Salivary biomarkers: novel noninvasive tools to diagnose chronic inflammation / 国际口腔科学杂志·英文版

Several chronic disorders including type 2 diabetes (T2D), obesity, heart disease and cancer are preceded by a state of chronic low-grade inflammation. Biomarkers for the early assessment of chronic disorders encompass acute phase proteins (APP), cytokines and chemokines, pro-inflammatory enzymes, lipids and oxidative stress mediators. These substances enter saliva through the blood flow and, in some cases, there is a close relation between their salivary and serum concentration. Saliva can be easily collected and stored with non-invasive and cost-saving procedures, and it is emerging the concept to use it for the detection of inflammatory biomarkers. To this purpose, the present review aims to discuss the advantages and challenges of using standard and cutting-edge techniques to discover salivary biomarkers which may be used in diagnosis/therapy of several chronic diseases with inflammatory consequences with the pursuit to possibly replace conventional paths with detectable soluble mediators in saliva. Specifically, the review describes the procedures used for saliva collection, the standard approaches for the measurement of salivary biomarkers and the novel methodological strategies such as biosensors to improve the quality of care for chronically affected patients.

Delineating asthma according to inflammation phenotypes with a focus on paucigranulocytic asthma / 中华医学杂志(英文版)

Asthma is characterized by chronic airway inflammation and airway hyper-responsiveness. However, the differences in pathophysiology and phenotypic symptomology make a diagnosis of "asthma" too broad hindering individualized treatment. Four asthmatic inflammatory phenotypes have been identified based on inflammatory cell profiles in sputum: eosinophilic, neutrophilic, paucigranulocytic, and mixed-granulocytic. Paucigranulocytic asthma may be one of the most common phenotypes in stable asthmatic patients, yet it remains much less studied than the other inflammatory phenotypes. Understanding of paucigranulocytic asthma in terms of phenotypic discrimination, distribution, stability, surrogate biomarkers, underlying pathophysiology, clinical characteristics, and current therapies is fragmented, which impedes clinical management of patients. This review brings together existing knowledge and ongoing research about asthma phenotypes, with a focus on paucigranulocytic asthma, in order to present a comprehensive picture that may clarify specific inflammatory phenotypes and thus improve clinical diagnoses and disease management.

Parámetros del líquido amniótico para diagnóstico de respuesta inflamatoria en parto pretérmino / Amniotic fluid parameters for the diagnosis of inflammatory response in preterm delivery

OBJETIVO: Evaluar el rendimiento del Gram, la glucosa y los leucocitos en líquido amniótico para el diagnóstico de respuesta inflamatoria fetal y materna en pacientes con parto pretérmino. MÉTODO: Estudio de rendimiento de pruebas diagnósticas. Se incluyeron 63 pacientes a quienes se les realizó amniocentesis por sospecha de infección intraamniótica. Se estudió la placenta y se comparó con el Gram, la glucosa y el recuento de leucocitos en líquido amniótico para ver su relación con la respuesta inflamatoria. Se evaluaron la sensibilidad, la especificidad, las razones de verosimilitud (LR, likelihood ratio), los valores predictivos y el valor de kappa. RESULTADOS: Las pruebas con mejor rendimiento fueron en conjunto la glucosa 50/mm3 en líquido amniótico, con una especificidad del 94,3% (intervalo de confianza del 95% [IC95%]: 84,6-98,1), LR + 8,83 (IC95%: 2,5-31,2) y kappa de 0,48 (IC95%: 0,15-0,82). También se consideró la propuesta de un nuevo punto de corte para el recuento de leucocitos en líquido amniótico en la respuesta inflamatoria fetal. CONCLUSIONES: La combinación del recuento de leucocitos en líquido amniótico y los valores de glucosa mejora el rendimiento para el diagnóstico de respuesta inflamatoria fetal en comparación con la histopatología de la placenta, lo que proporciona información útil para el enfoque de los recién nacidos.

OBJECTIVE: To evaluate the performance of Gram, glucose and leukocytes in amniotic fluid for the diagnosis of fetal and maternal inflammatory response in patients with preterm delivery. METHOD: A diagnostic performance test study was carried out. Sixty-three patients with preterm labor were included who underwent amniocentesis due to suspected intra-amniotic infection. Histopathology of the placenta was studied and compared with the Gram result, glucose and leukocyte count in amniotic fluid, and their relationship with the maternal and fetal inflammatory response. Sensitivity, specificity, likelihood ratios, predictive values, and kappa were evaluated. RESULTS: The tests with the best performance were overall glucose 50/mm3 in amniotic fluid for the diagnosis of the fetal inflammatory response, with a specificity of 94.3% (95% confidence interval [95% CI]: 84.6-98.1%), likelihood positive ratio 8.83 (95% CI: 2.5-31.2) and kappa of 0.48 (95% CI: 0.15-0.82). A new cut-off point for leukocyte count in amniotic fluid to diagnose fetal inflammatory response was proposed. CONCLUSIONS: The combination of amniotic fluid leukocyte count and amniotic fluid glucose values improves performance for the diagnosis of inflammatory response compared with placental histopathology, providing useful information for newborns approach.

Estados depresivos en pacientes con enfermedades crónicas no transmisibles / Depressive States in Patients with Chronic Noncommunicable Diseases

Introducción: La relación entre las enfermedades crónicas no transmisibles y los trastornos mentales, como ansiedad y depresión, ocurren de modo bidireccional, es decir, que la presencia de una condición predispone el desarrollo de la otra. Objetivo: Indagar en la literatura revisada acerca de los aspectos relacionados con los estados depresivos en pacientes con enfermedades crónicas no transmisibles de mayor impacto en salud pública. Métodos: Investigación tipo documental por revisión bibliográfica sistemática de estudios sobre los estados depresivos y el padecimiento de enfermedades crónicas no transmisibles, publicados en revistas médicas de acceso abierto en español o inglés, que contribuyan a la comprensión del por qué la comorbilidad de estas enfermedades. Conclusiones: Un diagnóstico y control deficiente de las enfermedades crónicas no transmisibles y de los estados depresivos, pueden llevar a la falta de adherencia al tratamiento, lo que aumenta la morbimortalidad de las enfermedades crónicas no transmisibles. En los estados depresivos y las enfermedades crónicas no transmisibles se comparten mecanismos biológicos de actividad inmunológica que, en un complejo equilibrio, determinado por la activación de genes específicos, en conjunto contribuyen con la aparición de estados depresivos y agravamiento de las enfermedades crónicas no transmisibles. Es necesaria una visión integral a nivel diagnóstico y de control que permitan en conjunto decidir el tratamiento más adecuado según las características del paciente, para proceder con la derivación oportuna y apropiada en cada caso(AU)

Introduction: The relationship between chronic noncommunicable diseases and mental disorders, such as anxiety and depression, occur in a bidirectional way, that is, the presence of one condition predisposes the development of the other. Objective: To investigate, in the literature reviewed, about the aspects related to depressive states in patients with chronic noncommunicable diseases of major impact on public health. Methods: Documental research that consisted in the systematic literature review of studies about depressive states and being affected by chronic noncommunicable diseases, published in open access medical journals in Spanish or English and that contribute to the understanding the comorbidity of these conditions. Conclusions: Poor diagnosis and control of chronic noncommunicable diseases and depressive states can lead to lack of adherence to treatment, which increases the morbimortality of chronic noncommunicable diseases. Depressive states and chronic noncommunicable diseases share biological mechanisms of immune activity that, in a complex balance, determined by the activation of specific genes, together contribute to the onset of depressive states and aggravation of chronic noncommunicable diseases. It is necessary to have a comprehensive vision at the diagnostic and control levels that allows to decide together the most adequate treatment according to the patient's characteristics, in order to proceed with the opportune and appropriate referral in each case(AU)

Correlación de índice PO2/FiO2 con parámetros inflamatorios y de coagulación en pacientes críticos con covid-19. Lombardía, 2020 / PO2/FiO2 index correlation with inflammatory and coagulation parameters in critically-ill patients with COVID-19 in Lombardy, 2020

RESUMEN Introducción: el conocimiento de la fisiopatología de la enfermedad ha revolucionado el enfoque tradicional en el tratamiento de las enfermedades causadas por virus respiratorios. Actualmente, se utilizan marcadores de la respuesta inflamatoria para diagnosticar, estratificar y predecir en muchos casos el comportamiento futuro del enfermo de covid-19. Objetivo: caracterizar la naturaleza de la relación entre el índice PO2/FiO2 y los parámetros inflamatorios y de coagulación en pacientes graves por la covid-19, en la región de Lombardía, Italia. Materiales y métodos: se realizó un estudio analítico, longitudinal, retrospectivo con 191 pacientes graves y críticos, que ingresaron con diagnóstico de covid-19 del 1 de abril al 20 mayo de 2020, en el Hospital Mayor de Crema, en la región de Lombardía, Italia. Resultados: las correlaciones evidenciadas fueron las siguientes: proteína C reactiva (-0,417) p = 0; procalcitonina (-0,152) p = 0,018; dímero D (-0,112) p = 0,061; fibrinógeno (-0,272) p = 0,000; creatinina plasmática (-0,320) p = 0,000; conteo de linfocitos (0,028) p = 0,000; troponina (-0,028) p = 0,142, y lactato (-0,191) p = 0,288. Conclusiones: los marcadores inflamatorios en la patogenia de la enfermedad juegan un rol capital, y el enfoque hacia este renglón del tratamiento médico antiinflamatorio de cualquier tipo es mandatorio. Se debe realizar un correcto monitoreo de la coagulación, usar heparinas de bajo peso molecular, así como mantener un adecuado soporte hemodinámico capaz de evitar las disoxias celulares que progresen al fallo multiorgánico (AU).

ABSTRACT Introduction: the knowledge of disease physiopathology has revolutionized the traditional approach in the treatment of diseases caused by respiratory viruses. Currently, the markers of inflammatory answer are used to diagnose, stratify and predict in many cases the future behavior of COVID-19 patients. Objective: to characterize the nature of the relationship between PO2/FiO2 (PAFI, Spanish acronym of PA= presión arterial [arterial pressure], FI=fracción inspirada [inspired fraction]) and coagulation and inflammatory parameters in seriously-ill patients with COVID-19, in the region of Lombardy, Italy. Materials and methods: a retrospective, longitudinal, analytic study was carried out in 191 severe and critical patients who were admitted in Hospadale Maggiori di Crema, in the region of Lombardy, Italy, with the diagnosis of COVID-19, in the period April 1st-May 20, 2020. Results: the evidenced correlations were the following: reactive C protein (-0.417) p=0; procalcitonin (PCT) (-0.152) p=0.018. D dimer (-0.112) p=0.061; Fibrinogen (-0.272) p=0.000; Plasma creatinine (-0.320) p=0.000; lymphocytes count (0,028) p=0,000; troponin (-0.028) p=0.142; and lactate (-0.191) p=0.288. Conclusions: inflammatory markers play a capital role in the disease pathogenesis, and approaching this item of the medical anti-inflammatory treatment is mandatory. It is useful to keep a correct coagulation screening, using low molecular weight heparins, and also keeping an adequate hemodynamic support able to avoid cell dysoxia progressing to multiorgan failure (AU).

Síndromes mielodisplásicos y sistema inmunitario / Myelodysplastic Syndrome and Immune System

Introducción: Los síndromes mielodisplásicos constituyen un grupo heterogéneo de desórdenes hematológicos clonales adquiridos, que afectan la célula madre. Se caracterizan morfológicamente por: hematopoyesis ineficaz, citopenias periféricas progresivas, displasia en uno o más linajes celulares y tendencia evolutiva a leucemia aguda. Los avances recientes en la comprensión de los mecanismos genéticos y moleculares de los síndromes mielodisplásicos, han revelado la asociación entre alteraciones inmunológicas y las mutaciones recurrentes. Las células de la respuesta inmune innata y adaptativa, así como diversos mediadores solubles liberados por ellas, pueden establecer una respuesta antitumoral protectora o, por el contrario, inducir eventos de inflamación crónica que favorezcan la promoción y progresión de esta enfermedad. Objetivos: Resumir los conocimientos actuales de la relación sistema inmune-síndromes mielodisplásicos, enfatizando en las células inmunes del microambiente de la médula ósea y su importancia en la clínica de la enfermedad. Métodos: Se realizó investigación bibliográfica-documental acerca del tema. Se consultaron las bases de datos Scielo y Pubmed. Conclusiones: La comprensión de la función dual que ejerce el sistema inmune en los síndromes mielodisplásicos, constituye un desafío y son necesarios estudios clínicos rigurosos para poder establecer el valor de la manipulación del sistema inmune como una forma posible de tratamiento de esta enfermedad(AU)

Introduction: Myelodysplastic syndromes (MDS) constitute a heterogeneous group of acquired clonal hematological disorders that affect the stem cell. These are characterized morphologically and clinically by: ineffective hematopoiesis, progressive peripheral cytopenia, dysplasia in one or more cell lineages, in most of cases and evolutionary tendency to acute leukemia. Recent advances in understanding the genetic and molecular mechanisms of MDS have revealed the association between immunological alterations and recurrent mutations. Cells of the innate and adaptive immune response, as well as various soluble mediators released by them, can establish a protective antitumor response or, on the contrary, induce events of chronic inflammation that favor the promotion and progression of this disease. Objective: To summarize the current knowledge of the immune system-MDS relationship, emphasizing the immune cells of the bone marrow microenvironment and their importance in the clinic of the disease. Methods: A bibliographic-documentary research was carried out on the subject. The Scielo and Pubmed databases were consulted. Conclusions: Understanding the dual role of the immune system in MDS constitutes a challenge and rigorous clinical studies are necessary to establish the value of manipulating the immune system as a possible form of treatment of this disease(AU)

Migración de malla: una complicación temible / Mesh migration: a fearsome complication

RESUMEN La migración de malla en el posoperatorio alejado de la eventroplastìa y su consecuente infección es una complicación poco frecuente y peligrosa. La malla migrada genera reacción inflamatoria de tipo cuerpo extraño. Puede causar obstrucción intestinal, perforación intestinal o dolor abdominal cróni co. Solo se informan 4 casos en la literatura mundial de migración y uno con compromiso intestinal. Presentamos el caso de un tumor inflamatorio adherido a la pared abdominal, con contenido de poli propileno. El objetivo de esta carta científica es presentar una complicación poco habitual, destacando los aspectos más importantes de su manejo, definiendo algunas recomendaciones y remarcando la importancia del abordaje multidisciplinario.

ABSTRACT Mesh migration with subsequent infection years after incisional hernia repair is an uncommon and dangerous complication. Mesh migration produces an inflammatory foreign body reaction and can cause bowel obstruction, bowel perforation or chronic abdominal pain. Only four cases have been reported in the international literature, one of them with bowel involvement. We report a case of an inflammatory tumor containing polypropylene traces adhered to the abdominal wall. The aim of this scientific letter is to report a rare complication, emphasizing the most relevant aspects about its ma nagement, recommendations, and the relevance of a multidisciplinary approach.

Papel de la proteína C reactiva y la velocidad de sedimentación globular en la predicción de colecistectomía laparoscópica dificultosa: su aplicación en un programa de residencia universitario / Role of C-reactive protein and erythrocyte sedimentation rate to predict difficult laproscopic cholecystectomy in a university residency program

Antecedentes: la colecistectomía laparoscópica es uno de los procedimientos quirúrgicos más frecuentemente realizados. Las diferencias en la anatomía y en el grado de inflamación vesicular suelen causar dificultades técnicas intraoperatorias. Objetivo: determinar el valor de la proteína C reactiva (PCR) y la velocidad de sedimentación globular (VSG) como predictores de colecistectomía dificultosa y evaluar su aplicación en la planificación prequirúrgica de un programa de residencia universitario. Material y métodos: se confeccionó un estudio retrospectivo, analítico, en un hospital universitario de tercer nivel. Se incluyeron 104 pacientes adultos operados de colecistectomía laparoscópica por litiasis vesicular sintomática entre enero y julio de 2019. Se categorizó a los pacientes en un grupo de colecistectomías dificultosas y otro de colecistectomías no dificultosas. Resultados: se obtuvieron diferencias estadísticamente significativas al comparar los valores de VSG y PCR de ambos grupos (p < 0,001). La sensibilidad de la VSG fue del 100%, la especificidad del 45%, el VPP del 40% y el VPN de 100%. La sensibilidad de la PCR fue del 87,5%, la especificidad del 86,3%, el VPP del 70% y el VPN de 95%. Ambos parámetros se vieron elevados en 14 de 16 colecistectomías dificultosas y en 2 de 44 colecistectomías no dificultosas. La sensibilidad para ambos parámetros elevados fue del 87,5%, la especificidad del 95%, el VPP del 87,5% y el VPN de 95%. Conclusión: la VSG y la PCR han demostrado ser un método fiable en la predicción de colecistectomías dificultosas por litiasis vesicular sintomática. Esto podría ser aplicado en la programación de cirugías dentro de un programa de residencia universitario.

Background: laparoscopic cholecystectomy is one of the most common procedures performed in general surgery. The anatomical differences of the gallbladder and the presence of factors related to inflammation can cause technical issues during surgery. Objective: the aim of the present study was to determine the value of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as predictors of difficult cholecystectomy and to evaluate their application during presurgical planning within a university residency program. Material and methods: we conducted a retrospective and analytical study in a tertiary university hospital. A total of 104 adult patients undergoing laparoscopic cholecystectomy due to symptomatic cholelithiasis between January and July 2019 were included. The patients were categorized into two groups: difficult cholecystectomy and non-difficult cholecystectomy. Results: there were statistically significant differences in ESR and CRP values between both groups (p < 0.001). Sensitivity of ESR was 100%, specificity was 45%, with a PPV of 40% and NPV of 100%. Sensitivity of CRP was 87.5%, specificity was 86.3%, with a PPV of 70% and NPV of 95%. Both parameters were elevated in 14 of 16 difficult cholecystectomies and in 2 of 44 non-difficult cholecystectomies. Sensitivity of CRP was 87.5%, specificity was 86.3%, with a PPV of 70% and NPV of 95%. Conclusion: measuring ESR and CRP has proved to be a reliable method to predict difficult cholecystectomies due to symptomatic cholelithiasis. This could be applied for surgical planning within a university residency program.

Tumor miofibroblástico inflamatorio: presentación variable de una misma patología / Inflammatory myofibroblastic tumor: variable presentation of the same pathology

INTRODUCCIÓN: El tumor miofibroblástico inflamatorio (TMI) es una neoplasia benigna infrecuente, de comportamiento clínico impredecible. OBJETIVOS: describir 3 casos de TMI diagnosticados entre marzo 2014 y enero 2018 en Hospital Clinico San Borja Arriaran, y realizar una revisión actualizada de la literatura. CASO 1: Adolescente de género masculino de 14 años de edad, hospitalizado por dolor abdominal, diagnosticado de invaginación yeyunoyeyunal secundaria a un tumor de pared intestinal. La histología fue compatible con un tumor miofibroblástico inflamatorio. CASO 2: Adolescente de género femenino, edad 12 años, hospitalizada por neumonía y dolor lumbar en estudio asociado a pérdida de peso. Se diagnosticó una masa retroperitoneal que comprometía el músculo psoas derecho, músculos paravertebrales, vértebras, riñón derecho y diafragma ipsilateral. Se efectuó biopsia por punción cuyo resultado fue compatible con un tumor miofibroblástico inflamatorio. CASO 3: Preadolescente de género femenino de 11 años de edad, hospitalizada para estudio de infección del tracto urinario a repetición. Se identificó un tumor vesical y la biopsia mostró ser compatible con tumor miofibroblástico inflamatorio. CONCLUSIÓN: Debido al comportamiento variable del tumor miofibroblástico inflamatorio, el manejo de este dependerá de la localización, la expresión del anaplasic like lymphoma (ALK), el comportamiento del tumor y la posibilidad de resección.

INTRODUCTION: The inflammatory myofibroblastic tumor is an infrequent benign neoplasm with unpredictable cli nical behavior. OBJECTIVES: to describe three clinical cases at the San Borja Arriarán Clinical Hospital between March 2014 and January 2018 and to carry out an updated review of the literature. CASE 1: 14-year-old male adolescent, hospitalized due to abdominal pain, diagnosed with jejunojejunal intus susception secondary to an intestinal wall tumor. The histology was compatible with an inflamma tory myofibroblastic tumor. CASE 2: 12-year-old female adolescent, hospitalized due to pneumonia and low-back pain under study associated with weight loss. A retroperitoneal mass was diagnosed involving the right psoas muscle, paravertebral muscles, vertebrae, right kidney, and ipsilateral dia phragm. A puncture biopsy was performed and the result was compatible with an inflammatory myofibroblastic tumor. CASE 3: 11-year-old female pre-adolescent, hospitalized to study recurrent urinary tract infection. A bladder tumor was identified, and the biopsy showed compatibility with inflammatory myofibroblastic tumor. CONCLUSION: Due to the variable behavior of the inflammatory myofibroblastic tumor, its management will depend on the location, expression of the anaplastic lymphoma kinase (ALK), tumor behavior, and the resection possibility.

Diagnostic value of circulating lncRNA ANRIL and its correlation with coronary artery disease parameters

This study aimed to detect the expression of the long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) and evaluate its correlation with disease risk, stenosis degree, inflammation, as well as overall survival (OS) in coronary artery disease (CAD) patients. A total of 230 patients who underwent diagnostic coronary angiography were consecutively recruited and assigned to CAD group (n=125) or control group (n=105) according to presence or absence of CAD. Gensini score was calculated to assess the severity of coronary artery damage. Plasma samples were collected and the expression ANRIL was detected in all participants. High-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, IL-10, and IL-17 in CAD patients were measured and OS was calculated. The relative expression of ANRIL was higher in CAD patients compared to controls (P<0.001). Receiver operating characteristic disclosed that ANRIL could distinguish CAD patients from controls with an area under the curve of 0.789 (95%CI: 0.731-0.847). Spearman's rank correlation test revealed that expression of ANRIL was positively correlated with Gensini score (P=0.001), levels of hs-CRP (P=0.001), ESR (P=0.038), TNF-α (P=0.004), and IL-6 (P<0.001), while negatively correlated with IL-10 level (P=0.008) in CAD patients. Kaplan-Meier curve revealed that high expression of ANRIL was associated with shorter OS (P=0.013). In conclusion, circulating ANRIL presented a good diagnostic value for CAD, and its high expression was associated with increased stenosis degree, raised inflammation, and poor OS in CAD patients.

Diabetes Mellitus: sua influência na resposta inflamatória e na evolução clínica da sepse / Diabetes Mellitus: its influence on the inflammatory response and clinical evolution of sepsis

A sepse é manifestada por um conjunto de reações fisiológicas do organismo que ocorrem de maneira desregulada em resposta à uma infecção. A mortalidade por essa síndrome é de aproximadamente 60%, a depender da gravidade das manifestações clínicas. Nas Unidades de Terapia Intensiva (UTI), pelo menos 30% dos leitos são ocupados por pacientes com sepse e estima-se que após esse agravo, há um aumento da morbidade e do risco de óbito. O diabetes mellitus do tipo 2 (DM2) é uma comorbidade presente em 20% dos pacientes com sepse. O diabetes acomete 415 milhões de pessoas no mundo, com expectativas de aumento da prevalência nos próximos anos. Acredita-se que diabéticos são mais susceptíveis às infecções e apresentam diferenças nas defesas do organismo como a redução da fagocitose dos leucócitos, elevação dos níveis séricos de fator de necrose tumoral alfa, que associados podem acarretar a inflamação mais persistente, especialmente em face à sepse. O objetivo deste estudo foi analisar a influência da resposta inflamatória em cultura de sangue total e a evolução clínica de diabéticos e não diabéticos com sepse. A resposta inflamatória foi analisada por delineamento experimental, em culturas de sangue total ex vivo. Foram exploradas variáveis relativas ao perfil antropométrico, glicêmico, lipídico e inflamatório basal. Após as culturas de sangue serem estimuladas com lipopolissacarídeo, foram dosadas as concentrações de nitrato, atividade da enzima catalase e IL-10. A evolução clínica foi estudada por desenvolvimento não experimental do tipo coorte, em que foram avaliadas as características sociodemográficas, clínicas, laboratoriais e relativas à internação em uma UTI. Ambos os delineamentos incluíram grupos de pacientes: não diabéticos e diabéticos. No delineamento experimental 25 pacientes compuseram cada grupo. Observou-se diferenças estatísticas significantes em relação a idade, a presença e o número de comorbidades e os níveis de LDL, glicemia, Hb1Ac, concentrações de nitrato e nitrito basal. Nas culturas não se obsersou diferenças entre os grupos. No estudo de coorte, cada grupo foi composto por 102 pacientes. Os números de óbitos e de comorbidades, a gravidade/prognóstico na admissão e os índices glicêmicos foram mais elevados em pacientes diabéticos quando comparados com pacientes não diabéticos com sepse. O perfil inflamatório e metabólico basal difere em pacientes diabéticos e não diabéticos, mas a hipótese de que o DM2 influencia na resposta inflamatória não foi comprovada, entretanto, a evolução clínica foi diferente entre os grupos, com piores resultados para aqueles com DM2

Sepsis is manifested by a set of physiological reactions of the body that occur in an unregulated manner in response to an infection. Mortality from this syndrome is approximately 60%, depending on the severity of clinical manifestations. In Intensive Care Units (ICU), at least 30% of beds are occupied by patients with sepsis and it is estimated that after this worsening, there is an increase in morbidity and risk of death. Diabetes mellitus type 2 (T2DM) is a comorbidity present in 20% of patients with sepsis. Diabetes affects 415 million people worldwide, with expectations of increased prevalence in the coming years. It is believed that diabetics are more susceptible to infections and present differences in the body's defenses, such as reduction of leukocyte phagocytosis, increase in serum levels of alpha tumor necrosis factor, which may lead to more persistent inflammation, especially in the face of sepsis. The objective of this study was to analyze the influence of the inflammatory response in whole blood culture and the clinical evolution of diabetics and non-diabetics patients with sepsis. The inflammatory response was analyzed by experimental design, in ex vivo cultures of whole blood. Variables related to anthropometric, glycemic, lipidic and basal inflammatory profile were explored. After blood cultures were stimulated with lipopolysaccharide, nitrate concentrations, catalase enzyme activity and IL-10 were measured. The clinical evolution was studied by non-experimental cohort development, in which sociodemographic, clinical, laboratory and ICU-related characteristics were evaluated. Both designs included groups of patients: non-diabetic and diabetic. In the experimental design, 25 patients composed each group. Significant statistical differences were observed regarding age, presence and number of comorbidities and levels of LDL, glycemia, Hb1Ac, nitrate and basal nitrite concentrations. No differences between the groups were observed in the cultures. In the cohort study, each group was composed of 102 patients. The number of deaths and comorbidities, the severity/prognosis at admission and the glycemic indexes were higher in diabetic patients when compared to non-diabetic patients with sepsis. The basal inflammatory and metabolic profile differs in diabetic and non diabetic patients, but the hypothesis that DM2 influences the inflammatory response was not proven, however, clinical evolution was different between the groups, with worse results for those with T2DM

Osteomielitis crónica multifocal recurrente: caso clínico pediátrico / Chronic recurrent multifocal osteomyelitis: pediatric clinical case

La osteomielitis crónica multifocal recurrente fue recientemente clasificada dentro de las enfermedades autoinflamatorias, caracterizadas por episodios de inflamación sistèmica, que incluyen indicadores serológicos de inflamación, en ausencia de autoanticuerpos o agentes patógenos. La característica clínica es la aparición insidiosa de dolor, tumefacción y sensibilidad localizada sobre el hueso afectado, principalmente, en la metáfisis y epífisis de los huesos largos, clavícula y también vértebras. Son episodios autolimitados y recurrentes. Se presenta a un paciente de 2 años y 2 meses con afectación ósea tipo osteolítica en dos focos aislados con un año de diferencia entre ambos episodios. La biopsia ósea fue compatible con osteomielitis crónica y se descartó patología de origen infeccioso, neoplásico y enfermedad proliferativa. Presentó buena respuesta al tratamiento con antiinflamatorios. El conocimiento de esta entidad como diagnóstico diferencial evita el tratamiento antibiótico prolongado, estudios complementarios y biopsias óseas, considerando los criterios diagnósticos y recurrencia de los episodios.

Chronic recurrent multifocal osteomyelitis has recently been classified as an autoinflammatory disorder characterized by episodes of systemic inflammation including serological signs of inflammation occurring in the absence of autoantibodies or pathogen agents. The insidious onset of pain with swelling and tenderness localized over the affected bones are the main manifestations. The metaphysis and epiphyses of the long bones, clavicle and vertebrae are affected. We report a male patient aged 2 years and 2 months with osteomyelitis with lytic destruction in two different single sites with a year difference between the episodes. Histological examination of the bone showed inflammation and chronic osteomyelitis, excluding the existence of infectious osteomyelitis, neoplasm and myeloproliferative disease. Clinical symptoms improved under treatment with nonsteroidal anti-inflammatory drugs. Considering chronic recurrent multifocal osteomyelitis may shorten time to diagnosis in order to avoid potentially unnecessary prolonged courses of intravenous antibiotics, complementary studies and multiple biopsies.

Estado proinflamatorio en niños obesos / Proinflammatory state in obese children

INTRODUCCIÓN: La presencia de un estado de inflamación de bajo grado en niños obesos, se debería, entre otros factores, a que el tejido adiposo de los obesos produce moléculas proinflamatorias que contribuyen al desarrollo de aterosclerosis. OBJETIVO: Determinar en una población de niños obesos los niveles séricos de ligando CD-40 soluble (sCD40L), proteína quimioatractante de monocitos 1 (MCP-1), interleuquina 6 (IL-6), Factor de Necrosis tumoral a (TNF-a) y Proteína C Reactiva ultrasensible (PCR-us), comparados con un grupo control y analizar la correlación de estas moléculas con las variables antropométricas y metabólicas. PACIENTES Y MÉTODO: Estudio transversal de 37 niños obesos de 8 a 12 años y 20 niños con peso normal. A todos los pacientes se les realizó una historia clínica consignando edad, peso, talla, IMC, circunferencia de cintura, estadios de Tanner y antecedentes familiares. Se determinaron los niveles séricos de sCD40L, MCP-1, IL-6, TNF-a y PCR-us mediante ELISA, PCR-us por quimioluminiscencia, glucemia, insulina plasmática, perfil lipídico y se calculó el índice HOMA. Los datos se expresaron como la mediana y rango intercuartil y se utilizó el coeficiente de Spearman para investigar las correlaciones entre variables. RESULTADOS: Los niños obesos presentaron valores significativamente mayores de sCD40L, MCP-1, IL-6, TNF-a, PCR-us que los niños controles. El índice de masa corporal y la circunferencia de cintura se correlacionaron positivamente con sCD40L y MCP-1. CONCLUSIÓN: Los niveles elevados de las moléculas estudiadas sugieren la presencia de inflamación de bajo grado asociada a obesidad en esta población.

INTRODUCTION: Obesity is a chronic disease that affects adults as well as children and is associated with insulin resistance, type 2 diabetes and cardiovascular disease. One of the reasons for the presence of low-grade inflammation in these patients could be that adipose tissue of the obese produces proin flammatory molecules that favor the development of atherosclerosis. OBJECTIVE: To determine serum levels of soluble CD40 ligand (sCD40L), monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), Tumor Necrosis Factor alpha (TNF-Α) and high sensitivity CRP (hsCRP), in an obese chil dren population compared to a control group, also to analyze the correlation of these molecules with the anthropometric and metabolic variables. PATIENTS AND METHOD: A cross-sectional, observational study was carried out on 37 obese children, aged 8 to 12 years, and 20 children with normal weight. Serum levels of sCD40L, MCP-1, IL-6, TNF-Α and hsCRP were determined. Data were expressed as the median and interquartil range and Spearman coefficient was used to investigate correlations between variables. RESULTS: Compared to the control group, obese children presented significantly higher values of sCD40L, MCP-1, IL-6, TNF-Α, and hsCRP than control group. Body mass index and waist circumference correlated positively with sCD40L and MCP-1. CONCLUSION: Elevated levels of the studied molecules studied suggest the presence of low-grade inflammation associated with obesity in this population.

A prospective randomized study of the inflammatory responses to multiport and singleport laparoscopic hysterectomies

Abstract Purpose: To evaluate the inflammatory responses induced by laparoscopic hysterectomies with multiport and singleport approaches. Methods: This was a pilot prospective randomized study that included 42 women candidates for hysterectomy at School of Medicine, Hospital das Clínicas, USP. The patients were randomized to two groups: MP-TLH (total laparoscopic hysterectomy with 3 abdominal incisions), and SP-TLH (total laparoscopic hysterectomy with a single umbilical incision).We evaluated the inflammatory response (via CRP, IL-6, IL-10, TNFα, VEGF and leukogram assessments), surgical time, postoperative pain, blood loss and surgical complications in both groups. Results: Both techniques were similar regarding C-reactive protein (p=.666), IL-6 (p=.833), IL-10 (p=.420), TNF-α(p=.098), VEGF (p=.092) and the leukogram (p=.712) measures. The operative time was significantly longer in the SP-TLH group than in the MP-TLH group (p=.001). The pain evaluation was similar in both groups (p=.170). Hemoglobin variation and the aspirated blood volume were similar in both groups (p=.493 and p=.347). There were no major complications. Conclusions: Multiport and singleport laparoscopic approaches are both safe methods for hysterectomy. Although SP-TLH resulted in a significantly longer operative time than MP-TLH, no differences were observed between the groups in inflammatory responses, blood loss and postoperative pain.

Skin symptoms as diagnostic clue for autoinflammatory diseases

ABSTRACT Autoinflammatory disorders are immune-mediated diseases with increased production of inflammatory cytokines and absence of detectable autoantibodies. They course with recurrent episodes of systemic inflammation and fever is the most common symptom. Cutaneous manifestations are prevalent and important to diagnosis and early treatment of the syndromes. The purpose of this review is to emphasize to dermatologists the skin symptoms present in these syndromes in order to provide their early diagnosis.

Differences in Hepatic Expression of Iron, Inflammation and Stress-Related Genes in Patients with Nonalcoholic Steatohepatitis

Abstract: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. We have previously shown that hepatic reticuloendothelial system (RES) iron deposition is associated with an advanced degree of nonalcoholic steatohepatitis (NASH) in humans. In this study, we aimed to determine differentially expressed genes related to iron overload, inflammation and oxidative stress pathways, with the goal of identifying factors associated with NASH progression. Seventy five patients with NAFLD were evaluated for their biochemical parameters and their liver tissue analyzed for NASH histological characteristics. Gene expression analysis of pathways related to iron homeostasis, inflammation and oxidative stress was performed using real-time PCR. Gene expression was compared between subjects based on disease status and presence of hepatic iron staining. We observed increased gene expression of hepcidin (HAMP) (2.3 fold, p = 0.027), transmembrane serine proteinase 6 (TMPRSS6) (8.4 fold, p = 0.003), signal transducer and activator of transcription 3 (STAT3) (5.5 fold, p = 0.004), proinflammatory cytokines; IL-1β (2.7 fold, p = 0.046) and TNF-α (3.8 fold, p = 0.001) in patients with NASH. TMPRSS6, a negative regulator of HAMP, is overexpressed in patients with NASH and HIF1α (hypoxia inducible factor-1) is downregulated. NAFLD patients with hepatic iron deposition exhibited higher hepcidin expression (3.1 fold, p = 0.04) but lower expression of cytokines. In conclusion, we observed elevated hepatic HAMP expression in patients with NASH and in NAFLD patients who had hepatic iron deposition, while proinflammatory cytokines displayed elevated expression only in patients with NASH, suggesting a regulatory role for hepcidin in NAFL to NASH transition and in mitigating inflammatory responses.

Clinical and Metabolic Effects of two Periodontal Therapeutic Modalities in Diabetic Patients with Residual Pockets

Objective: To evaluate the metabolic control and compare the clinical effects between non-surgical and surgical therapies on periodontal treatment of residual pockets of type 2 diabetic patients. Material and Methods: 352 periodontal sites in 16 type 2 diabetic subjects with residual pockets of similar depths were randomly selected, whose contralateral quadrants were divided into G1 and G2 undergoing surgical and nonsurgical therapy, respectively, and evaluated 3 and 6 months after the first intervention. The data were analyzed by Statistical Package of Social Science (SPSS) version 20.0, using descriptive and inferential statistical methods. Fisher's exact test was used to verify differences between means obtained in the clinical parameters between G1 and G2. The significance level adopted was 5%. Results: The mean Hb1Ac values of patients were significantly reduced and the mean PD and CIL values were reduced in G1 with no significant difference when compared to G2. Conclusion: Periodontal treatment was effective in metabolic control of type 2 diabetic patients and that both therapies, surgical and non-surgical, behaved similarly when compared.

Patogênese da Doença de Chagas na era atual - microrganismos e micropartículas / The present-day pathogenesis of Chagas Disease - microorganisms and microparticles

A presente revisão descreve os principais achados anatomopatológicos que caracterizam a cardiopatia chagásica crônica, discute a teoria autoimune e parassimpaticopriva que dominaram a explicação patogenética nas ultimas décadas e propõe novos caminhos a partir de achados mais recentes. Esses achados se relacionam com a presença de outros microrganismos que talvez tenham sejam levados até o miocárdio por estarem em simbiose com o T. cruzi, como micoplasmas, clamídias e arqueias. As arqueias têm como característica aumentar a inflamação por apresentarem antígenos aos linfócitos T CD8+. A inflamação exacerbada pode levar à vasodilatação da microcirculação e à falha na distribuição de sangue no miocárdio, ocasionando áreas de isquemia em regiões distais de dupla irrigação. Isto explicaria as regiões de afilamento e dilatação aneurismática ventricular, bem como a fibrose e infiltração gordurosa do sistema de condução (feixe de His, nó sinoatrial e atrioventricular). Esses microrganismos no interior da fibra cardíaca podem induzir uma resposta imunológica com fibrose ao redor dos cardiomiócitos, os quais se tornam extremamente hipertróficos por não entrarem em apoptose. A simbiose entre esses microrganismos pode levar à produção de micropartículas infecciosas que circulam e fazem parte da patogenia da descompensação cardíaca. Assim, a ação terapêutica na doença de Chagas deveria incluir a eliminação simultânea desses diferentes microrganismos e não somente do T. cruzi

This review describes the main anatomopathological findings that characterize chronic Chagasic cardiomyopathy, discusses the autoimmune and parasympathetic dysautonomia theories that have dominated the pathogenic explanation in recent decades, and proposes new routes based on the most recent findings. These findings relate to the presence of other microorganisms, such as micoplasmas, chlamydias and archaea, that are perhaps carried to the myocardium as they are in symbiosis with T. cruzi. A characteristic of archaea is that they increase inflammation by presenting T CD8+ lymphocyte antigens. Exacerbated inflammation may lead to vasodilation of the microcirculation and failure of blood distribution in the myocardium, leading to areas of ischemia in distal regions of double irrigation. This would explain the regions of thinning and dilation of the ventricular aneurysm, as well as the fibrosis and fatty infiltration of the conduction system (His bundle, sinoatrial node and atrioventricular node). These microorganisms in the interior of the heart fiber may lead to an immunological response with fibrosis around the cardiomyocytes, which become extremely hypertrophic, as they do not enter apoptosis. The symbiosis between these microorganisms can lead to the production of infectious microparticles that circulate and form part of the pathogenesis of decompensated heart failure. The therapeutic conduct in Chagas disease should therefore include the simultaneous elimination of these different microorganisms, and not only of T. cruzi