches. OBJECTIVES: To better define mechanisms influencing RDEB wound progression by evaluating changes in molecular and cellular networks. METHODS: We developed a non-invasive approach for sampling and analysis of wound-associated constituents using wound-covering bandages. Cellular and molecular components from seventy-six samples collected from early, established and chronic RDEB wounds were evaluated by FACS-based immuno-phenotyping and ELISA. RESULTS: Our cross-sectional analysis determined that progression of RDEB wounds to chronic state is associated with the accumulation (up to 90 %) of CD16+CD66b+ mature neutrophils, loss of CD11b+CD68+ macrophages, and a significant increase (up to 50 %) in a number of CD11c+CD80+CD86+ activated professional antigen presenting cells (APC). It was also marked by changes in activated T cells populations including a reduction of CD45RO+ peripheral memory T cells from 80 % to 30 % and an increase (up to 70 %) in CD45RA+ effector T cells. Significantly higher levels of MMP9, VEGF-A and cathepsin G were also associated with advancing of wounds to poorly healing state. CONCLUSIONS: Our data demonstrated that wound-covering bandages are useful for a non-invasive sampling and analysis of wound-associated constituents and that transition to poorly healing wounds in RDEB patients as associated with distinct changes in leukocytic infiltrates, matrix-remodeling enzymes and pro-angiogenic factors at wound sites.

Stem cells and oral surgery: A systematic review.

BACKGROUND: Considering the structural loss that occurs after surgical procedures for cystic and tumoral pathology, in periodontitis, as well as the maxillary atrophy that determines the rehabilitation with dental implants, it is imperative to find satisfactory solutions. The opportunity provided by the findings in stem cells is a recent introduction in the field of oral surgery, based on the regenerative potential that these cells possess in order to restore defects at different levels of the oral cavity. The aim of this systematic review is to discover the real applications that stem cells may have in our treatments in the near future. MATERIAL AND METHODS: We made a systematic review of the literature on the subject of stem cells to know the publications relating to them in the field of oral surgery since 2000. PRISMA statement was accomplished, as its official flow chart is used. RESULTS: This article draws clinical conclusions from basic research and those conducted in the first clinical cases to apply them in a short period of time to our patients in order to achieve excellence in regenerative therapies. CONCLUSIONS: To summarize, stem cells may be a turning point in tissue regeneration, though the major challenge is to overcome the remaining obstacles before they become a realistic therapeutic alternative. Key words:Stem cells, oral surgery, cell therapy, regeneration.

Cálculo de los Días de Terapia Antimicrobiana (DOT) en Cuidados Intensivos Pediátricos: una propuesta de metodología basada en el sistema informático de dispensación de medicamentos / Days of Antimicrobial Therapy (DOT) calculation in Pediatric Intensive Care: a methodology proposal based on the electronic records from the pharmacy dispensation system

INTRODUCCIÓN: El método recomendado para la medición de consumo de antimicrobianos (AMB) en pediatría es el cálculo del indicador Días de Terapia estandarizado por ocupación (DOT-std). Sin embargo, en hospitales que no cuentan con fichas electrónicas, obtener el numerador de los días de terapia (DOT) requiere revisión directa de las indicaciones del paciente, dificultando su aplicabilidad. OBJETIVOS: Validar el sistema de registros electrónicos de dispensación de medicamentos desde farmacia como fuente para el cálculo de DOT y DOT-std en la Unidad de Cuidados Intensivos Pediátrica (UCIP). MATERIALES Y MÉTODOS: Se revisaron las prescripciones de AMB desde la ficha clínica (método manual) y se compararon con los registros de dispensación de AMB a la UCIP (método informático) obtenidos del sistema de medicamentos de farmacia. Se evaluó la concordancia entre los DOT obtenidos mediante el Coeficiente de Correlación Intraclase. RESULTADOS: Los AMB más utilizados fueron vancomicina, meropenem y piperacilina/tazobactam. En 9 de 12 AMB se encontró concordancia significativa entre ambos métodos. CONCLUSIONES: Tras un proceso de validación local, los registros del sistema informático de dispensación de medicamentos desde farmacia podrían utilizarse para el cálculo de DOT en pediatría en hospitales que no cuenten con una ficha electrónica que permita su cálculo directo.

BACKGROUND: The recommended indicator for measuring antimicrobial (AMB) consumption in pediatric patients is the Days of Therapy indicator (DOT), which is then standardized by hospital occupancy rates (DOT-std). However, in hospitals that do not have electronic health records, obtaining the DOT requires a direct review of each pharmacological indication, which is not feasible in the long term. AIMS: To validate electronic records from the pharmacy dispensation system as a source for calculating DOT and estimating DOT-std in a Pediatric Intensive Care Unit (PICU). METHODS: AMB prescriptions at the PICU of a university hospital were directly reviewed (manual method) and compared with AMB dispensation records (computer method) obtained from the hospital pharmacy system. The Intraclass Correlation Coefficient was used to evaluate the agreement between the DOT obtained by both methods. RESULTS: The most used AMB were vancomycin, meropenem, and piperacillin/tazobactam. A significant agreement between the DOT obtained by using manual and computer methods was found in 9 of 12 evaluated AMB. CONCLUSIONS: After a local validation process, the electronic records of the pharmacy drug dispensation system could be considered a valid source for calculating DOT in PICUs in hospitals where electronic health records with prescription data are not yet available.

[Safety of fluoroquinolones: risks usually forgotten for the clinician]. / Seguridad de las fluoroquinolonas: riesgos habitualmente olvidados para el clínico.

Quinolones are a group of widely used antimicrobials. Although they are considered safe for patients, knowledge of the safety profile is necessary so that professionals become aware of what is necessary to monitor. At the musculoskeletal level, quinolones have the potential to damage cartilage, causing even tendon rupture in infrequent cases. Hypoglycemia / hyperglycemia has been observed at the endocrine level, thus, careful monitoring of glycemia in patients with quinolone is recommended in diabetic patients. At the cardiovascular level, arrhythmias induced by these antimicrobials are rare but severe. At the level of the nervous system, the appearance of alterations of the central nervous system and the peripheral neuropathy are emphasized. When assessing the safety of quinolones, it is important to consider potential interactions with other substances (medical products). In children it is preferred not to use fluoroquinolones because of the potential risk of cartilage damage and growth, effects that do not seem to be so dramatic in the face of new evidence. Despite optimism, the safety of the treatment of these antimicrobials should be evaluated in every pediatric patient.

Recomendaciones para diagnóstico y tratamiento de la infección del tracto urinario en pediatría. Parte 1: Grupo de trabajo asociado al Comité de Antimicrobianos, Sociedad Chilena de Infectología (SOCHINF) / Recommendations for the diagnosis and treatment of urinary tract infection in pediatrics. Part 1: Working group associated with the Antimicrobial Committee, Chilean Society of Infectology

Resumen La infección del tracto urinario (ITU) es una de las infecciones bacterianas más frecuentes en la infancia. Un adecuado diagnóstico es esencial para poder realizar un tratamiento racional, eficiente y eficaz; sin embargo, existe gran heterogeneidad en los métodos diagnósticos, específicamente en el estudio de la susceptibilidad antimicrobiana. El objetivo de estas recomendaciones es entregar herramientas para uniformar los criterios diagnósticos, el estudio de susceptibilidad bacteriana in vitro y el tratamiento antimicrobiano de la ITU en la población pediátrica, con un enfoque de uso racional de los antimicrobianos. En esta primera parte, se presentan las recomendaciones en cuanto a cómo obtener una adecuada muestra de orina, el diagnóstico de laboratorio incluyendo puntos de corte -unidades formadoras de colonias/mL de orina-, además de consideraciones microbiológicas para el estudio de susceptibilidad y finalmente, el manejo de la ITU en pediatría. En la segunda parte se detalla el tratamiento antimicrobiano de sus complicaciones, el manejo de ITU en situaciones especiales y consideraciones farmacocinéticas y farmacodinámicas de los antimicrobianos a indicar en ITU.

Abstract The urinary tract infection (UTI) is one of the most common bacterial infections in childhood. An adequate diagnosis is essential to be able to carry out a rational, efficient and effective treatment, however, there great heterogeneity in diagnostic methods, specifically in the study of antimicrobial susceptibility. The aim of these recommendations is to provide tools to homogenize the diagnosis criteria, susceptibility study and antimicrobial treatment of urinary tract infection in the pediatric population, with a rational use of antibiotics approach. In the first part, the recommendations regarding diagnosis are presented, such as sampling and cut-off points, as well as microbiological considerations for susceptibility study and management of UTI in pediatrics. The second part details the management of complications, UTI in special situations, and pharmacokinetic and pharmacodynamic considerations of antimicrobials to be prescribed in UTI.

Molecular characterization of feline Hepatozoon species from Brazil.

Feline Hepatozoon species from Brazil was molecular identified and characterized for the first time in São Paulo state, Brazil. Partial sequences of the 18S rRNA gene from the Hepatozoon from three naturally infected cats were analyzed. Sequences revealed that feline Hepatozoon was closely related to the canine Hepatozoon canis from Brazil.

Clinical assessment underestimates fat mass and overestimates resting energy expenditure in children with neuromuscular diseases.

BACKGROUND: Nutritional problems are frequent among patients with neuromuscular diseases, who consequently need an adequate evaluation. OBJECTIVE: to describe nutritional assessment and to estimate and measure body composition and energy requirement in children with neuromuscular diseases. SUBJECTS AND METHODS: We performed anthropometry, skinfold measurement and bioelectric impedance analysis (BIA) for estimate and measure, respectively, fat mass (FM). Resting energy expenditure (REE) was estimated by Schofield equations and measured by indirect calorimetry (IC). We compared actual energy intake with post-assessment recommendations. RESULTS: We studied 40 patients, 13.6 ± 3.3 years old (Range: 5.8-19.3), 80% boys, diagnosed with Duchenne Muscular Dystrophy (n = 21), other dystrophies (7), Muscular Spinal Atrophy (7), myopathies (3) and others (2). According to body mass index (BMI) 22.5% were well nourished (zBMI -1 to +1), 17.5% overweight (zBMI +1 to +2), 17.5% obese (zBMI ≥ +2), and 42.5% undernourished (zBMI < -1). Estimated FM was 20.2% (3.6-46.3), lower than BIA measurement: 34.2% (9.6-60.5) p < 0.001. Estimated REE was higher than measured REE: 1325 (813-2244) vs. 1202 (900-2100) kcal/day, p = 0.002. Actual energy intake: 1452 (1033-2476) was higher than recommended: 1300 (900-1900) kcal/day, p < 0.001. CONCLUSION: Undernutrition and overweight are prevalent in this group of children with neuromuscular diseases. Clinical assessment underestimates FM and overestimates REE.

[Surgical site infections in children undergoing cardiac surgery with delayed sternal closure: Case-control study]. / Infección del sitio quirúrgico en niños sometidos a cirugía cardíaca con cierre esternal diferido: Estudio de casos y controles.

INTRODUCTION: Surgical site infections (SSI) are an important cause of morbidity in pediatric cardiac surgery. Risk factors in patients requiring delayed sternal closure (DSC) are unknown. AIM: To report the rate of SSI in children undergoing cardiac surgery with DSC and determine the risk factors. METHODOLOGY: A retrospective case-control study, in patients younger than 15 years old undergoing cardiac surgery with DSC in our center between 2009 and 2010. SSI was diagnosed according to the criteria of the nosocomial infections committee of our institution, based on international recommendations. Univariate and multivariate analysis of variables was performed. A p < 0.05 was considered significant. RESULTS: 58 patients were included; the average age was 9.5 days. The most frequent diagnosis were transposition of the great arteries (36%) and hypoplastic left heart syndrome (27%). 13 patients had SSI (22%); 11 incisional and 2 mediastinitis. It was independently associated to SSI by-pass (BP) time longer than 200 min (OR adjusted = 9,53; IC 95% 1,37-66,35) and mechanical ventilation (MV) more than 5 days (OR adjusted = 8,98; IC 95% 1,16-69,40). CONCLUSION: The duration of BP and MV are risk factors of SSI in children undergoing cardiac surgery with DSC.

The role of serum biomarkers in the diagnosis and prognosis of oral cancer: A systematic review.

INTRODUCTION: Oral cancer is one of the causes of major morbidity and mortality in the world although incidence varies in the different geographical locations and races. Advances in molecular biology and cancer research have allowed elucidating serum biomarkers to improve diagnostic methods. The aim of this article systematic review is to highlight the utility and clinical value of serum biomarkers in the diagnosis and prognosis of oral cancer. MATERIAL AND METHODS: A systematic literature review using PubMed (MEDLINE databases) revealed a total of 140 articles related to this topic. Of those articles, 29 were included in the final review. We included articles published in English in the last five years, developed in human as cases and controls studies, retrospective or prospective studies and specific studies that analyzed a certain biomarker in serum. RESULTS: All of the studies include in this systematic review found significant differences in patients. Of those articles included, 2 used biomarkers to determinate cancerous phenotype, 11 mentioned their results were associated with worse prognosis and overall survival, 4 correlated biomarker concentration to clinical stages, 4 concluded it could be a helpful in diagnosis and 8 studies did not find a clear utility of the analysed biomarker. Due to differences in the presentation of data, meta-analysis was not possible. CONCLUSIONS: Biomarker use for diagnosis and prognosis is supported by clinical and scientific evidence is relevant. Nevertheless, after selecting a certain biomarker, monitoring protocols should be established in oral and maxillofacial surgeons teams so as we have a correct understanding of biological values. KEY WORDS: Serum biomarkers, oral cancer, diagnosis, prognosis.

Infección atípica y neurorretinitis por Bartonella henselae en una unidad de hospitalización pediátrica: comunicación de tres casos / Bartonella henselae with atypical infection and neuroretinitis in a pediatric unit: report of three cases

Resumen Bartonella henselae es el agente etiológico de la enfermedad por arañazo de gato (EAG), infección endémica en Chile. Típicamente se presenta como una linfadenopatía regional autolimitada y menos frecuentemente con compromiso sistémico y manifestaciones extraganglionares: en hígado, bazo, hueso, ojo, entre otros. Se presentan tres casos de infección atípica por Bartonella henselae en las que se evidenció compromiso ocular, manifestado como una neurorretinitis. Esta revisión destaca la importancia de la búsqueda activa de complicaciones oculares en pacientes con compromiso sistémico por Bartonella henselae, implicando un cambio en el tratamiento y pronóstico de la enfermedad.

Abstract Bartonella henselae is cat scratch disease's etiological agent, which is considered an endemic infection in Chile. It typically presents as a self-limited regional lymphadenopathy and less frequently with systemic involvement and extranodal or atypical manifestations: hepatosplenic, ocular or musculoskeletal involvement, among others. We present three cases of atypical cat scratch disease with ocular compromise, as neurorretinitis. This review highlights the importance of the active search for ocular complications in patients with disseminated cat scratch disease, leading to possible change in treatment and prognosis of the disease.

Flapless implant surgery: A review of the literature and 3 case reports.

Since the 1970s, modern Implantology is based on a concept of surgery with flap elevation. Gradually, several clinical trials demonstrated that a mid-crestal incision gives similar success rates compared to those obtained using the classical protocol. However, over the past decade in medicine it has been established the concept of minimally invasive surgery, consisting in taking advantage of advancements experienced in diagnostic techniques and specific surgical instruments, to perform surgical procedures infringing as less damage as possible to the patient The present work aims to produce a thorough review of the literature published on the field of Implantology with flapless surgery, to determine the current scientific evidence of the technique, along with illustrating the results with different clinical cases. After presenting the clinical cases, and the review of literature, we can say that flapless surgeries should be restricted to well-selected cases in which a proper clinical and radiological planning has been made. Patients treated with anticoagulant drugs or medically compromised equally can get benefitted by this minimal invasion technique. Key words:Flapless, minimally invasive surgery, dental implant.

Current Approaches of Bone Morphogenetic Proteins in Dentistry.

Bone morphogenic proteins (BMPs) are a group of osteoinductive proteins obtained from nonmineralized bone matrix; they are capable of stimulating the differentiation of pluripotent mesenchymal cells to osteoprogenitor cells. They have become a likely treatment option, given their action on regeneration and remodeling of bone lesions and increasing the bone response around alloplastic materials. It may be feasible in the near future for BMPs to replace autologous and allogenic bone grafts. The application of specific growth factors for osteoinduction without using a bone graft constitutes a real impact on bone regeneration. The use of BMP is not only focused on osteogenic regeneration: There are a variety of studies investigating other properties, such as periodontal or dental regeneration from the conservative viewpoint. In this review, we will highlight the role of the BMP in bone, periodontal and dental regeneration.