Cardiovascular disease risk prediction in scleroderma

SUMMARY OBJECTIVE: Cardiovascular disease risk prediction in scleroderma is important. In this study of scleroderma patients, the aim was to investigate the relationship between cardiac myosin-binding protein-C, sensitive troponin T, and trimethylamine N-oxide and cardiovascular disease risk with the Systematic COronary Risk Evaluation 2 model of the European Society of Cardiology. METHODS: Systematic COronary Risk Evaluation 2 risk groups of 38 healthy controls and 52 women with scleroderma were evaluated. Cardiac myosin-binding protein-C, sensitive troponin T, and trimethylamine N-oxide levels were analyzed with commercial ELISA kits. RESULTS: In scleroderma patients, cardiac myosin-binding protein-C and trimethylamine N-oxide levels were higher than healthy controls but sensitive troponin T was not (p<0.001, p<0.001, and p=0.274, respectively). Out of 52 patients, 36 (69.2%) were at low risk, and the other 16 (30.8%) patients were at high-moderate risk with the Systematic COronary Risk Evaluation 2 model. At the optimal cutoff values, trimethylamine N-oxide could discriminate high-moderate risk with sensitivity 76%, specificity 86% and cardiac myosin-binding protein-C with sensitivity 75%, specificity 83%. Patients with high trimethylamine N-oxide levels (≥10.28 ng/mL) could predict high-moderate- Systematic COronary Risk Evaluation 2 risk 15 times higher than those with low trimethylamine N-oxide (<10.28 ng/mL) levels (odds ratio [OR]: 15.00, 95%CI 3.585-62.765, p<0.001). Similarly, high cardiac myosin-binding protein-C (≥8.29 ng/mL) levels could predict significantly higher Systematic COronary Risk Evaluation 2 risk than low cardiac myosin-binding protein-C (<8.29 ng/mL) levels (OR: 11.00, 95%CI 2.786-43.430). CONCLUSION: Noninvasive cardiovascular disease risk prediction indicators in scleroderma, cardiac myosin-binding protein-C, and trimethylamine N-oxide could be recommended to distinguish between high-moderate risk and low risk with the Systematic COronary Risk Evaluation 2 model.

Feasibility of outer membrane protein C as a protein presenting platform targeting antigen to surface of outer membrane vesicle / 中国生物制品学杂志

@#Abstract：Objective To investigate the feasibility of outer membrane protein C（OmpC）as a protein presenting platform targeting antigen to the surface of outer membrane vesicle（OMV）. Methods The recombinant expression plasmid containing ompC gene fragment and Staphylococcus aureus EsxA antigen gene（esxA gene）was constructed，transformed to competent E. coli BL21（DE3），inducedbyIPTG，andanalyzedforexpressedproductby 12%SDS⁃PAGE. Thetotalproteinofrecombinant strain OMV was analyzed by 12% SDS⁃PAGE，and the localization of fusion protein on the surface of OMV was detected by Western blot and Flow NanoAnalyzer. Results The recombinant expression plasmid containing ompC gene and esxA gene was constructed correctly as proved by sequencing. 12% SDS⁃PAGE showed that the fusion protein OmpC⁃EsxA had a relative molecular mass of about 57 000，which was consistent with the expected size，while the total protein of OMV showed multiple target protein bands，indicating that recombinant strain OMV was successfully extracted. The fusion protein OmpC⁃ EsxA on the surface of recombinant strain OMV specifically bound to mouse antibody against His⁃Tag，and OMVs labeled with fluorescent antibody were detected by Flow NanoAnalyzer. Conclusion OmpC may be used as a protein presenting plat⁃ form to locate antigen to OMV surface，which was expected to be applied in the development of antigen presentation vaccine. Keywords：Outer membrane protein C（OmpC）；Protein presentation；Outer membrane vesicle（OMV）

Inherited protein C deficiency in pregnancy: a case report / 中华围产医学杂志

This paper reported the management of a pregnant women with inherited protein C deficiency. The patient had a history of recurrent deep vein thrombosis before pregnancy and was diagnosed with inherited protein C deficiency by a pedigree-based whole exome sequencing, which revealed PROC gene mutations. She received anticoagulation treatment and was managed by a multidisciplinary team during pregnancy. No significant abnormalities were found during routine prenatal examination and a male infant was delivered vaginally at 38 +2 gestational weeks. No postpartum hemorrhage was reported and the maternal and infant outcomes were good. The management of such patients during pregnancy mainly relied on anticoagulation therapy to avoid serious thrombotic events and ensure the safety of the mothers and fetuses.

Extra hepatic portal vein obstruction due to combined protein ‘C’ and ‘S’ deficiency - A case report

Extra-hepatic portal vein obstruction (EHPVO) is an important cause of non-cirrhotic portal hypertension, in Third World countries like India. In this disorder, it results in obstruction and cavernomatous transformation of portal vein with or without the involvement of intra-hepatic portal vein, splenic vein, or superior mesenteric vein resulting in portal hypertension and esophagogastric varices. Extensive collateral circulation develops, involving paracholecystic, paracholedochal and pancreaticoduodenal veins which results in formation of ectopic varices, and portal biliopathy. Besides variceal bleeding, patients may have symptoms of portal biliopathy, hypersplenism, and growth retardation. Although the liver may appear normal, functional compromise develops in the long term. Patients with extra-hepatic portal vein obstruction are usually young and belong to India and other Asian countries. The variceal bleeding in EHPVO can be managed by endoscopic obliteration of varices, or by portosystemic shunt surgery. In this case report, we present a case of 15 year old male, with extra-hepatic portal vein obstruction due to combined deficiency of Protein C and Protein S recanalized by short-term low molecular heparin plus oral Rivaroxaban therapy

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)

Correlation between protein C -1641A/-1654C haplotype and coagulation disorder in sepsis / 中华急诊医学杂志

Objective:To investigate the correlation between protein C -1641A/-1654C haplotype and coagulation disorder in Chinese Han septic patients.Methods:The genotypes of protein C gene -1641A>G (rs1799809) and -1654C>T (RS1799808) in septic patients were detected by direct sequencing, and their haplotypes were analyzed and divided into two groups according to the haplotype, -1641A/-1654C (AC) carriers and non-AC haplotype carriers. At the same time, unpaired t test or Mann-Whitney U test was used to compare the differences in coagulation/fibrinolytic parameters, including partial activated thrombin time, prothrombin time, internationally standardized ratio of prothrombin time, thrombin time, fibrinogen and D-dimer levels, as well as APC levels between the two groups. Results:A total of 174 septic patients were included in this study, including 60 AC haplotype carriers and 114 non-AC haplotype carriers. Compared with non-AC haplotype carriers, AC haplotype carriers had significantly lower platelet counts, significantly longer partial activated thrombin time, and significantly decreased activated protein C levels. Other coagulation/fibrinolytic parameters including prothrombin time, internationally standardized ratio of prothrombin time, thrombin time, fibrinogen and D-dimer were not significantly different between the two groups.Conclusions:In this study, the protein C-1641A/-1654C haplotype was found to lead to decreased circulating activated protein C levels decreased platelet counts, and prolonged partial activated thrombin time in septic patients. These results suggest that the protein C-1641A/-1654C haplotype may directly affect the APC level and consequently influence the coagulation disorder of sepsis.

Neonatal-onset protein C deficiency: case report and literature review / 中国新生儿科杂志

Objective:To study the clinical features, diagnosis, treatment and genetic characteristics of neonatal-onset protein C deficiency (PCD).Methods:The clinical data of a newborn patient with severe PCD admitted to our neonatal department was reviewed. Databases including CNKI, Wanfang Database, CMB, VIP database, PubMed, Embase and SCI database were searched using" infantile", " neonate ", "newborn", "protein C deficiency" and "purpura fulminans" as key words. Published cases of PCD were analyzed.Results:The patient was a full-term female infant who developed multiple symptoms within 2 days after birth. The symptoms included thrombocytopenia, intracranial hemorrhage, purpura fulminans (PF), disseminated intravascular coagulation (DIC), celiac hemorrhage, hypertension, portal and iliac vein thrombosis, purulent meningitis and retinal detachment. Protein C activity was less than 10%. Genetic tests showed compound heterozygous mutations c.314G>T (p.c105f) of paternal origin and c.1218G>A (p.m406i) of maternal origin in PROC gene. According to ACMG guidelines, the mutations were strongly suspected pathogenic variants and consistent with an autosomal recessive (AR) inheritance pattern. The patient was discharged after 6 weeks of treatment at parents' request of withdrawal. A total of 25 articles on 29 patients with relatively complete clinical data were retrieved, including 18 males and 11 females. 4 patients were preterm and 25 full-term. 28 patients showed symptoms within 7 days after birth. The common clinical features were cutaneous PF and splanchnic thrombi. 22 cases documented protein C activity and ranged from 0 to 25%. 16 patients had PROC gene abnormalities and compound heterozygous mutations were found in 10 patients. Among the 22 patients with prognostic data, 11 died (9 within 3 months after birth), the remaining survivors suffered from sequelae including severe intellectual motor development disorder, epilepsy and blindness.Conclusions:The main clinical manifestations of neonatal-onset PCD include PF, DIC, multi-organ hemorrhage and thrombus. The disease is acute and severe, with rapid progression, poor prognosis and high fatality rate. Protein C activity and PROC gene testing may help establish the diagnosis.

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.

Trombosis múltiple con presentacion inusual. reporte de caso / Multiple thrombosis with unusual presentation. case report

RESUMEN: Presentamos el caso clínico de un varón de 58 años de edad, con trombosis por déficit de Proteína C y S, tras descartar proceso secundario, inmunológico y oncológico.

ABSTRACT: We present the clinical case of a 58-year-old man with protein C and S deficiency thrombosis, after ruling out secondary, immunological and oncological processes.

Analysis of the pedigree of a child with interstitial lung disease caused by a novel mutation of p. K114N in SFTPC gene / 中国小儿急救医学

Objective:To analyze the clinical and chest CT features in a family with interstitial lung disease(ILD), and assess the probable causative gene mutations for the family.Methods:In order to identify the etiology of the proband′s ILD, the pedigree was investigated.The clinical data of five proband′s pedigree members were collected, and the chest HRCT examination was performed on four proband′s pedigree members with respiratory symptoms.The human whole exon sequencing was performed on the proband′s blood samples, then its deleterious effects were assessed.Subsequently, the strong pathogenic mutation was validated by Sanger sequencing.Results:According to the family survey, there were five patients with ILD in the family, including three males and two females.One of them died.The surfactant protein C(SFTPC)gene(exon4, c.342G>T, p.K114N)was found in all four surviving patients.The mutation was considered to be originated from the father of the proband, and the pathogenic mutation was considered, which was not included in the databases and was a noval mutation.In addition, the clinical manifestations of different patients in the family were significantly different.Conclusion:The novel mutation of p. k114n in SFTPC gene can lead to ILD in children, and the mutation has incomplete exons in family members.Chest CT and whole exon sequencing play an important role in the diagnosis of ILD in children.

Trombosis y su relación con la deficiencia de proteínas C y S / Thrombosis and its relationship to protein C and S deficiency

La trombosis se puede definir como un trastorno vascular que se presenta cuando se desarrolla un trombo que bloquea de forma total o parcial el interior de un vaso sanguíneo, ya sea una vena o una arteria. La trombofilia define a una alteración de la hemostasia que predispone al desarrollo de trombosis; sin embargo, la presencia de una trombofilia no implica necesariamente la aparición de un evento trombótico. La deficiencia de los inhibidores fisiológicos, como las proteínas C y S, constituyen factores de riesgo hereditarios y adquiridos que favorecen al desarrollo de trombosis. Se determinó la incidencia de deficiencia de estas proteínas de la coagulación en pacientes con historia obstétrica adversa, eventos de trombosis y otros eventos asociados. Se realizó un estudio longitudinal prospectivo en el período comprendido del 2011 al 2018, en un grupo de pacientes remitidos al Instituto de Hematología e Inmunología, a los que se les realizó la medición de los niveles plasmáticos de las proteínas C y S. En 133 pacientes (52,17 por ciento) se detectó deficiencia de proteína C (n=50), proteína S (n=66) o ambas (n=17). Las principales causas de realización de estos estudios fueron la historia obstétrica adversa y los eventos trombóticos y coincidieron con los eventos clínicos donde predominó alguna deficiencia. La deficiencia de proteína S tuvo mayor incidencia(AU)

Thrombosis is a vascular disorder appearing when a thrombus totally or partially blocks the inside of a blood vessel, be it a vein or an artery. Thrombophilia is a hemostatic alteration leading to thrombosis. However, the presence of thrombophilia does not necessarily imply the appearance of a thrombotic event. Deficiency in physiological inhibitors such as proteins C and S is a hereditary or acquired risk factor fostering thrombosis. Determination was made of the incidence of deficiency in these coagulation proteins in patients with an adverse obstetric history, thrombotic events and other associated disorders. A prospective longitudinal study was conducted in the period 2011-2018 of a group of patients referred to the Institute of Hematology and Immunology, who underwent measurement of their plasma levels of proteins C and S. A total 133 patients (52.17 percent) were found to be deficient in protein C (n=50), protein S (n=66) or both (n=17). The main reasons for the conduct of these studies were an adverse obstetric history and thrombotic events, which coincided with clinical disorders in which some sort of deficiency prevailed. Protein S deficiency was the most common(AU)

Predictive values of C-reactive protein/albumin ratio in new-onset atrial fibrillation after coronary artery bypass grafting

SUMMARY OBJECTIVE This study aimed to investigate the predictive value of the newly defined C-Reactive Protein (CRP)/Albumin Ratio (CAR) in determining the development of atrial fibrillation (AF) in comparison with other inflammatory markers, such as Neutrophil/Lymphocyte (N/L) Ratio and Platelet/Lymphocyte (P/L) Ratio, in patients undergoing Coronary Artery Bypass Grafting (CABG) surgery. METHODS The population of this observational study consisted of 415 patients undergoing CABG. The study cohort was subdivided into two groups based on the development of AF. Complete blood counts, serum CRP, and serum albumin levels were evaluated before the CABG. The CAR, N/L, and P/L ratios of all the patients were calculated. Predictors of postoperative AF were determined by multiple logistic regression analysis (MLRA). RESULTS During follow-up, 136 patients (32.8%) developed postoperative AF. With MLRA, independent risk factors for postoperative AF were determined as follows: fasting glucose level (OR: 1.01; 95 % CI: 1.00-1.01, P <0.001), age (OR: 1.12; 95 % CI: 1.07-1.17, P <0.001), left ventricle ejection fraction (OR: 0.90; 95 % CI: 0.87-0.94, P <0.001), male gender (OR: 3.32; 95 % CI: 1.39-7.90, P = 0.007), 24-hour drainage amount (OR: 1.004; 95 % CI: 1.002-1.005, P <0.001), and CAR (OR: 1.82; 95 % CI: 1.53-2.16, P <0.001). Receiver Operating Characteristic curve analysis showed that CAR (C-statistic: 0.75; 95% CI: 0.71-0.79, p< 0.001) was a significant predictor of AF. CONCLUSION Novel inflammatory marker CAR can be used as a reliable marker to predict the development of AF following CABG.

RESUMO OBJETIVO Este estudo teve como objetivo investigar o valor preditivo da recém-definida relação entre Proteína C-Reativa (PCR) e Albumina (CAR) na determinação do desenvolvimento de Fibrilação Atrial (FA) em comparação com outros marcadores inflamatórios, como proporção de Neutrófilos para Linfócitos (N/L) e relação Plaquetas/Linfócitos (P/L) em pacientes submetidos à Cirurgia de Revascularização do Miocárdio (CRM). MÉTODOS A população deste estudo observacional foi composta por 415 pacientes submetidos à cirurgia de revascularização do miocárdio. A coorte do estudo foi subdividida em dois grupos de acordo com o desenvolvimento da FA. Contagens sanguíneas completas, PCR sérica e albumina sérica foram obtidas antes da CRM. Os valores de CAR, relação N/L e relação P/L foram calculados. Os preditores de FA pós-operatória foram determinados por análise de regressão logística múltipla. RESULTADOS Durante o acompanhamento, 136 pacientes (32,8%) desenvolveram FA pós-operatória. Com análise de regressão logística múltipla, foram determinados os fatores de risco para FA pós-operatória: glicemia de jejum (OR: 1,01; IC 95%: 1,00-1,01, p<0,001), idade (OR: 1,12; IC 95%: 1,07-1,17, p<0,001), fração de ejeção do ventrículo esquerdo (OR: 0,90; IC 95%: 0,87-0,94, p<0,001), sexo masculino (OR: 3,32; IC 95%: 1,39-7,90, p=0,007), quantidade de drenagem de 24 horas (OR: 1,004; IC 95%: 1,002-1,005, p<0,001), CAR (OR: 1,82; IC 95%: 1,53-2,16, p<0,001). A análise da curva de características operacionais do receptor mostrou que o CAR (estatística C: 0,75; IC 95%: 0,71-0,79, p<0,001) foi um preditor significativo de FA. CONCLUSÃO O novo marcador inflamatório CAR é confiável para prever o desenvolvimento de FA após a operação de revascularização miocárdica.

Relationship between c-reactive protein/albumin ratio and new-onset atrial fibrillation after coronary artery bypass grafting

SUMMARY OBJECTIVE This study aimed to investigate the predictive value of the newly defined C-Reactive Protein (CRP)/Albumin Ratio (CAR) in determining the development of atrial fibrillation (AF) in comparison with other inflammatory markers, such as Neutrophil/Lymphocyte (N/L) Ratio and Platelet/Lymphocyte (P/L) Ratio, in patients undergoing Coronary Artery Bypass Grafting (CABG) surgery. METHODS The population of this observational study consisted of 415 patients undergoing CABG. The study cohort was subdivided into two groups based on the development of AF. Complete blood counts, serum CRP, and serum albumin levels were evaluated before the CABG. The CAR, N/L, and P/L ratios of all the patients were calculated. Predictors of postoperative AF were determined by multiple logistic regression analysis (MLRA). RESULTS During follow-up, 136 patients (32.8%) developed postoperative AF. With MLRA, independent risk factors for postoperative AF were determined as follows: fasting glucose level (OR: 1.01; 95 % CI: 1.00-1.01, P <0.001), age (OR: 1.12; 95 % CI: 1.07-1.17, P <0.001), left ventricle ejection fraction (OR: 0.90; 95 % CI: 0.87-0.94, P <0.001), male gender (OR: 3.32; 95 % CI: 1.39-7.90, P = 0.007), 24-hour drainage amount (OR: 1.004; 95 % CI: 1.002-1.005, P <0.001), and CAR (OR: 1.82; 95 % CI: 1.53-2.16, P <0.001). Receiver Operating Characteristic curve analysis showed that CAR (C-statistic: 0.75; 95% CI: 0.71-0.79, p< 0.001) was a significant predictor of AF. CONCLUSION Novel inflammatory marker CAR can be used as a reliable marker to predict the development of AF following CABG.

RESUMO OBJETIVO Este estudo teve como objetivo investigar o valor preditivo da recém-definida relação entre Proteína C-Reativa (PCR) e Albumina (CAR) na determinação do desenvolvimento de Fibrilação Atrial (FA) em comparação com outros marcadores inflamatórios, como proporção de Neutrófilos para Linfócitos (N/L) e relação Plaquetas/Linfócitos (P/L) em pacientes submetidos à Cirurgia de Revascularização do Miocárdio (CRM). MÉTODOS A população deste estudo observacional foi composta por 415 pacientes submetidos à cirurgia de revascularização do miocárdio. A coorte do estudo foi subdividida em dois grupos de acordo com o desenvolvimento da FA. Contagens sanguíneas completas, PCR sérica e albumina sérica foram obtidas antes da CRM. Os valores de CAR, relação N/L e relação P/L foram calculados. Os preditores de FA pós-operatória foram determinados por análise de regressão logística múltipla. RESULTADOS Durante o acompanhamento, 136 pacientes (32,8%) desenvolveram FA pós-operatória. Com análise de regressão logística múltipla, foram determinados os fatores de risco para FA pós-operatória: glicemia de jejum (OR: 1,01; IC 95%: 1,00-1,01, p<0,001), idade (OR: 1,12; IC 95%: 1,07-1,17, p<0,001), fração de ejeção do ventrículo esquerdo (OR: 0,90; IC 95%: 0,87-0,94, p<0,001), sexo masculino (OR: 3,32; IC 95%: 1,39-7,90, p=0,007), quantidade de drenagem de 24 horas (OR: 1,004; IC 95%: 1,002-1,005, p<0,001), CAR (OR: 1,82; IC 95%: 1,53-2,16, p<0,001). A análise da curva de características operacionais do receptor mostrou que o CAR (estatística C: 0,75; IC 95%: 0,71-0,79, p<0,001) foi um preditor significativo de FA. CONCLUSÃO O novo marcador inflamatório CAR é confiável para prever o desenvolvimento de FA após a operação de revascularização miocárdica.

Management and therapeutic implications of combined protein C and S deficiency in pregnancy: a case report

The pregnancy is an immunocompromised state. Thus, autoimmune diseases may affect pregnancy and get worsen during pregnancy. Here authors discuss a rare autoimmune thrombophilia disorder, protein C and S deficiency which may cause recurrent pregnancy losses by affecting haemostatic mechanisms in the body. This patient with recurrent pregnancy loss when evaluated extensively was found to have combined inherited protein C and S deficiency. It was successfully managed with thromboprophylaxis therapy, which resulted in the delivery of healthy baby. Long term anticoagulant prophylaxis should be considered weighing the risk of bleeding to thrombotic recurrence in such cases. In conclusion, combined protein C and S deficiency and that too presenting as recurrent pregnancy loss is very rare. Thrombophilia screening should be considered in cases of recurrent pregnancy losses. Adequate and appropriate thromboprophylaxis is an important part of the management of pregnant women with inherited thrombophilia.

Risk factors including prothrombotic work up in young ischemic stroke Indian patients

Background: Stroke in young poses a major health problem. Various Indian studies have shown the incidence of stroke to be 10-15%. Cerebral venous thrombosis and rheumatic heart disease are the leading causes of stroke in the young in India. Thrombophilic factors have been implicated in 4-8% of the young strokes worldwide. Protein C deficiency is the most common thrombophilia marker followed by a deficiency of protein S, Factor V Leiden mutation, and antithrombin (AT) deficiency. Aims and objectives was the study of stroke in young is important for various reasons. The etiology and risk factors are more diverse and different as compared to the elderly. Therefore, these may indicate separate therapeutic approaches. The aim is to study the profile of ischemic stroke cases among the young.Methods: The study was carried out at a tertiary care defence hospital between December 2018 to December 2019. All cases of fresh ischemic stroke who were more than 15 and less than 45 years of age were included. Following clinical evaluation, patients underwent complete haemogram, blood sugar levels, lipid profile and other metabolic parameters. All patients were subjected to chest radiography, 12 lead ECG, and 2D echocardiography, Non-contrast CT head and MRI brain. Prothrombotic work up was also done.Results: A total of 41 patients (12.69%) presented with ischemic stroke before 45 years of age. Out of these 10 (24%) were females and 31 (76%) were male. None of the women smoked or consumed alcohol. Among the males, 19 (47%) smoked more than 10 cigarettes or bidis per day and 9 (22%) were moderate-to-heavy drinkers of alcohol. Hypertension was present in 7 (18%) and diabetes mellitus in 3 (7%) patients. Serum cholesterol was elevated in 7 (18%) patients and triglycerides in 17 (42%). Protein S deficiency was found in 28.8% patients, while protein C deficiency was detected in 21% patients and antithrombin III deficiency in 12% patients.Conclusions: Although traditional risk factors, such as hypertension, diabetes, and smoking, are associated with stroke in both elderly and young, this study shows that other modifiable risk factors such as alcohol consumption were also prevalent. The most common etiological cause was found to be venous infarction followed by cardio embolic cause. Deficiency of Protein S was the most common prothrombotic defect followed by deficiency of Protein C.

Incidence of thrombophilia in patients with recurrent pregnancy loss

Background: Approximately 1-3% of women of reproductive age suffer from recurrent pregnancy loss. Objective of this study was to evaluate the association between recurrent pregnancy loss and thrombophilia.Methods: This is a descriptive study, involving retrospective analysis of patients with recurrent pregnancy losses. Patients with recurrent pregnancy loss in whom associated morbidity factors were excluded underwent screening for both acquired and inherited thrombophilia.Results: A total of 20 patients were screened for acquired and inherited thrombophilia with recurrent pregnancy loss. Thrombophilia was diagnosed in 70% cases. Out of which, anticardiolipin antibodies was found positive in 57% of patients, protein C 7% and protein S deficiency was observed in 35% cases.Conclusions: Thrombophilias are associated with recurrent pregnancy loss. Patients in whom other associated morbid factors are excluded, should be offered screening for thrombophilia. Multidisciplinary management involving hematologist is vital for management.

KLF5 suppresses TRAIL-induced cell apoptosis in PC-3 prostate cancer cells / 西安交通大学学报(医学版)

Objective: To explore the possibility of promoting tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis in prostate cancer PC-3 cell by inhibiting Krüppel-like factor 5 (KLF5). Methods: MTT assay, flow cytometry, Western blot assay and qRT-PCR assay were deployed to detect the cell viability, apoptosis and apoptotic markers in KLF5-inhibited and TRAIL-induced PC-3 cells. Results: After KLF5 was inhibited in TRAIL-induced PC-3 cells, cell viability reduced, apoptosis enhanced, the expressions of DR4 and DR5 increased while the expression of cellular fas-associated death domain-like interleukin-1β converting enzyme inhibitory protein (c-FLIP) decreased. Conclusion: Inhibiting KLF5 suppresses cell viability by promoting TRAIL-induced apoptosis in prostate cancer cell PC-3. It may be a potential means to treat hormone-insensitive prostate cancer.

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.

Recurrent abdominal and lower limb venous thrombosis due to inherent protein-C and protein-S deficiency

Protein-C and protein-S deficiency is associated with a hypercoagulable state which usually presents with recurrent venous thrombosis as a common complication. But extensive thrombosis involving all the major abdominal and lower limb veins is quite rare. Here, we report a case of a 27-year-old woman presented with engorged veins all over abdomen and chest since 20 days. Clinical examination revealed signs suggestive of portal venous hypertension with moderate splenomegaly. Protein-C and protein-S levels were found to be low. Portal venous doppler ultrasound and CT-venogram revealed chronic thrombosis of portal vein, inferior vena cava, bilateral iliac and femoral veins with extensive collaterals formation and partial thrombosis in collaterals as well.  The patient was successfully managed with anti-coagulating agent (acenocoumarol) and has been maintained on regular follow-up to avoid reoccurrence of thrombosis.

Assessment of Protein C and Protein S of Pregnancy Loss Victims

Background: The haemostatic changes that result in thrombophilia during the pregnant state have been linked to pregnancy loss. Objective: Assessment of Protein S, and Protein C assays in pregnancy loss victims in Abia State, South East, Nigeria. Materials and Methods: This was a cross-sectional study involving women in their reproductive years. Study population was stratified into 3 groups and the Protein C and Protein S concentrations measured and compared among the three groups. Results: A total of 130 apparently healthy Nigerian women of child-bearing age were enrolled in the study. The study groups consisted of 70 women who had just lost a pregnancy, 30 women with normally progressing pregnancy and 30 nonpregnant women. The protein C concentration for the pregnancy-loss subjects was significantly lower than that of the normal pregnancy at p ? 0.01 while that of Protein S showed non-significance (p > 0.05). Conclusion: Protein C deficiency is associated with increase in pregnancy loss.