Uso de PCR digital para definir terapéuticas específicas y seguimiento en enfermedades autoinflamatorias / Use of digital PCR to define specific therapeutics and follow-up in autoinflammatory diseases

Las enfermedades autoinflamatorias (AIDs) son un grupo heterogéneo de desórdenes monogénicos o poligénicos, con características de disregulación inmune innata y/o adaptativa, cuyo mecanismo central es la autoinflamación pero también pueden presentarse con autoinmunidad e inmunodeficiencia. En estos últimos años el desarrollo de las tecnologías de secuenciación masiva han provocado una explosión en el descubrimiento de nuevos genes responsables de AIDs monogénicas. Esto remarca la importancia de implementar este tipo de estudios para llegar a un diagnóstico definitivo sobre todo en este grupo de patologías genéticamente muy diversas donde los fenotipos clínicos se solapan. Sin embargo, dada la presencia de variantes de significación incierta (VUS), los resultados pueden no ser concluyentes planteándose la necesidad de desarrollar pruebas funcionales para determinar la patogenicidad de dichas variantes genéticas. En nuestro grupo de trabajo estamos aplicando la PCR digital en gotas (ddPCR), una técnica cuantitativa de 3era generación altamente sensible, especifica y reproducible que no necesita de curvas de calibración, para desarrollar pruebas funcionales que permitan no sólo reclasificar variantes VUS para lograr diagnósticos definitivos sino también estudiar los mecanismos responsables de las principales AIDs que permitan una estratificación de las terapéuticas especificas a aplicar y de esta manera poder contribuir al diagnóstico, tratamiento y seguimiento de nuestros pacientes en forma personalizada. (AU)

Autoinflammatory diseases (AIDs) are a heterogeneous group of monogenic or polygenic disorders, with characteristics of inborn and/or adaptive immune dysregulation, whose central mechanism is autoinflammation but may also present with autoimmunity and immunodeficiency. In recent years the development of massive sequencing technologies has led to an exponential increase in the discovery of new genes responsible for monogenic AIDs. This emphasizes the importance of the implementation of this type of studies to make a definitive diagnosis, especially in this group of genetically very diverse diseases with overlapping clinical phenotypes. However, given the presence of variants of uncertain significance (VUS), the results may not be conclusive, raising the need to develop functional tests to determine the pathogenicity of these genetic variants. In our working group we are applying droplet digital PCR (ddPCR), a highly sensitive, specific and reproducible third generation quantitative technique that does not require calibration curves, to develop functional tests that allow not only to reclassify VUS variants to achieve definitive diagnoses but also to study the mechanisms responsible for the main AIDs that allow for the stratification of specific treatments to be used and thereby contribute to the individualized diagnosis, treatment, and follow-up of our patients (AU)

Perfil dos casos de câncer de mama entre acometidos no acre período de 2015 a 2019 ­ um estudo transversal / Profile of breast cancer cases between affected in acre period from 2015 to 2019 - a cross-sectional study / Perfil de los casos de cáncer de mama entre las personas afectadas en el período acre de 2015 a 2019 - un estudio transversal

Este estudo teve como objetivo analisar o perfil dos casos de câncer de mama no estado do Acre no período de 2015 a 2019. Trata-se de um estudo quantitativo com delineamento transversal. A amostra foi constituída por todos os casos de câncer de mama registrados no Acre e inseridos no Departamento de Informática do Sistema Único de Saúde (DATASUS) no período de 2015 a 2019. Foram identificados no período 293 casos da doença, com maior número de casos registrados no ano de 2019 (25,0%), sendo a maioria do sexo feminino (98,0%), na faixa etária de 40 a 49 anos (29,0%). O tempo decorrido desde o diagnóstico até o início do tratamento foi de mais de 60 dias (51,0%). A modalidade terapêutica mais utilizada foi a quimioterapia (55,0%). O local da realização do tratamento ocorreu capital do estado Rio Branco (80,0%). A maior parte dos acometidos, ainda encontra-se em tratamento (56,0%), no entanto (44,0%) evoluiu para óbito. O aumento da doença com o passar dos anos é notável no Acre. É importante destacar que ações voltadas para a prevenção e controle do câncer de mama continuam sendo fundamentais para auxiliar na diminuição do número de casos, como o rastreamento e diagnóstico precoce.

This study aimed to analyze the profile of breast cancer cases in the state of Acre in the period from 2015 to 2019. This is a quantitative study with a cross-sectional design. The sample consisted of all breast cancer cases registered in Acre and inserted in the Informatics Department of the Unified Health System (DATASUS) in the period from 2015 to 2019. In the period 293 cases of the disease were identified, with a greater number of cases registered in 2019 (25.0%), with the majority being female (98.0%), aged 40 to 49 years (29.0%). The time elapsed from diagnosis to the start of treatment was more than 60 days (51.0%). The most used therapeutic modality was chemotherapy (55.0%). The place where the treatment was performed took place in the state of Rio Branco (80.0%). Most of the people affected are still under treatment (56.0%), however (44.0%) died. The increase in the disease over the years is notable in Acre. It is important to highlight that actions aimed at the prevention and control of breast cancer continue to be fundamental to assist in reducing the number of cases, such as screening and early diagnosis.

Este estudio tuvo como objetivo analizar el perfil de los casos de cáncer de mama en el estado de Acre en el período de 2015 a 2019. Se trata de un estudio cuantitativo con diseño transversal. La muestra consistió en todos los casos de cáncer de mama registrados en Acre e ingresados en el Departamento de Informática del Sistema Único de Salud (DATASUS) en el período de 2015 a 2019. En el periodo se identificaron 293 casos de la enfermedad, siendo el mayor número de casos registrados en 2019 (25,0%), siendo la mayoría mujeres (98,0%), en el grupo de edad de 40 a 49 años (29,0%). El tiempo transcurrido desde el diagnóstico hasta el inicio del tratamiento fue superior a 60 días (51,0%). La modalidad terapéutica más utilizada fue la quimioterapia (55,0%). El lugar donde se realizó el tratamiento fue Rio Branco, la capital del estado (80,0%). La mayoría de los pacientes afectados siguen en tratamiento (56,0%), sin embargo, (44,0%) fallecieron. El aumento de la enfermedad a lo largo de los años es notable en Acre. Es importante destacar que las acciones dirigidas a la prevención y control del cáncer de mama siguen siendo fundamentales para ayudar a reducir el número de casos, como el cribado y el diagnóstico precoz.

Recensión. El modelo PLISSIT: una propuesta de esquema conceptual para el tratamiento conductual de los problemas sexuales / Critical review. The PLISSIT model: a proposed conceptual scheme for the behavioral treatment of sexual problems

El artículo muestra una guía orientada a profesionales de la salud cuyo objetivo es ordenar los problemas sexuales y dar herramientas sobre cómo abordar los mismos a través de la teoría del aprendizaje. El modelo conceptual de Annon ha posibilitado un mejor manejo de la situación a la hora de implementar un abordaje en la esfera sexual por parte de los profesionales, y a través de esta recensión se discute su uso pertinente en la actualidad. (AU)

The article shows a guide aimed at health professionals whose objective is to order sexual problems and provide tools on how to address them through learning theory. Annon’s conceptual model has made possible a better management when implementing a sexual oriented approach by professionals, so through this critical review, its pertinent use nowadays is discussed. (AU)

A network pharmacology approach to assess Reno-protective and -curative effects of methanolic extract of Malva neglecta Wallr in gentamicin induced renal toxicity rat model

Abstract The aim of present study was to explore protective and curative effects of Malve neglecta on kidneys. In silco study with network pharmacology was performed to find out potential target organs, genes and cellular cell lines which confirmed kidneys as target organ of phyto-constituents present in Malva neglecta extract. Gentamicin (40 mg/kg, i.p) was given to induce renal toxicity. Prophylactic study was performed with 300-, 600- and 900 mg/kg doses to find out nephro-protective and -curative effects and curative potential was evaluated at 900 mg/kg dose. Renal function biomarkers, blood urea, BUN, serum creatinine and uric acid, and oxidative stress measuring biomarkers, SOD, CAT, GSH and MDA levels in kidney homogenate were quantified at the end of study. Treatment groups showed decrease in blood urea, BUN, serum creatinine and uric acid levels dose dependently and curative group also showed decline in these biomarkers. SOD, CAT, GSH levels were increased and MDA level decreased in treatment groups significantly as compared to toxic control which revealed the role of oxidative stress in renal damage and anti-oxidant power of MN. Data suggested that use of MN along with drugs causing renal toxicity may prove beneficial due to its nephro- protective and curative effects.

Effects of low-level laser therapy on liver regeneration and laser parameters employed / Efeitos da laserterapia de baixa potência na regeneração hepática e parâmetros empregados de laser

Low-level laser therapy has several biological effects; one of them is tissue regeneration. Recent studies have been held on the application of laser therapy on the liver of rats after partial hepatectomy to promote liver regeneration. The aim of this article was to review the recent studies on the effects of low-level laser therapy on rat liver regeneration after partial hepatectomy and the laser parameters used in those studies. A review of recent relevant literature was performed in Pubmed, Scielo, Medline, and Bireme databases. Articles related to the application of low-level laser therapy on hepatic regeneration were included. Articles with hepatic regeneration in the presence of pathologies were not included. Nine studies were found matching the study criteria. In most studies, low-level laser therapy promoted liver regeneration after partial hepatectomy, without further damage to the remaining liver. Not all laser parameters required for the reproducibility of the study were described by all authors. The therapeutic use of low-level laser therapy in liver regeneration can be promising; however, since the liver is a vital organ, and the laser application is intraoperative, future studies are necessary. The parameters used must be properly described and standardized to allow the reproducibility of the study, in order to define a therapeutic window and thus, consider its clinical use. It is also essential to clarify the mechanisms by which laser promotes liver regeneration to guarantee its safety and therapeutic efficacy.

Laserterapia de baixa potência tem vários efeitos biológicos, sendo um deles a regeneração de tecido. Sua aplicação no fígado de ratos após hepatectomia parcial para promoção de regeneração hepática tem sido estudada recentemente. O objetivo deste artigo foi revisar os estudos recentes dos efeitos da laserterapia de baixa potência na regeneração de fígado de ratos após hepatectomia parcial de fígado e os parâmetros de laser empregados. Uma revisão da literatura relevante recente foi realizada nas bases de dados Pubmed, Scielo, Medline e Bireme. Artigos sobre a aplicação da laserterapia de baixa potência na regeneração de fígado foram incluídos. Artigos sobre regeneração hepática na presença de patologias foram excluídos. Nove estudos foram encontrados correspondendo aos critérios do estudo. Na maioria dos estudos, a laserterapia de baixa potência promoveu regeneração hepática após hepatectomia parcial, sem causar danos adicionais ao fígado remanescente. Não foram descritos todos os parâmetros necessários para reprodutibilidade dos estudos por todos os autores. O uso terapêutico da laserterapia de baixa potência na regeneração de fígado pode ser promissor, entretanto, como o fígado é um órgão vital e a aplicação do laser é intraoperativa, estudos futuros são necessários, assim como os parâmetros da aplicação de laser precisam ser descritos apropriadamente e padronizados, para permitir a reprodutibilidade do estudo, para que uma janela terapêutica possa ser definida e seu uso clínico possa ser considerado. Também é essencial esclarecer através de quais mecanismos o laser promove regeneração de fígado para garantir sua segurança e eficácia terapêutica.

Representaciones de niños y niñas de 8 a 12 años sobre el tratamiento virtual de psicopedagogía durante el contexto de pandemia 2020-2021: Cesac N°15 y Hospital Durand / Representations of children aged 8 to 12 on the virtual treatment of psychopedagogy during the context of pandemic 2020-2021: Cesac N°15 and Hospital Durand

La presente investigación pretende abordar una temática actual surgida en el contexto de pandemia por COVID19 bajo las regulaciones nacionales en relación al aislamiento preventivo y obligatorio vivenciado a lo largo del año 2020. En la misma se indaga sobre las representaciones de los niños y niñas en relación a los tratamientos psicopedagógicos virtuales, entendidos estos como un vínculo estable prolongado en un cierto tiempo entre un niño/a o adolescente (NNA) y un/una profesional de la psicopedagogía con el fin de acompañar o ayudar a disminuir su malestar en torno al aprendizaje en alguna de sus aristas. Estos encuentros desde el inicio de la pandemia se vieron enmarcados en aplicaciones digitales - como zoom o videollamada de Whatsapp debido al contexto de emergencia sanitaria mundial. El objetivo fundamental será investigar las características particulares del tratamiento psicopedagógico bajo la modalidad virtual a partir de las voces de los niños y las niñas que presentan dificultades en sus procesos de aprendizaje, es decir teniendo como eje central a los actores principales del espacio de tratamiento y sus representaciones sobre el mismo. (AU)

Investigación 2019-2020: Razones prevalentes de la asistencia regular al tratamiento psicopedagógico y grado de satisfacción con el mismo, en el Área Programática del Hospital Gral. de Agudos Dr. J. M. Ramos Mejía: ¿Por qué sostienen los que sostienen?" / Research 2019-2020: Prevalent reasons for the regular attendance to the psychopedagogical treatment and degree of satisfaction, in the Programmatic Area of the Hospital Gral. Dr. J. M. Ramos Mejía: Why do you hold those who hold?

Investigación del equipo de psicopedagogas residentes del Área Programática del Hospital Ramos Mejía (HRM), de la Ciudad de Buenos Aires, donde la clínica psicopedagógica es una de las principales tareas que desempeña, destinada a una población de niños/as entre 4 y 11 años. Desde 2019, se distribuye la encuesta de seguimiento por tratamiento sostenido, instrumento que se administró a los referentes de los niños/as que habían podido sostener el tratamiento. Considerando la multiplicidad de factores que pudieran afectar la asistencia regular, dicha encuesta incluye preguntas que indagan el motivo de llegada al equipo, la presencia de preocupaciones al iniciar el proceso, el tiempo de tratamiento, las razones explicitadas por las que se sostiene el espacio, la conveniencia del turno en cuanto día y horario, el tiempo de traslado al Área Programática, la calidad de la comunicación con la psicopedagoga del niño/a, entre otras. En el presente trabajo, a partir de la información antes mencionada, se procura analizar las razones prevalentes para el sostenimiento de los tratamientos psicopedagógicos en la población del área y su grado de satisfacción con el mismo.

Skin-Mountable Biosensors and Therapeutics: A Review.

Miniaturization of electronic components and advances in flexible and stretchable materials have stimulated the development of wearable health care systems that can reflect and monitor personal health status by health care professionals. New skin-mountable devices that offer seamless contact onto the human skin, even under large deformations by natural motions of the wearer, provide a route for both high-fidelity monitoring and patient-controlled therapy. This article provides an overview of several important aspects of skin-mountable devices and their applications in many medical settings and clinical practices. We comprehensively describe various transdermal sensors and therapeutic systems that are capable of detecting physical, electrophysiological, and electrochemical responses and/or providing electrical and thermal therapies and drug delivery services, and we discuss the current challenges, opportunities, and future perspectives in the field. Finally, we present ways to protect the embedded electronic components of skin-mountable devices from the environment by use of mechanically soft packaging materials.

Evaluation of the IncoStress device for urinary incontinence: a feasibility study and pilot randomised controlled trial.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to assess the feasibility of recruitment to and outcomes from a pilot randomised study of the IncoStress device as an adjunct to conservative treatment for urinary incontinence. METHODS: Women with urinary incontinence were randomised on a 2:1 basis to usual care (control) or usual care plus use of the IncoStress device (intervention). Process outcomes (retention and compliance) were recorded plus symptom outcomes (IQOL and ICIQ-FLUTS questionnaires). A sample of participants took part in an interview to understand the frequency of use of the device and satisfaction. RESULTS: Eighty women (51 intervention, 29 control) were recruited. Follow-up responses were obtained from 34 intervention group (66.7%) and 17 (58.6%) control patients. Women used the device for a median 3 days a week (0-7), 18 out of 34 (53%) found it easy to use and 21 (61.8%) were satisfied with the device. Median IQOL score in the intervention group improved from a baseline of 42.4 (0-94) to 68.2 (5-98) at follow-up and in the control group from 45.5 (0-88) to 53.0 (0-94). Median ICIQ-FLUTS score in the intervention group improved from 14.5 (6-35) to 12.5 (4-26) and in the control group from 15.0 (5-35) to 14.0 (6-38). CONCLUSIONS: Recruitment and randomisation were feasible and robust. This study demonstrates that a large-scale RCT is feasible and the IncoStress has potential value.

The Effect of Medical Technology Innovations on Patient Outcomes, 1990-2015: Results of a Physician Survey.

BACKGROUND: Developments in diagnostics, medical devices, procedures, and prescription drugs have increased life expectancy and quality of life after diagnosis for many diseases. Previous research has shown that, overall, increased investment in medical technology has led to increased health outcomes. In addition, the value of investment in specific innovations, particularly in new pharmaceuticals or biopharmaceuticals, has frequently been shown through an evaluation of the associated health outcomes and costs. Value assessments for all medical technologies and interventions are an important consideration in current debates on access and affordability of health care in the United States. OBJECTIVE: To identify practicing physician impressions of the historical effect of postdiagnosis innovations in medical technology on patient outcomes within the 8 health conditions that have the largest effect on health in the United States. METHODS: National statistics were used to identify the 8 conditions responsible for the most mortality and morbidity within the United States between 1990 and 2014. A physician survey was developed for each major condition to obtain physician opinion on the extent to which pharmaceuticals and biopharmaceuticals, medical devices, diagnostics, and surgical procedures contributed to improvements in postdiagnosis mortality and morbidity outcomes over the evaluated period. Respondents were provided with a fifth category, "cannot allocate," to account for postdiagnosis outcome gains resulting from other factors such as public health interventions. RESULTS: The conditions identified as having the greatest effect on morbidity and mortality since 1990 were breast cancer, ischemic heart disease, human immunodeficiency virus infection, diabetes, unipolar depression, chronic obstructive pulmonary disease, cerebrovascular disease, and lung cancer. After excluding other factors, physicians specializing in these conditions, with a mean of 21.4 years in practice, considered pharmaceuticals and biopharmaceuticals as having the greatest postdiagnosis effect across all 8 conditions, with 56% of outcome gains attributed to this innovation category. Diagnostics was the second biggest contributor at 20%. CONCLUSIONS: Physician perceptions indicated that attention should be paid to value assessments of innovative diagnostics, devices, and surgical procedures, as well as to pharmaceuticals and biopharmaceuticals, before goals for allocating health care expenditures among the different innovations are determined. DISCLOSURES: Funding for this study was provided by the National Pharmaceutical Council, a health policy research group that receives its funding from biopharmaceutical manufacturers. Wamble is employed by RTI Health Solutions, which received funding from the National Pharmaceutical Council to conduct this research. Ciarametaro and Dubois are employed by the National Pharmaceutical Council.

Facial asymmetry correction with moulded helmet therapy in infants with deformational skull base plagiocephaly.

PURPOSE: The recommendation issued by the American Academy of Pediatrics in the early 1990s to position infants on their back during sleep to prevent sudden infant death syndrome (SIDS) has dramatically reduced the number of deaths due to SIDS but has also markedly increased the prevalence of positional skull deformation in infants. Deformation of the base of the skull occurs predominantly in very severe deformational plagiocephaly and is accompanied by facial asymmetry, as well as an altered ear position, called ear shift. Moulded helmet therapy has become an accepted treatment strategy for infants with deformational plagiocephaly. The aim of this study was to determine whether facial asymmetry could be corrected by moulded helmet therapy. MATERIALS AND METHODS: In this retrospective, single-centre study, we analysed facial asymmetry of 71 infants with severe deformational plagiocephaly with or without deformational brachycephaly who were undergoing moulded helmet therapy between 2009 and 2013. Computer-assisted, three-dimensional, soft-tissue photographic scanning was used to record the head shape before and after moulded helmet therapy. The distance between two landmarks in the midline of the face (i.e., root of the nose and nasal septum) and the right and left tragus were measured on computer-generated indirect and objective 3D photogrammetry images. A quotient was calculated between the two right- and left-sided distances to the midline. Quotients were compared before and after moulded helmet therapy. Infants without any therapy served as a control group. RESULTS: The median age of the infants before onset of moulded helmet therapy was 5 months (range 3-16 months). The median duration of moulded helmet therapy was 5 months (range 1-16 months). Comparison of the pre- and post-treatment quotients of the left vs. right distances measured between the tragus and root of the nose (n = 71) and nasal septum (n = 71) revealed a significant reduction of the asymmetry (Tragus-Nasion-Line Quotient: 0.045-0.022; p < 0.0001; Tragus-Subnasale-Line Quotient: 0.045-0.021; p < 0.0001). The control group without treatment showed no significant change in the quotient (Tragus-Nasion-Line Quotient no helmet: 0.049-0.055/Tragus-Subnasale-Line Quotient no helmet: 0.039-0.055). CONCLUSION: Moulded helmet therapy can correct facial symmetry in infants with deformational plagiocephaly and associated facial and basal skull asymmetry.

Intravenous immunoglobulin therapy among pediatric patients: labeled and off-labeled indications

ABSTRACT This study was designed to evaluate utilization patterns and clinical outcome of intravenous immunoglobulin (IVIG) therapy among pediatric patients in a tertiary hospital. Demographic data, IVIG prescribed, and clinical outcome were retrospectively reviewed from the pharmacy dispensing data and patient medical records between 2007 and 2014. One hundred and fifteen instances of IVIG administration to 108 pediatric patients were recorded. A total of 61 cases (53%) and 54 cases (47%) of the IVIG administered were for labeled and off-labeled indications, respectively. Age, weight, specialty, total IVIG usage, length of hospital stays, and mortality rate were found to be significantly associated with the indication being labeled or off-labeled (p<0.05). However, there was no significant difference in terms of adverse reactions between labeled and off-labeled indications (p>0.05). Guidelines should be developed and implemented for rational and evidence-based use of IVIG to avoid unnecessary wastage.

Avaliação de terapias imunossupressoras em transplantes renais com uma abordagem metabolômica / Assessment of immunosuppressive therapies with a metabolomic approach

O aprimoramento das técnicas analíticas viabilizou a metabolômica, uma área da ciência que busca compreender, de forma comparativa, os metabólitos envolvidos nas vias bioquímicas. A metabolômica está inserida no contexto das "ômicas", que teve início na "Era Genômica", a qual permitiu a identificação de diversos genes. Em seguida, o interesse dos pesquisadores centrou no estudo dos metabólitos (metabolômica) mostrando ser uma ferramenta valiosa na pesquisa do transplante renal, que exige um tratamento medicamentoso por meio de imunossupressores. A combinação destes imunossupressores pode minimizar a rejeição do órgão transplantado, reforçando a necessidade de um estudo metabolômico, a fim de avaliar e comparar as mudanças ocorridas após o transplante em nível molecular, melhorando o conhecimento sobre a influência destes regimes e dando subsídios sobre prognósticos possíveis na área de transplante renal. Nesta tese foram avaliadas 2 terapias: Everolimo/ Prednisona/Tacrolimo (grupo 1) e Micofenolato mofetil/Prednisona/Tacrolimo (grupo 2) a partir de uma abordagem untargeted. No presente trabalho foram coletadas amostras de urina de pacientes ao longo de 6 meses. Foi necessário determinar a melhor condição para análise das amostras de urina dos pacientes. Desta forma, foram realizados estudos sobre alguns parâmetros que impactam no preparo de amostra abordando a influência da urease, tipos e proporção de solventes para precipitação de proteína, seleção do melhor agente derivatizante e tratamento de dados. A avaliação da medida de qualidade dos tratamentos com urease foi feita a partir do desvio padrão relativo (RSD) dos valores de intensidade de pico. A concentração de 10 mg mL-1 apresentou o melhor resultado. O estudo mostrou também que o teor de ureia na urina pode influenciar na identificação dos compostos. O número de compostos identificados foi menor quando a urina não foi tratada com urease, com aproximadamente 10 compostos a menos em relação à amostra tratada com a enzima, na mesma concentração de ureia adicionada. Dos solventes orgânicos testados para precipitação de proteínas nas amostras de urina, o isopropanol mostrou ser o solvente mais adequado na proporção 1:6 urina:solvente (v/v), utilizando-se 100 µL de urina. Foram testados dois protocolos de derivatização para análises por GC-MS: metoximação e sililação utilizando BSTFA e cloroformiato de metila. A comparação mostrou que o procedimento por BSTFA, com 40 metabólitos identificados, foi superior ao cloroformiato de metila, com 13 compostos identificados. No tratamento de dados com o software XCMS, os seguintes parâmetros foram avaliados: largura a meia altura do pico (fwhm), largura da banda (bw) e threshold (sntresh). Para avaliar a melhor combinação destes parâmetros, foi feita uma variação univariada destes valores. A qualidade do resultado de cada combinação foi monitorada pelos valores gerados de número de missing values, quantidade de picos com RSD <15% e número de valores duplicados. Os valores ótimos foram obtidos para a combinação: fwhm=4, bw=2 e threshold=5. A abordagem do estudo dos dois grupos de pacientes baseou-se inicialmente na comparação entre o dia 7 da terapia com os demais períodos (dia 14, mês 1, mês 3 e mês 6) e posteriormente avaliou-se a evolução temporal. A partir do mês 3 os valores de correlação e predição dos modelos de PLS-DA são melhores e já é eficaz na diferenciação entre os dois grupos. Foram observadas perturbações no metabolismo de carboidratos em ambos os grupos, como açúcares, glicerol e N-acetil-D-manosamina. No grupo 1, foram observados metabólitos discriminantes da classe dos poliois e das vias do ciclo do ácido cítrico e degradação de xenobióticos, enquanto que, no grupo 2, foi observada alteração do hidroxibutirato, um corpo cetônico. Neste grupo, foi observado também um aumento do ácido hipúrico, ácido acetamido butírico, ácido benzoico, entre outros. Nesta tese foi possível demonstrar que a metabolômica é uma ferramenta importante para comparar metabólitos discriminantes entre dois regimes imunossupressores, sendo um estudo piloto que visa fornecer subsídios para avaliação da influência destas terapias no prognóstico de transplante renal

The improvement of analytical techniques enabled the emergence of metabolomics, which aims to compare the metabolites involved in biochemical pathways, in certain biological conditions. Metabolomics is inserted in the "omics" context, which began in the "Genomic Age", and allowed the identification of several genes. After that, the researchers focused on the study of metabolites. Among several applications, metabolomics can be a valuable tool in renal transplant research, which requires a drug treatment through immunosuppressants. The combination of these immunosuppressants can minimize toxicity and rejection of the transplanted organ, reinforcing the need for a metabolomic study, in order to evaluate and compare changes after transplantation at the molecular level, improving knowledge about the influence of these regimens and giving subsidies on prognosis in the area of renal transplantation. In this thesis two immunosuppressive therapies were evaluated by an untargeted approach: Everolimus/Prednisone/Tacrolimus (group 1) and Mycophenolate mofetil/Prednisone/Tacrolimus (group 2). In this study, urine samples were collected from patients over 6 months. It was necessary to determine the best condition for analysis of patients' urine samples. Thus, studies were carried out on some parameters that impact on sample preparation, evaluating the influence of urease, types and proportion of solvents for protein precipitation, selection of the best derivatizing agent, and data treatment. The evaluation of the quality measure of the urease treatments was made from the relative standard deviation (RSD) of the peak intensity values. The concentration of 10 mg mL-1 presented the best result. The study also showed that urine urea content may influence the identification of the compounds. The number of identified compounds was lower when urine was not treated with urease, with approximately 10 compounds less than the enzyme-treated sample, at the same concentration of urea added. In the evaluation of the organic solvents tested for protein precipitation in the urine samples, isopropanol was the most suitable solvent in the ratio 1: 6 urine:solvent (v/v), using 100 µL of urine. Two derivatization protocols were tested for GC-MS analysis: metoximation and silylation with BSTFA and methyl chloroformate. The comparison between the two derivatization protocols showed that the BSTFA procedure, with 40 identified metabolites, was superior to methyl chloroformate with 13 compounds identified. In data processing with the XCMS software, the following parameters were evaluated: full width at half maximum of the peak (fwhm), bandwidth (bw) and threshold (sntresh). To evaluate the best combination of these parameters, a univariate variation of these values was made. The quality of the result of each combination was monitored by the number of missing values, number of peaks with RSD <15%, and number of duplicate values. The optimal values were obtained for the combination: fwhm=4, bw=2 and threshold =5. The study of the two groups of patients was initially based on the comparison between day 7 of the therapy with the other periods (day 14, month 1, month 3 and month 6) and later the temporal evolution was evaluated. From month 3 the values of correlation and prediction of the PLS-DA models are better and already effective in the differentiation between the two groups. Disorders in carbohydrate metabolism were observed in both groups with sugars and glycerol and N-acetyl-D-mannosamine as discriminant metabolites. In group 1, discriminant metabolites of the class of polyols and citric acid cycle pathways and degradation of xenobiotics were observed, and in group 2 alteration of hydroxybutyrate, a ketone body, was observed. In this group an increase of hippuric acid, acetamido butyric acid, benzoic acid, among others, was also observed. In this thesis it was possible to demonstrate that metabolomics is an important tool to compare discriminant metabolites between two immunosuppressive regimens, being a pilot study that aims to provide future subsidies to evaluate the influence of these therapies on the renal transplant prognosis

Opciones terapéuticas de las varices / Therapeutic options for varicose veins

No disponible

Vigencia de la endarterectomía carotídea para el tratamiento de estenosis asintomática en la era de las estatinas / Effectiveness of carotid endarterectomy for asymptomatic carotid stenosis in the statins era

El beneficio de la endarterectomía carotídea en pacientes asintomáticos es actualmente cuestionado por la reducción observada en la tasa de infarto cerebral con tratamiento médico actual. Se realiza una revisión de la evidencia disponible. El uso perioperatorio de estatinas, mejor estandarización de técnica quirúrgica, concentración de endarterectomías en cirujanos de mayor volumen quirúrgico e identificación de pacientes de mayor riesgo han permitido una disminución paralela de los infartos postendarterectomía. Se ha identificado una subpoblación asintomática con mayor riesgo de desarrollar eventos neurológicos: estenosis carotídeas severas, rápida progresión de estenosis, presencia de infartos hemisféricos silentes, microembolias en doppler transcraneal, menor reserva cerebrovascular y placas inestables. El futuro de la endarterectomía carotídea radica en la identificación de lesiones de mayor riesgo de infarto y realizar cirugía con mínima morbimortalidad. Los estudios de imágenes han mostrado un rápido avance, pero se requiere de mejor validación antes de cambiar las guías de manejo vigentes

The benefit of carotid endarterectomy in asymptomatic patients is currently questioned, due to an observed reduction in stroke rate with current medical treatment. A review is carried out on the available evidence. The perioperative use of statins, better standardisation of surgical techniques, concentration of endarterectomy by surgeons with a higher surgical volume, and identification of high-risk patients, have led to a parallel decrease in post-endarterectomy stroke. An asymptomatic subpopulation has been identified with an increased risk of developing neurological events: severe carotid stenosis, rapid progression of stenosis, presence of silent hemispherical infarcts, micro-emboli in transcranial doppler, lower cerebrovascular reserve, and unstable plaques. The future of carotid endarterectomy in asymptomatic patients lies in the identification of lesions with increased risk of stroke and performing surgery with minimal morbidity and mortality. Imaging studies have rapidly progress, but better validation is required before changing current management guidelines

Embolia aérea cerebral masiva tras colangiopancreatografía retrógrada endoscópica. Presentación de un caso y revisión de la bibliografía / Massive cerebral air embolism following endoscopic retrograde cholangiopancreatography. A case report and review of the literature

Introducción. La embolia aérea cerebral tras procesos endoscópicos es una complicación infrecuente, pero que puede tener consecuencias catastróficas. Caso clínico. Varón de 85 años, diagnosticado de colangiocarcinoma distal con criterios de irresecabilidad, al cual se coloca una prótesis biliar de drenaje. Se realiza una colangiopancreatografía retrógrada endoscópica para el cambio de prótesis. Tras el procedimiento, el paciente sufre un deterioro de las constantes vitales y del nivel de consciencia, y requiere intubación orotraqueal. En la tomografía axial computarizada craneal se evidencia una embolia aérea masiva con focos de isquemia hiperaguda en ambos hemisferios. El paciente fallece posteriormente. Conclusiones. El embolismo aéreo cerebral tras una colangiopancreatografía retrógrada endoscópica es infrecuente, pero potencialmente letal. La manipulación de la pared biliointestinal en las exploraciones endoscópicas podría originar comunicaciones entre la luz y el sistema venoso. Esto, unido a la alta presión de insuflación para la realización de la prueba, condicionaría el paso de aire al sistema venoso portal y, de ahí, al sistema circulatorio. En el sistema nervioso central, las burbujas de aire provocarían una obstrucción vascular, con la consiguiente isquemia y necrosis del tejido. Es fundamental un diagnóstico precoz y una terapia de soporte vital. Su rápido manejo puede contribuir a un mejor pronóstico, que en principio es sombrío (AU)

Introduction. Cerebral air embolism following endoscopic processes is an infrequent complication, but can have catastrophic consequences. Case report. An 85-year-old male diagnosed with distal cholangiocarcinoma with criteria for unresectability who was submitted to placement of a biliary drainage prosthesis. Endoscopic retrograde cholangiopancreatography was performed to change the prosthesis. After the procedure, the patient’s vital signs and level of consciousness underwent a decline, and orotracheal intubation was required. A computerised axial tomography scan of the head showed evidence of a massive air embolism with focal points of hyperacute ischaemia in both hemispheres. The patient later died. Conclusions. Cerebral air embolism following endoscopic retrograde cholangiopancreatography is infrequent, but potentially lethal. Manipulation of the bilio-intestinal wall in endoscopic examinations could give rise to communications between the lumen and the venous system. This, together with the high insufflation pressure used to conduct this test, would condition the passage of air to the portal venous system, and from there to the circulatory system. In the central nervous system, air bubbles would lead to a vascular obstruction, with the subsequent ischaemia and necrosis of tissues. An early diagnosis and life support therapy are essential. Its timely management can contribute to a better prognosis which, at least initially, is gloomy (AU)

The measurement of intraocular pressure over positive soft contact lenses by rebound tonometry / Medición de la presión intraocular sobre lentes de contacto blandas positivas, mediante tonometría de rebote

Purpose: To investigate if the accuracy of intraocular pressure (IOP) measurements using rebound tonometry over disposable hydrogel (etafilcon A) contact lenses (CL) is affected by the positive power of the CLs. Methods: The experimental group comprised 26 subjects, (8 male, 18 female). IOP measurements were undertaken on the subjects’ right eyes in random order using a Rebound Tonometer (ICare). The CLs had powers of +2.00D and +6.00D. Measurements were taken over each contact lens and also before and after the CLs had been worn. Results: The IOP measure obtained with both CLs was significantly lower compared to the value without CLs (t test; p<0.001) but no significant difference was found between the two powers of CLs. Conclusions: Rebound tonometry over positive hydrogel CLs leads to a certain degree of IOP underestimation. This result did not change for the two positive lenses used in the experiment, despite their large difference in power and therefore in lens thickness. Optometrists should bear this in mind when measuring IOP with the rebound tonometer over plus power contact lenses (AU)

Objetivo: Investigar si la precisión de las mediciones de la presión intraocular (PIO), utilizando la tonometría de rebote sobre las lentes de contacto (LC) desechables de hidrogel (etafilcon A), se ve afectada por la potencia positiva de dichas lentes. Métodos: El grupo experimental incluyó a 26 sujetos, (8 varones, 18 mujeres). Se realizó la medición de la PIO en los ojos derechos de los sujetos, de modo aleatorio, utilizando un Tonómetro de Rebote (ICare). Las LC tenían potencias de +2,00D y +6,00D. Se realizaron mediciones con cada lente de contacto, y también antes y después a su uso. Resultados: El valor de la PIO obtenido con ambas LC fue considerablemente menor al valor sin LC (t del test; p<0,001), aunque no se halló una diferencia significativa entre las dos potencias de las lentes. Conclusiones: La tonometría de rebote sobre las LC positivas de hidrogel origina un cierto grado de subestimación del PIO. Este resultado no sufrió variación entre las dos lentes positivas utilizadas en el experimento, a pesar de la gran diferencia de potencia, y por tanto del espesor de las lentes. Los optometristas deberían de tener en cuenta estos resultados en a la hora de medir el PIO con un tonómetro de rebote, con lentes de contacto de mayor potencia (AU)

Sweet Syndrome: A Review and Update / Síndrome de Sweet: Revisión y puesta al día

Atypically presents in patients with pirexya, neutrophilia, painful tender erytomatous papules, nodules and plaques often distributed asymmetrically. Frequent sites include the face, neck and upper extremities. Affected sites show a characteristical neutrophilic infiltrate in the upper dermis. Its etiology remains elucidated, but it seems that can be mediated by a hypersensitivity reaction in which cytokines, followed by infiltration of neutrophils, may be involved. Systemic corticosteroids are the first-line of treatment in most cases. We present a concise review of the pathogenesis, classification, diagnosis and treatment update of this entity

El síndrome de Sweet es la entidad más representativa de las dermatosis neutrofílicas. Por lo general se presenta en pacientes con fiebre, neutrofilia, pápulas erytomatosas dolorosas, nódulos y placas. Los sitios frecuentemente afectados incluyen la cara, cuello y extremidades superiores los cuales característicamente presentan un infiltrado neutrofílico en la dermis superior. Su etiología no esta bien establecida, pero parece que puede estar mediada por una reacción de hipersensibilidad de las citocinas, seguido por un infiltrado de neutrófilos. Los corticosteroides sistémicos son la primera línea de tratamiento en la mayoría de los casos. Se presenta una revisión actual de la patogénesis, clasificación, diagnóstico y tratamiento de esta entidad