Proteína C reactiva y su progresión en el tiempo para la detección de las fugas anastomóticas / C-reactive protein and its progression over time for the detection of anastomotic leaks

Introducción. Las fugas anastomóticas son una complicación común y crítica en cirugía gastrointestinal, por lo que su identificación y tratamiento temprano son necesarios para evitar resultados adversos. El uso convencional con un valor límite de la proteína C reactiva ha demostrado una utilidad limitada. El objetivo de este estudio fue determinar la utilidad de la medición seriada de la proteína C reactiva en la detección de fugas anastomóticas. Métodos. Revisión prospectiva de base de datos retrospectiva de pacientes sometidos a cirugía abdominal mayor con al menos una anastomosis intestinal. Se midió la proteína C reactiva al tercer y quinto día posoperatorio. Las complicaciones se categorizaron según la clasificación de Clavien-Dindo. La precisión diagnóstica fue evaluada por el área bajo la curva. Resultados. Se incluyeron 157 pacientes, el 52 % mujeres. La edad promedio fue de 63,7 años. El mayor número de cirugías correspondió a gastrectomía (36,3 %), resección anterior de recto (15,3 %) y hemicolectomía derecha (13,4 %). El 25,5 % tuvieron alguna complicación postoperatoria y el 32,5 % (n=13) presentaron fuga en la anastomosis. El aumento de la proteína C reactiva tuvo un área bajo la curva de 0,918 con un punto de corte de aumento en 1,3 mg/L, sensibilidad de 92,3 % (IC95% 78 ­ 100) y una especificidad de 92,4 % (IC95% 88 ­ 96). Conclusiones. El aumento de 1,3 mg/L en la proteína C reactiva entre el día de la cirugía y el quinto día fue un predictor preciso de fugas anastomóticas en pacientes con cirugía abdominal mayor

Introduction. Anastomotic leaks are a common and critical complication in gastrointestinal surgery. Their identification and early treatment are necessary to avoid adverse results, and conventional use with a cutoff value of C-reactive protein has shown limited utility. The objective of this study was to determine the usefulness of serial measurement of C-reactive protein in the detection of anastomotic leaks. Methods. Prospective review of a retrospective database of patients undergoing major abdominal surgery with at least one intestinal anastomosis. C-reactive protein was measured on the third and fifth postoperative days. Complications were classified according to the Clavien-Dindo classification. Diagnostic accuracy was evaluated by the area under the curve.Results. 157 patients were included, 52% were females. The average age was 63.7 years. The largest number of surgeries corresponded to gastrectomies (36.3%), anterior resection of the rectum (15.3%) and right hemicolectomies (13.4%). 25.5% had some postoperative complication and 32.5% (n=13) had anastomosis leaks. The increase in C-reactive protein had an area under the curve of 0.918 with an increase cut-off point of 1.3 mg/L, sensitivity of 92.3% (95% CI 78-100) and specificity of 92.4%. (95% CI 88-96). Conclusions. The 1.3 mg/L increase in C-reactive protein between the day of surgery and the fifth day was an accurate predictor of anastomotic leaks in patients with major abdominal surgery

Eficacia de la atorvastatina en el infarto cerebral aterotrombótico agudo / Effectiveness of atorvastatin in acute atherothrombotic cerebral infartation

Introducción: Las enfermedades Cerebrovasculares constituyen un importante problema de salud a escala global y en Cuba ocupan la tercera causa de muerte y la primera causa de discapacidad. Objetivo: Evaluar el uso de atorvastatina en el infarto cerebral aterotrombótico agudo. Métodos: Se realizó un estudio prospectivo longitudinal en los pacientes que acudieron al cuerpo de guardia del Hospital Clínico Quirúrgico Julio Trigo López diagnosticados como infarto cerebral aterotrombótico agudo. De forma aleatoria y con previo consentimiento informado se les suministró una dosis de 0, 20 mg o 40 mg de atorvastatina. Se les realizó tomografía axial computarizada de cráneo, la cual fue repetida al tercer día y a los 30 días. Se determinó el valor de proteína C reactiva en el cuerpo de guardia, y a los 30 días fueron evaluados clínicamente de acuerdo a la escala de National Institute of Health Stroke Scale en cuerpo de guardia, diariamente durante su ingreso y 30 días después. Resultados: El tamaño del área infartada disminuyó un 19,4 por ciento con 40 mg de atorvastatina al igual que el valor de proteína C reactiva que se redujo en 16 mg/L. La evaluación clínica según la escala de National Institute of Health Stroke Scale mostró una reducción en más de 8 puntos de acuerdo a la dosis de atorvastatina empleada. Conclusiones: Se demostró la eficacia de la atorvastatina por la disminución del área infartada, la reducción de los valores de proteína C reactiva y la evolución clínica favorable. Todos estos factores fueron directamente proporcional a la dosis de atorvastatina empleada(AU)

Introduction: Cererovascular diseases represent an important health problem worldwide and in Cuba they rank the third cause of death and the first cause of disability. Objective: To evaluate the use of astorvastin in acute atherotrombotic cerebral infactation. Methods: A longitudinal prospective study was carried out in patients who attended the emergency room of Julio Trigo López Surgical Clinical Hospital diagnosed with acute atherothrombotic cerebral infarction. Randomly and with prior informed consent, they were given a dose of 0, 20 mg or 40 mg of atorvastatin. Computerized axial tomography of the skull was performed, which was repeated on day 3 and day 30. The value of C-reactive protein in the emergency room was determined, and at day 30, they were clinically evaluated daily during admission and 30 days later, according to the scale of the National Institute of Health Stroke Scale in emergency room. Results: The size of the infarcted area decreased by 19.4 percent with 40 mg of atorvastatin, as well as the value of C-reactive protein, which decreased by 16 mg/L. The clinical evaluation according to the National Institute of Health Stroke Scale showed reduction of more than 8 points according to the dose of atorvastatin used. Conclusions: The efficacy of atorvastatin was demonstrated by the reduction of the infarcted area, the reduction of C-reactive protein values and the favorable clinical evolution. All of these factors were directly proportional to the dose of atorvastatin used(AU)

Clinical manifestations and gene analysis of 18 cases of hereditary protein S deficiency / 中华血液学杂志

Objective: To analyze the clinical manifestations and molecular pathogenesis of 18 patients with inherited protein S (PS) deficiency. Methods: Eighteen patients with inherited PS deficiency who were admitted to the Institute of Hematology & Blood Diseases Hospital from June 2016 to February 2019 were analyzed: activity of protein C (PC) and antithrombin (AT) , PS activity were measured for phenotype diagnosis; high throughput sequencing (HTS) was used for screening of coagulation disease-related genes; Sanger sequencing was used to confirm candidate variants; Swiss-model was used for three-dimensional structure analysis. Results: The PS:C of 18 patients ranged from 12.5 to 48.2 U/dL. Among them, 16 cases developed deep vein thrombosis, including 2 cases each with mesenteric vein thrombosis and cerebral infarction, and 1 case each with pulmonary embolism and deep vein thrombosis during pregnancy. A total of 16 PROS1 gene mutations were detected, and 5 nonsense mutations (c.134_162del/p.Leu45*, c.847G>T/p.Glu283*, c.995_996delAT/p.Tyr332*, c.1359G> A/p.Trp453*, c.1474C>T/p.Gln492*) , 2 frameshift mutations (c.1460delG/p.Gla487Valfs*9 and c.1747_1750delAATC/p.Asn583Wfs*9) and 1 large fragment deletion (exon9 deletion) were reported for the first time. In addition, the PS:C of the deep vein thrombosis during pregnancy case was 55.2 U/dL carrying PROC gene c.565C>T/p.Arg189Trp mutation. Conclusion: The newly discovered gene mutations enriched the PROS1 gene mutation spectrum which associated with inherited PS deficiency.

Clinical phenotype and gene mutation analysis of 12 patients with hereditary protein C deficiency in different families / 中华血液学杂志

Objective: To investigate the molecular pathogenesis and clinical features of unrelated 12 patients with inherited coagulation protein C (PC) deficiency in Chinese population. Methods: The PC activity (PC:A) and PC antigen (PC:Ag) were detected by chromogenic substrate and enzyme linked immunosorbent assay, respectively. The nine exons and flanking sequences of the protein C (PROC) gene were amplified by polymerase chain reaction with direct sequencing, and the suspected mutations were validated by reverse sequencing (clone sequencing for deletion mutations) . Results: The PC:A of the 12 probands decreased significantly, ranging from 18% to 55%, and the PC:Ag of the 10 probands decreased significantly. Eleven mutations were found, out of which four mutations [c.383G>A (p.Gly128Asp) , c.997G>A (p.Ala291Thr) , c.1318C>T (p.Arg398Cys) , and c.532G>C (p.Leu278Pro) ] were discovered for the first time. Six mutations were in the serine protease domain, four mutations were located in epidermal growth factor (EGF) -like domains, and one mutation was located in activation peptide. There were two deletion mutations (p.Met364Trp fsX15 and p.Lys192del) , and the rest were missense mutations. Mutations p.Phe181Val and p.Arg189Trp were identified in three unrelated families. All mutations may be inherited, and consanguineous marriages were reported in two families. Among the probands, nine cases had venous thrombosis, two cases had poor pregnancy manifestations, and one case had purpura. Conclusion: Patients with PC deficiency caused by PROC gene defects are prone to venous thrombosis, especially when there are other thrombotic factors present at the same time.

Efeitos do método pilates sobre a capacidade funcional, fatores antropométricos, marcadores inflamatórios e qualidade de vida em idosas sedentárias / Effects of the pilates method on functional capacity, anthropometric factors, inflammatory markers and quality of life in sedentary elderly women

O objetivo do presente estudo foi investigar os efeitos de exercícios físicos baseados no método Pilates solo sobre a capacidade funcional, fatores antropométricos, níveis de marcadores inflamatórios circulantes e a qualidade de vida em idosas sedentárias. Trata­se de um delineamento quase experimental com pré e pós teste. A amostra foi constituída por 33 mulheres idosas com idade igual ou superior a 60 anos. Para avaliar a capacidade funcional (CF) foram utilizados os testes de velocidade de caminhada (VC) e de força de preensão manual (FPM). Para avaliar a presença de marcadores inflamatórios foram realizados exames laboratoriais a fim de quantificar os níveis séricos de proteína C reativa ultrassensível (PCR-us) e fibrinogênio. E para avaliar a qualidade de vida (QV) foi utilizado o questionário SF ­ 36. Na análise estatística utilizou-se o teste de normalidade Shapiro Wilk. Para os dados paramétricos teste t pareado e ANOVA one Way e, para os dados não paramétricos, o teste Wilcoxon e Kruskal-Wallis. O teste Qui-Quadrado foi utilizado para analises de associações. Os dados foram analisados pelo no programa SPSS-IBM, versão 22.0 devidamente registrado. O nível de significância adotado foi de p≤0,05. O grupo Pilates não apresentou alterações estatisticamente significativas em relação à CF (p>0,05), porém as demais variáveis apresentaram diferença significativa. Para variáveis antropométricas, PCR e fibrinogênio (p < 0,05); e QV, dois domínios apresentaram alterações significativas: limitações por aspectos físicos (p=0,045) e dor (p=0,011). Conclui-se que a prática do método Pilates solo promoveu redução significativa sobre a composição corporal, sobre os níveis séricos de marcadores inflamatórios, sobre a qualidade de vida e manutenção da capacidade funcional de idosas sedentárias. (AU)

The aim of the present study was investigate the effects of exercises based on the Pilates method on functional capacity, anthropometric factors, levels of circulating inflammatory markers and quality of life in sedentary elderly women. It is an almost experimental design with pre and post-test. The sample considered of 33 elderly individuals, aged 60 years and female. In order to evaluate the functional capacity (FC), the tests of walking speed (WS) and manual grip strength (MGS) were used; to evaluate the presence of inflammatory markers, laboratory tests were performed to quantify the serum levels of C-reactive protein and fibrinogen, and the SF-36 questionnaire was used to evaluate the quality of life. For statistical analysis, Shapiro Wilk normality test was used. For parametric data, paired t- test and one-way ANOVA were used, and for nonparametric data, the Wilcoxon and Kruskal -Wallis test. Chi-square test was used for association analysis. All data were analyzed by SPSS-IBM, version 22.0 duly registered and the significance level of p ≤0.05 was stipulated. The Pilates group did not present significant alterations in relation to CF (p> 0.05), but the other variables presented. Anthropometric variables (total body mass, BMI, waist and hip circumference), C-reactive protein and fibrinogen (p< 0,05); and in relation to QV, two domains presented significant changes: limitations by physical aspects (p = 0.045) and pain (p = 0.011). It was concluded that the Pilates solo practice promoted a significant reduction in body composition, serum levels of inflammatory markers, quality of life and maintenance of functional capacity

Comparative Study of the Level of Inflammatory Factors of Erythrocyte Sedimentation Rate and Reactive Protein C in Benign and Malignant Thyroid Nodules

ABSTRACT Objective: To evaluate the level of inflammatory factors of erythrocyte sedimentation rate and reactive protein C in benign and malignant thyroid nodules. Material and Methods: In this case-control study, patients who were referred because of an enlarged thyroid gland were selected, patients who had undergone surgery for the thyroid nodule were included in the study. Erythrocyte sedimentation rate and reactive protein C were measured before surgery in patients who were candidates for thyroid surgery. The histopathological records of patients were retrospectively reviewed. Relevant cases had a cytological evaluation of thyroid nodules by fine-needle aspiration cytology (FNAC). The mean of ESR / CRP in both groups was compared using an independent t-test (p>0.05). Results: In malignant tumor type, in all patients, with Pill (PTC), analyzes in the malignant group showed a significant difference between the mean ESR / CRP in both groups with and without thyroid history. Sub-analyzes in the malignant group were significantly different between the mean ESR / CRP in both groups with and without thyroid histories (p=0.009) (40.16 ± 28.81). The association between ESR and CRP, ESR / CRP and tumor size, ESR / CRP and age in each group as well as in the whole patients were evaluated using Pearson correlation test, which showed a positive association between ESR age and ESR (p=0.024, r=0.375). In the malignant group, a negative correlation was found between the age and the CRP rate (p=0.027, r=-0.441), and in the total patients between the age and the rate (ES=0.043, r=-0.256). Conclusion: Factors such as ESR and CRP, which are considered acute phase reactors and their levels increase in acute inflammatory conditions, may not have a significant increase in chronic inflammatory conditions and malignancies.

Genetic and Clinical Characteristics of A Family with Combined PROC and PROS1 Genetic Variants / 中国实验血液学杂志

OBJECTIVE@#To test the anticoagulation functions, perform the genetic diagnosis and analyze the clinical characteristics in a family with combined heterozygous genetic variants of PROC and PROS1.@*METHODS@#Peripheral blood was collected from all the family members. Hematological phenotypes and activity of anticoagulant factors were analyzed. Target genes were amplified by PCR from DNA isolated from peripheral blood, and then were analyzed by Sanger DNA sequencing.@*RESULTS@#Many members in the family displayed the combined genetic variants in protein C and protein S, and six family members accompanied by deep venous thrombosis (DVT). The influences of genetic and secondary factors on the incidence of venous thrombosis in the family members were analyzed. The results showed that in this family, carriers of combined protein C and protein S gene defects had a higher incidence of VTE, but acquired factors still played a key role in the eventual thrombotic symptoms.@*CONCLUSION@#Venous thromboembolism (VTE) is a multifactorial disease, the combined genetic heterozygous mutations of protein C and S is an important genetic factor, and the clinical phenotype show a high heterogenicity, the secondary factors contribute to the VTE incidence.

Valor predictivo de proteína C reactiva y albúmina en la expulsión de litos ureterales de 6-10 mm del tercio inferior / Predictive Value of C-reactive Protein and Albumin in the Expulsion of Ureteral Stones (6-10 mm) from the Lower Third

Introducción La litiasis ureteral es responsable del 20% de casos de urolitiasis, el cólico renal afecta negativamente la calidad de vida, el mayor dilema es el elegir entre medidas conservadoras y cirugía. La mayoría de los litos ureterales de tercio distal menor de 6mm, pueden pasar espontáneamente con terapia conservadora. Sin embargo, ella se asocia a incomodidad, infecciones y ausencia laboral. La proteína C Reactiva (PCR) se ha utilizado como predictor en la expulsión de esos litos, además se introduce el uso de la albúmina como nuevo marcador de predicción. Objetivo El objetivo es analizar el valor predictivo de PCR y albúmina para la expulsión de litos ureterales de tercio inferior de 6­10 mm. Métodos Se realizó un estudio prospectivo en pacientes que presentaron cólico renal secundario a litiasis ureteral distal 6­10 Mm, los cuales recibieron tratamiento médico expulsivo durante 4 semanas, hasta la expulsión del lito o la necesidad de tratamiento quirúrgico en que se determinó punto de corte de PCR y albúmina por medio de una curva COR. Resultados 78 pacientes se enrolaron en el estudio, el paso espontáneo fue de 55,1% y el restante requirió de intervención quirúrgica, el punto de corte para PCR fue 5,95 mg/L y de 2,75 g/dl para albúmina. Conclusión El PCR es un parámetro predictivo en la expulsión de litos ureterales de tercio inferior en pacientes muy seleccionados. Se obtiene el siguiente punto de corte para predecir la eliminación del lito (5,95 mg/L) y se propone la albúmina como un nuevo parámetro bioquímico.

Introduction Ureteral stones is responsible for 20% of cases of urolithiasis, renal colic negatively affects quality of life, the main dilemma is choosing between conservative measures and surgery. Most ureteral stones of the distal third smaller than 6 mm can pass spontaneously with conservative therapy. However, this is associated with discomfort, infections. C Reactive protein (CRP) has been used as a predictor in the expulsion of these stones, and the use of albumin as a new marker of prediction is also introduced. Objective The objective is to analyze the predictive value of CRP and albumin for the expulsion of ureteral stones of the lower third of 6­10 mm Methods A prospective study was performed in patients who presented renal colic secondary to distal ureteral lithiasis 6­10 mm and who received medical expulsive treatment for 4 weeks, until the expulsion of the stone or the need for surgical treatment, PCR cut off point was determined and albumin by means of a ROC curve. Results 78 patients enrolled in the study, spontaneous passage was 55.1% and the remaining required surgical intervention, the cut-off point for PCR was 5.95 mg/L and 2.75 g/dl for albumin. Conclusion CRP is a predictive parameter in the expulsion of lower third ureteral stones in highly selected patients. The following cut off point is obtained to predict the elimination of lithium (5.95 mg/L) and albumin is proposed as a new biochemical parameter.

Medicina de precisión en sepsis: utilidad de los en sepsis: utilidad de los biomarcadores en pacientes críticamente enfermos / Precision medicine in sepsis: usefulness of biomarkers In critically ill patientsbiomarkers In critically ill patients

Durante años la evolución del cuidado intensivo ha intentado ofrecer una atención basada en protocolos y paquetes de manejo agrupados por patologías y cuadro sindromáticos. Aunque se logró disminuir la mortalidad en diferentes patologías (sepsis y síndromes coronario agudo y de distrés respiratorio agudo), no se han resuelto por completo los problemas clínicos, en especial el diagnóstico y el manejo. Una nueva opción ha surgido en el horizonte denominada "medicina de precisión", entendida como estrategia de prevención y tratamiento que tiene en cuenta la variabilidad individual. La sepsis es un síndrome con múltiples aristas en cuanto al fenotipo y genotipo, cuyo diagnóstico temprano es relevante para los desenlaces clínicos. Hasta el momento el enfoque principal ha sido la identificación de un germen etiológico para diferenciarla del síndrome de respuesta inflamatoria sistémica (SIRS). En los últimos años el paradigma en enfermedades infecciosas ha cambiado debido a estudios que demuestran como la respuesta inmunitaria del paciente séptico tiene un papel clave en el desarrollo de la enfermedad, con implicaciones en el diagnóstico, pronóstico y tratamiento, que podrían ayudar a cambiar el abordaje en los próximos años gracias a una estrategia basada en medicina de precisión. Hoy los aislamientos microbiológicos y los cultivos siguen siendo el estándar de referencia con varias desventajas como el tiempo para obtener resultados, sobre todo en infecciones por gérmenes resistentes u hongos, que pueden retrasar el inicio de la terapia antimicrobiana. Como alternativa se ha planteado el uso de biomarcadores en sepsis que, siendo productos de la respuesta inflamatoria del individuo ante la infección, son útiles para el diagnóstico y pronóstico primordialmente en los críticamente enfermos. Decidimos realizar esta revisión narrativa acerca de la utilidad de los biomarcadores en pacientes con sepsis críticamente enfermos, para enfocarlos en un modelo de medicina personalizada.

For many years, critical care practice has been based on protocols and management guidelines categorized by pathologies or syndromes. Although mortality caused by various diseases such as sepsis, acute coronary syndrome and acute respiratory distress has decreased, clinical problems, particularly diagnosis and management, have not been completely resolved. A new option known as "precision medicine" is on the horizon, a prevention and treatment strategy based on individual variability. Sepsis is a syndrome encompassing multiple clinical phenotypes and genotypes coding and a prompt diagnosis is relevant to obtain better outcomes. To this moment the main approach has been the identification of microorganisms causing sepsis to distinguish sepsis from systemic inflammatory response (SIRS). Infectious diseases paradigm has changed during recent years due to studies demonstrating how septic patient immune response plays a key role in the development of the disease, with implications on diagnosis, prognosis and treatment, which may help change the approach in the next years thanks to a strategy based on precision medicine. Today microbiological identification and cultures continue to be the reference standard with several disadvantages such as turnaround time for test results predominantly in infections caused by resistant bacteria or fungi that may delay commencement of antibiotic therapy. The use of sepsis biomarkers determined by the individual ́s inflammatory response to infection have been proposed as a useful alternative for establishing diagnosis and prognosis mainly in critically ill patients. We decided to conduct this narrative review on the usefulness of biomarkers in critically ill septic patients using a personalized medicine model.

The effect of activated protein C in the experimental disseminated intravascular coagulation model formed by lipopolysaccharide infusion

Abstract Purpose: In this experimental study, activated protein C (APC), which has anticoagulant, antithrombotic, profibrinolytic, anti-inflammatory and antiapoptotic properties, was used to prevent coagulopathy in a disseminated intravascular coagulation (DIC) model formatted with lipopolysaccharide (LPS) infusion. Methods: Twenty-five Wistar albino rats weighting 280 - 320 g each were used. They were randomly divided into three groups: sham, control and study groups. To sham group (n = 5), only normal saline was infused. To control (n = 10) and study groups (n = 10), 30 mg/kg LPS was infused for 4 h from femoral vein. After LPS infusion, 100 µg/kg recombinant APC was given during 4 h in study group. Eight hours later, blood samples were taken from abdominal aorta and the animals sacrificed. From these samples, platelet, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer levels were studied. Results: Platelet counts and fibrinogen levels were significantly lower in control and study groups than sham group (p < 0.05). The PT, aPTT and D-dimer levels were significantly higher in control and study groups than in sham group (p < 0.05). When comparing control and study groups, platelet counts were not statistically different (p = 0.36). However, the difference of the fibrinogen levels was significant between these groups (p = 0.0001). While PT and aPTT were longer in the study group compared to the control group (p < 0.05), D-dimer levels were lower in the study group than in control (p = 0.0001). Conclusion: Use of APC can prevent hypercoagulation and consumption coagulopathy in the DIC as a result of correcting hematological parameters other than prolongation of coagulation time.

Human acute Chagas disease: changes in factor VII, activated protein C and hepatic enzymes from patients of oral outbreaks in Pará State (Brazilian Amazon)

Oral transmission of Chagas disease has been increasing in Latin American countries. The present study aimed to investigate changes in hepatic function, coagulation factor levels and parasite load in human acute Chagas disease (ACD) secondary to oral Trypanosoma cruzi transmission. Clinical and epidemiological findings of 102 infected individuals attended in the State of Pará from October 2013 to February 2016 were included. The most common symptoms were fever (98%), asthenia (83.3%), face and limb edema (80.4%), headache (74.5%) and myalgia (72.5%). The hepatic enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of 30 ACD patients were higher compared with controls, and this increase was independent of the treatment with benznidazole. Moreover, ACD individuals had higher plasma levels of activated protein C and lower levels of factor VII of the coagulation cascade. Patients with the highest parasite load had also the most increased transaminase levels. Also, ALT and AST were associated moderately (r = 0.429) and strongly (r = 0.595) with parasite load respectively. In conclusion, the present study raises the possibility that a disturbance in coagulation and hepatic function may be linked to human ACD.

Heterogeneity of Human γδ T Cells and Their Role in Cancer Immunity

The γδ T cells are unconventional lymphocytes that function in both innate and adaptive immune responses against various intracellular and infectious stresses. The γδ T cells can be exploited as cancer-killing effector cells since γδ TCRs recognize MHC-like molecules and growth factor receptors that are upregulated in cancer cells, and γδ T cells can differentiate into cytotoxic effector cells. However, γδ T cells may also promote tumor progression by secreting IL-17 or other cytokines. Therefore, it is essential to understand how the differentiation and homeostasis of γδ T cells are regulated and whether distinct γδ T cell subsets have different functions. Human γδ T cells are classified into Vδ2 and non-Vδ2 γδ T cells. The majority of Vδ2 γδ T cells are Vγ9δ2 T cells that recognize pyrophosphorylated isoprenoids generated by the dysregulated mevalonate pathway. In contrast, Vδ1 T cells expand from initially diverse TCR repertoire in patients with infectious diseases and cancers. The ligands of Vδ1 T cells are diverse and include the growth factor receptors such as endothelial protein C receptor. Both Vδ1 and Vδ2 γδ T cells are implicated to have immunotherapeutic potentials for cancers, but the detailed elucidation of the distinct characteristics of 2 populations will be required to enhance the immunotherapeutic potential of γδ T cells. Here, we summarize recent progress regarding cancer immunology of human γδ T cells, including their development, heterogeneity, and plasticity, the putative mechanisms underlying ligand recognition and activation, and their dual effects on tumor progression in the tumor microenvironment.

Protein C and S deficiency as a cause of mesenteric thrombosis: Differential diagnosis of systemic vasculitis / Deficiencia de proteínas C y S como causa de trombosis mesentérica: diagnóstico diferencial de las vasculitis sistémicas

ABSTRACT Acute mesenteric ischemia is a medical emergency that accounts for less than 1/1000 hospital admissions. The disease affects adults older than 50 years predominantly with cardiac compromise, in whom the presence of acute abdominal pain is the cardinal manifestation, and should make the clinician suspect this entity. Its presentation in adolescents is unusual; therefore, in these cases, the possibility of an underlying thrombophilia should be part of the differential diagnosis. The case is presented here of a young female with a protein C and S deficiency as the cause of mesenteric thrombosis.

RESUMEN La isquemia mesentérica aguda es una urgencia médica que se presenta en menos de 1/1.000 ingresos hospitalarios. Es una entidad clínica infrecuente, predominante en adultos mayores de 50 arios con afectación cardíaca, en quienes la presencia de dolor abdominal agudo es la manifestación cardinal y debería hacer sospechar dicho diagnóstico. La presentación en adolescentes es inusual, por lo que, en estos casos, la posibilidad de una trombofilia subyacente debe formar parte del diagnóstico diferencial. Presentamos el caso de una paciente joven con deficiencia de proteínas C y S como agente causal de trombosis mesentérica.

Immunophenotypic characteristics of diffuse large b-cell lymphoma and expression of C-MYC protein: single Ecuadorian center experience / Características inmunofenotípicas del linfoma difuso de células grandes B y expresión de la proteína C-MYC: experiencia en un centro de Ecuador

Abstract Background: Diffuse large B-cell lymphoma (DLBCL) makes up from 25% to 40% of all non-Hodgkin lymphomas (NHL) and is the most common histological subtype worldwide. In Ecuador, DLBCL makes up 49% of all NHL cases, but there have been no studies on the immunophenotypic classificationof DLBCL in germinal center (GC) and non-germinal center (NGC)subtypes.This study was conducted to ascertain the immunophenotypic profile of DLBCL in an Ecuadorian hospital. Methods: A total of 38 DLBCL cases from 2006 to 2015 were compiled from the Pathology Service at Metropolitan Hospital (HM) in Quito, Ecuador. Eleven of these cases failed to meet the inclusion criteria; thus, the final sample consisted of 27 cases. Manual tissue microarrays were constructed, and three immunohistochemical markers (CD10, BCL6, and MUM1) were applied according to the Hans algorithm; in addition, the expression of the c-myc protein expression was also investigated. Results: The results showed that 77.8% of cases were of the GC subtype, 11.1% were NGC, and 11.1% were unclassifiable according to the Hans algorithm. Conclusions: The most frequent DLBCL subtype was GC, with 21 cases; and 40.7% of these cases overexpressed c-myc.

Resumen Antecedentes: El linfoma difuso de células grandes B (LDCGB) constituye el 25 al 40% del total de los linfomas no Hodgkin (LNH) y es el subtipo histológico más frecuente en el mundo. En Ecuador el LDCGB corresponde al 49% del total de los casos de LNH, sin embargo no hay estudios de clasificación inmunofenotípica del LDCGB en centro germinal (CG) y no centro germinal (NCG). Este estudio se realizó para conocer el perfil inmunofenotípico del LDCGB en un hospital de Ecuador. Métodos: Se recopiló del Servicio de Patología del Hospital Metropolitano de Quito, Ecuador, un total de 38 casos de LDCGB desde el 2006 al 2015, de los cuales 11 no cumplieron con los criterios de inclusión. La muestra final fue de 27 casos. Se realizaron microarreglos tisulares manuales para la aplicación de tres marcadores de inmunohistoquímica según el algoritmo de Hans (CD10, BCL6 y MUM1) y luego se correlacionó con la sobreexpresión de la proteína c-MYC. Resultados: El 77,8% de casos fue tipo CG, 11,1% fue NCG y 11,1% fueron inclasificables según Hans. Conclusiones: El subtipo de LDCGB más frecuente fue CG con 21 casos y de estos 40,7% sobreexpresaron c-MYC.

Nefrolitotomía percutánea en pacientes con trastornos de la coagulación / Percutaneous Nephrolithotomy in Patients with Bleeding Disorders

Objetivo Reportar un caso de nefrolitotomía percutánea en paciente con deficiencia de proteína C y S. Introducción Los pacientes con déficit de proteína C y S tienen un riesgo alto de eventos tromboembólicos reportándose tasas de hasta el 6% y 8,4% respectivamente. Reporte de Caso Paciente femenina de 43 años con antecedente de deficiencia de proteína C y S, anticoagulación crónica con warfarina por trombosis venosa profunda (TVP), clínicamente con cuadro de cólico reno ureteral derecho y hematuria, la tomografía de vías urinarias mostró un cálculo coraliforme completo derecho. Fue llevada a nefrolitotomía percutánea derecha previa terapia puente con enoxaparina, el acceso percutáneo fue a través del cáliz inferior. Debido a que no fue posible acceder a los cálculos del cáliz medio y superior y que en la institución donde se realizó el procedimiento no se cuenta con nefroscopio flexible, se decidió realizar una segunda punción en cáliz superior, dejando a la paciente libre de cálculos. Se reinició la anticoagulación plena a las 12 horas del postoperatorio sin presentar sangrado asociado. Discusión Los pacientes con déficit de proteína C y S tienen un riesgo alto para eventos tromboembólicos. Kefer y col., realizaron un estudio en el que evaluaron la eficacia de la terapia puente en pacientes llevados a NLP, encontrando que la anticoagulación con warfarina puede suspenderse 5 días antes y reiniciarse 5 días después del procedimiento quirúrgico sin necesidad de terapia puente con enoxaparina. En la actualidad, las recomendaciones dadas por la Sociedad Americana de Urología, indican realizar la terapia puente mediante un grupo multidisciplinario. Resultados El déficit de proteína C y S corresponde a una entidad, con una prevalencia muy baja y condiciona el requerimiento de anticoagulantes orales de forma indefinida. Fue posible realizar una intervención quirúrgica sin complicaciones hemorrágicas ni tromboembólicas con el uso de terapia puente prequirúrgica.

Objective To report a case of percutaneous nephrolithotomy in patients with protein C and S deficiency. Introduction Patients with protein C and S deficiency have a high risk of thromboembolic events reporting rates of 6% and 8.4%, respectively. Case Report A 43-year-old female patient with a history of protein C and S deficiency with chronic warfarin anticoagulation for deep venous thrombosis (DVT). CT scan with full right staghorn calculi. Enoxaparin was administered bridge therapy. She was taken to right percutaneous nephrolithotomy, access was through the lower calyx. Because it was not possible to access the calculus of the middle and upper calyx it was necessary to perform a second puncture in the upper calyx, leaving the patient free of calculus. Full anticoagulation was resumed at 12 hours postoperatively without associated bleeding. Discussion Patients with protein C and S deficits are at high risk for thromboembolic events. Kefer et al. conducted a study evaluating the efficacy of bridge therapy in patients on NLP, finding that warfarin anticoagulation can be discontinued 5 days earlier and restarted 5 days after the surgical procedure without the need for enoxaparin bridging therapy. Results The protein C and S deficiency corresponds to an entity, with a very low prevalence and conditions the requirement of oral anticoagulants indefinitely. It was possible to perform a surgical procedure without hemorrhagic or thromboembolic complications.

A lung image reconstruction from computed radiography images as a tool to tuberculosis treatment control

Background: Tuberculosis (TB) is an infectious lung disease with high worldwide incidence that severely compromises the quality of life in affected individuals. Clinical tests are currently employed to monitor pulmonary status and treatment progression. The present study aimed to apply a three-dimensional (3D) reconstruction method based on chest radiography to quantify lung-involvement volume of TB acute-phase patients before and after treatment. In addition, these results were compared with indices from conventional clinical exams to show the coincidence level. Methods: A 3D lung reconstruction method using patient chest radiography was applied to quantify lung-involvement volume using retrospective examinations of 50 patients who were diagnosed with pulmonary TB and treated with two different drugs schemes. Twenty-five patients were treated with Scheme I (rifampicin, isoniazid, and pyrazinamide), whereas twenty-five patients were treated with Scheme II (rifampicin, isoniazid, pyrazinamide, and ethambutol). Acute-phase reaction: Serum exams included C-reactive protein levels, erythrocyte sedimentation rate, and albumin levels. Pulmonary function was tested posttreatment. Results: We found strong agreement between lung involvement and serum indices pre- and posttreatment. Comparison of the functional severity degree with lung involvement based on 3D image quantification for both treatment schemes found a high correlation. Conclusions: The present 3D reconstruction method produced a satisfactory agreement with the acute-phase reaction, most notably a higher significance level with the C-reactive protein. We also found a quite reasonable coincidence between the 3D reconstruction method and the degree of functional lung impairment posttreatment. The performance of the quantification method was satisfactory when comparing the two treatment schemes. Thus, the 3D reconstruction quantification method may be useful tools for monitoring TB treatment. The association with serum indices are not only inexpensive and sensitive but also may be incorporated into the assessment of patients during TB treatment.(AU)

Diverse characters of Brennan’s paw incision model regarding certain parameters in the rat / 대한통증학회지

BACKGROUND: Brennan’s rodent paw incision model has been extensively used for understanding mechanisms underlying postoperative pain in humans. However, alterations of physiological parameters like blood pressure and heart rate, or even feeding and drinking patterns after the incision have not been documented as yet. Moreover, though eicosanoids like prostaglandins and leukotrienes contribute to inflammation, tissue levels of these inflammatory mediators have never been studied. This work further investigates the antinociceptive effect of protein C after intra-wound administration. METHODS: Separate groups of Sprague–Dawley rats were used for quantitation of cyclooxygenase (COX) activity and leukotriene B4 level by enzyme-linked immunosorbent assay, as well as estimation of cardiovascular parameters and feeding and drinking behavior after paw incision. In the next part, rats were subjected to incision and 10 μg of protein C was locally administered by a micropipette. Both evoked and non-evoked pain parameters were then estimated. RESULTS: COX, particularly COX-2 activity and leukotriene B4 levels increased after incision. Hemodynamic parameters were normal. Feeding and drinking were affected on days 1 and 3, and on day 1, respectively. Protein C attenuated non-evoked pain behavior alone up to day 2. CONCLUSIONS: Based upon current observations, Brennan’s rodent paw incision model appears to exhibit a prolonged period of nociception similar to that after surgery, with minimal interference of physiological parameters. Protein C, which is likely converted to activated protein C in the wound, attenuated the guarding score, which probably represents pain at rest after surgery in humans.

Alterações da proteína C reativa e fator reumatoide em cães naturalmente infectados por Leishmania spp / Changes in C-reactive protein and rheumatoid factor in dogs naturally infected by Leishmania spp

A leishmaniose visceral canina é uma zoonose considerada doença tropical de prioridade. A leishmaniose afeta vários sistemas do corpo dos cães, incluindo vísceras e pele. A proteína C reativa (PCR) e o fator reumatoide (FR) são exames realizados na medicina para detecção de inflamação e artrites em seres humanos, no entanto, há poucos trabalhos voltados para cães com leishmaniose que demonstrem as alterações ocorridas na PCR e FR. Este trabalho teve como objetivo demonstrar as alterações de PCR e FR e sua correlação com a hiperproteinemia e hiperalbuminemia, além da compararação com o desvio a esquerda presente no exame hematológico. O trabalho foi realizado no Hospital Veterinário do Centro Universitário da Grande Dourados/MS e Centro de Controle de Zoonoses, no qual foram avaliados 34 cães, de diversar raças e idade e submetidos a colheita de sangue venosa para realização de exames em imuno-látex, bioquímica sérica e hemograma, em cães naturalmente infectados por Leishmania spp. Foram utilizados somente cães positivos ao teste rápido DPP® para leishmaniose, juntamente com resultado positivo no exame parasitológico, depois de diagnosticados foram realizados exames hematológicos e bioquímicos. Quando realizado o teste para quantificação de FR em soro sanguíneo, para os 34 animais estudados, foi observado positividade em apenas 1 animal, enquanto que os cães foram positivos para a PCR em 38,23% dos casos estudados. Em casos de animais com leishmaniose é possível estabelecer níveis inflamatórios precocemente, enquanto que o FR demonstrou não ser um bom marcador para animais soropositivos para a doença.(AU)

Canine visceral leishmaniasis is a zoonosis considered a priority tropical disease. The disease affects various body systems of dogs, including viscera and skin. C-reactive protein (CRP) and rheumatoid factor (RF) are tests performed in medicine for the detection of inflammation and arthritis in humans, however, there are few studies aimed at dogs with leishmaniasis that demonstrate changes in CRP and RF. This work aimed to demonstrate the changes of CRP and RF and its correlation with hyperproteinemia and hyperalbuminemia, in addition to the comparison with the left deviation present in the hematological examination. The work was carried out at the Veterinary Hospital of the University Center of Grande Dourados/MS and Zoonoses Control Center, in which 34 dogs of different breeds and ages were submitted to venous blood collection for immuno-latex exams, Biochemistry and blood count in dogs naturally infected with Leishmania spp. Only dogs to the DPP® rapid test for leishmaniasis were used, together with a positive result in parasitological examination, after hematological and biochemical tests were performed. When the test for the quantification of FR in serum was performed, for the 34 animals studied, positivity was observed in only 1 animal, while the dogs were PCR positive in 38.23% of the cases studied. In cases of animals with leishmaniasis it is possible to establish inflammatory levels early, whereas the FR showed not to be a good marker for animals seropositive for the disease.(AU)

Pro-inflammatory Cytokines, Biomarkers, Genetics and the Immune System: A Mechanistic Approach of Depression and Psoriasis / Citocinas proinflamatorias, biomarcadores, genética y sistema inmunológico: un enfoque mecanicista de la depresión y la psoriasis

ABSTRACT Objective: To highlight the inflammatory and immunological mechanisms involved in depression and psoriasis. Methods: A comprehensive literature search was performed in various databases, in total 145 studies were selected. Results: Depression and psoriasis have an association. Immune mechanisms -the actions of tumor necrosis factor-a, interleukin 1 (IL-1), IL-2, IL-10, IL-22, IL-17, interferon-7, IL-1ß, prostaglandin E2, C-reactive protein, IL-6, and IL-8 etc.-, and some genetic changes are involved. Conclusions: A possible bidirectional relationship of psoriasis and major depression exists; i.e. the depression leads to psoriasis, and psoriasis leads to depression. We recommend more studies in the future to get a deeper and better understanding about this relationship.

RESUMEN Objetivo: Poner de relieve los mecanismos inflamatorios e inmunológicos involucrados en la depresión y la psoriasis. Métodos: Se realizó en varias bases de datos una búsqueda bibliográfica completa; en total se incluyeron 145 estudios. Resultados: Hay asociación entre depresión y psoriasis y están involucrados mecanismos inmunitarios -las acciones del factor de necrosis tumoral alfa, las interleucinas (IL) 1, 2, 10, 22 y 17, el interferón gamma, la IL-1ß, la prostaglandina E2, la proteína C reactiva, la IL-6 y la IL-8, etc. - y algunos cambios genéticos. Conclusiones: Hay una posible relación bidireccional entre psoriasis y depresión, es decir, la depresión lleva a psoriasis y la psoriasis lleva a depresión. Se recomiendan más estudios en el futuro para obtener una comprensión más profunda y mejor sobre esta relación.

Trastornos asociados y factores de riesgo aterogénicos en escolares y adolescentes obesos / Associated disorders and atherogenic risk factors in obese school children and adolescents

Introducción: la obesidad en la edad pediátrica predispone a la enfermedad aterosclerótica precoz en la adultez, independientemente del peso futuro. Objetivo: caracterizar el patrón antropométrico, morbilidad asociada y factores de riesgo aterogénico en obesos. Métodos: se realizó un estudio descriptivo y prospectivo con 62 pacientes obesos atendidos en la consulta de Endocrinología del Hospital Pediátrico William Soler , entre enero y diciembre de 2016. Fueron analizadas variables demográficas, antropométricas y de riesgo aterogénico por medio de prevalencia (por ciento) y pruebas de hipótesis (significativo: p< 0,05 o coeficiente Eta 1). Resultados: la obesidad fue significativa en escolares y el sexo masculino (p= 0,000). La obesidad abdominal (n= 48/77,4 por ciento) predominó en el sexo femenino (n= 20/90,9 por ciento), y entre los 6 y 10 años (n= 14/63,6 por ciento). La obesidad generalizada tuvo diagnóstico significativamente superior que la obesidad abdominal (p= 0,001) y fue independiente del sexo (Eta= 0,049) y la edad (p= 0,066). La prevalencia de acantosis nigricans (n= 39/62,9 por ciento) fue significativa (p= 0,042). Las alteraciones humorales, clínicas y ecográficas analizadas se manifestaron por encima de 70 por ciento en presencia de obesidad abdominal y la generalizada, ambas asociadas con elevación de proteína C reactiva (p< 0,05), y a su vez, la generalizada con remodelación ventricular izquierda (p= 0,049). Conclusión: la obesidad es distintiva de los escolares y del sexo masculino, pero la de tipo abdominal caracteriza a las niñas; existe una baja prevalencia de factores de riesgo aterogénico en los pacientes estudiados. La adiposidad abdominal y la generalizada implican un incremento de la proteína C reactiva plasmática; se evidencia el remodelado ventricular izquierdo cuando existe obesidad generalizada(AU)

Introduction: obesity in the pediatric age predisposes to early atherosclerotic disease in adulthood, regardless of future weight. Objective: to characterize the anthropometric pattern, associated morbidity and atherogenic risk factors in obese patients. Methods: a descriptive and prospective study was carried out with 62 obese patients attended in the Endocrinology clinic of William Soler Pediatric Hospital, from January to December 2016. Demographic, anthropometric and atherogenic risk variables were analyzed by means of prevalence (percent) and hypothesis testing (significant: p< 0.05 or Eta coefficient 1). Results: obesity was significant in schoolchildren and male sex (p= 0.000). Abdominal obesity (n= 48/77.4 percent) predominated in females (n= 20/90.9 percent), and among 6 and 10 years old (n= 14/63.6 percent). Generalized obesity had a significantly higher diagnosis than abdominal obesity (p = 0.001) and didn´t have relation with sex (Eta= 0.049) and age (p= 0.066). The prevalence of acanthosis nigricans (n= 39 / 62.9 percent) was significant (p= 0.042). The humoral, clinical and ultrasonographic alterations analyzed were above 70 percent in the presence of abdominal and generalized obesity, both associated with elevated C-reactive protein (p< 0.05), and at the same time, the generalized with left ventricular remodeling (p= 0.049). Conclusions: obesity is distinctive among school children and males, but abdominal type characterizes girls. There is a low prevalence of atherogenic risk factors in the patients studied. Abdominal and generalized adiposity imply an increase in plasma C-reactive protein. Left ventricular remodeling is evidenced when there is generalized obesity(AU)