Guillain-Barre syndrome after myocardial infarction: a case report and literature review.

BACKGROUND: Guillain-Barre syndrome after myocardial infarction occurs infrequently, and its occurrence following percutaneous coronary intervention is extremely rare. Due to the high mortality rate of myocardial infarction and the disability of Guillain-Barre syndrome, early identification of Guillain-Barre syndrome after myocardial infarction and early intervention can decrease the mortality rate, lead to early recovery, and provide a better outcome. CASE PRESENTATION: Herein, we reported a rare case of Guillain-Barre syndrome after myocardial infarction treated with percutaneous coronary intervention. The patient was a 75-year-old woman from China who was admitted to hospital due to sudden loss of consciousness. Electrocardiography showed acute myocardial infarction in the right ventricle and inferior and posterior walls. The patient underwent emergency percutaneous intervention of the posterior collateral artery of the right coronary artery. Soon after, her condition worsened resulting in limb weakness and numbness. Unfortunately, she continued to develop respiratory failure, and treated with intravenous immunoglobulin and ventilator-assisted breathing. A physical examination showed hypotonia of all four limbs, complete quadriplegia, bulbar palsy, dysarthria, and tendon areflexia. Serum immunoglobulin (Ig) G anti-ganglioside antibody analysis was positive with anti-GT1a antibodies (+ +), anti-GM1 antibodies ( +), anti-GM2 antibodies ( +), and anti-GM4 antibodies ( +), and he was diagnosed with Guillain-Barre syndrome after myocardial infarction. She was discharged due to poor response to treatment. The patient died two days after being discharged. CONCLUSIONS: Myocardial infarction and/or percutaneous coronary intervention may activate immune-mediated response and cause severe complications. Clinician should be alert to Guillain-Barre syndrome after myocardial infarction and/or percutaneous coronary intervention.

Multiple Mutations on α, ß and γ Domains of Streptokinase Lead to the Generation of Highly Efficient Cysteine Analogues with Promising Features.

BACKGROUND: Streptokinase, one of the most widely used thrombolytic medicines, is a favorable protein for site-specific PEGylation as it lacks any cysteine residues in its amino acid sequence; however, any changes in the protein's structure should be carefully planned to avoid undesired changes in its function. OBJECTIVES: This study aimed to design and produce novel di/tri-cysteine variants of streptokinase from previously developed cysteine analogues, Arg45, Glu263, and Arg319, as candidates for multiple site-specific PEGylation. METHODS: Using bioinformatics tools and site-directed mutagenesis, we incorporated concurrent mutations at Arg45, Glu263, and Arg319 (carried out in our previous study) to create di/tri-cysteine variants of streptokinase proteins (SK45-319cys, SK263-319cys, and SK45-263-319cys) and evaluated their kinetic activity parameters by a colorimetric method, using H-D-Val-Leu-Lys-pNA.2HCl (S2251) as substrate. RESULTS: Based on the kinetic results, SK263-319cys with 44% enzyme efficiency increment compared to wild-type SK was the superior protein in terms of activity; as well, SK45-319cys and SK45-263-319cys showed 17 and 22% activity enhancement, respectively. Docking of the mutant streptokinase proteins with µ-plasmin demonstrated that changes in intermolecular interactions caused by amino acid substitution could be the reason for activity difference. CONCLUSION: The novel mutant proteins created in this study exhibit remarkable biological activity and may be uniquely suitable for simultaneous PEGylation on two/three domains. As well, PEGylated derivates of these variants might prove to be more proficient proteins, compared to the singlecysteine analogs of streptokinase; because of their more surface coverage and increased molecular weight.

Ensayo controlado y aleatorizado del uso de Heberkinasa® en el derrame pleural paraneumónico en niños / Randomized Controlled Trial of the Use of Heberkinase® in Parapneumonic Pleural Effusion in Children

Introducción: El derrame pleural paraneumónico resulta la complicación más frecuente de la neumonía bacteriana, de manejo complejo y muchas veces quirúrgico. No existen publicaciones en Cuba provenientes de ensayos clínicos controlados y aleatorizados ni del uso de la estreptoquinasa recombinante (Heberkinasa®) en el derrame pleural. Objetivo: Evaluar la eficacia y la seguridad de la Heberkinasa® en el tratamiento del derrame pleural paraneumónico complicado complejo y el empiema en niños. Métodos: Ensayo clínico fase III, abierto, aleatorizado (2:1), en grupos paralelos y controlado. Se concluyó la inclusión prevista de 48 niños (1-18 años de edad), que cumplieron los criterios de selección. Los progenitores otorgaron el consentimiento informado. Los pacientes se distribuyeron en dos grupos: I- experimental: terapia estándar y administración intrapleural diaria de 200 000 UI de Heberkinasa® durante 3-5 días y II-control: tratamiento estándar. Las variables principales: necesidad de cirugía y la estadía hospitalaria. Se evaluaron los eventos adversos. Resultados: Ningún paciente del grupo I-experimental requirió cirugía, a diferencia del grupo II-control en el que 37,5 por ciento necesitó cirugía video-toracoscópica, con diferencia altamente significativa. Se redujo la estadía hospitalaria (en cuatro días), las complicaciones intratorácicas y las infecciones asociadas a la asistencia sanitaria en el grupo que recibió Heberkinasa®. No se presentaron eventos adversos graves atribuibles al producto. Conclusiones: La Heberkinasa® en el derrame pleural paraneumónico complicado complejo y empiema resultó eficaz y segura para la evacuación del foco séptico, con reducción de la necesidad de tratamiento quirúrgico, de la estadía hospitalaria y de las complicaciones, sin eventos adversos relacionados con su administración(AU)

Introduction: Paraneumonic pleural effusion is the most frequent complication of bacterial pneumonia, with complex and often surgical management. There are no publications in Cuba from randomized controlled clinical trials or the use of recombinant streptokinase (Heberkinase®) in pleural effusion. Objective: To evaluate the efficacy and safety of Heberkinase® in the treatment of complex complicated parapneumonic pleural effusion and empyema in children. Methods: Phase III, open-label, randomized (2:1), parallel-group, controlled clinical trial. The planned inclusion of 48 children (1-18 years of age), who met the selection criteria, was completed. Parents gave informed consent. The patients were divided into two groups: I-experimental: standard therapy and daily intrapleural administration of 200,000 IU of Heberkinase® for 3-5 days; and II-control: standard treatment. The main variables: need for surgery and hospital stay. Adverse events were evaluated. Results: No patient in group I-experimental required surgery, unlike group II-control in which 37.5 percent required video-assisted thoracoscopic surgery, with a highly significant difference. Hospital stay (to 4 days), intrathoracic complications and infections associated to healthcare in the group that received Heberkinase® was reduced. No serious adverse events attributable to the product occurred. Conclusions: Heberkinase® in complex complicated parapneumonic pleural effusion and empyema was effective and safe for the draining of the septic focus, with reduction of the need for surgical treatment, hospital stay and complications, with no adverse events related to its administration(AU)

Factores pronósticos de fallo de trombólisis en pacientes con diagnóstico de infarto agudo de miocardio / Prognostic factors of thrombolytic failure in patients diagnosed with acute myocardial infarction

RESUMEN Introducción: La medida terapéutica más importante en pacientes con infarto agudo de miocardio con supradesnivel del segmento ST es la reperfusión del territorio isquémico; la fibrinólisis es la estrategia primaria en muchos hospitales. El diagnóstico temprano de aquellos pacientes con riesgo de fallo de trombólisis es vital. Objetivo: Identificar los factores pronósticos de fallo de trombólisis en pacientes con diagnóstico de infarto agudo de miocardio con supradesnivel del segmento ST. Métodos: Estudio descriptivo y prospectivo que incluyó a pacientes atendidos en la Emergencia del Hospital Clínico-Quirúrgico «Joaquín Albarrán¼, con diagnóstico de la enfermedad antes mencionada, y tratados con estreptoquinasa recombinante, entre noviembre de 2018 hasta mayo de 2020. Fueron incluidos 66 pacientes en la investigación. Las variables analizadas fueron: Edad, sexo, hipertensión arterial, diabetes mellitus, tiempo entre inicio de síntomas y comienzo de fibrinólisis, localización del infarto, duración del complejo QRS, duración y profundidad de onda. Resultados: Hubo fallo de trombólisis en 27 pacientes (40,9 %). Las variables: Tiempo de realización de trombólisis, duración y profundidad de la onda Q, así como la duración del QRS mostraron valores con diferencias significativas entre ambos grupos (p<0,05). El análisis multivariado confirmó la duración y profundidad de la onda Q como factores independientes, predictores de fallo de trombólisis: (OR= 14,50; IC 95 % 1,58-132,33); (OR: 1,69; IC 95 % 1,27-2,26), respectivamente. Conclusiones: El análisis de la profundidad y duración de la onda Q en el electrocardiograma inicial de los pacientes estudiados, permite predecir a una subpoblación de pacientes con riesgo de fallo de trombólisis.

ABSTRACT Introduction: the most important therapeutic measure in patients with ST-segment elevation acute myocardial infarction is reperfusion of the ischemic territory; fibrinolysis is the primary strategy in many hospitals. Early diagnosis of those patients with risk of failed thrombolysis is vital. Objective: to identify prognostic factors of thrombolytic failure in patients diagnosed with ST- segment elevation acute myocardial infarction. Methods: a descriptive and prospective study including patients treated in the Emergency department at "Joaquín Albarrán" Clinical and Surgical Hospital, who were diagnosed with the previously mentioned disease and treated with recombinant streptokinase, between November 2018 and May 2020. A number of 66 patients were included in the investigation. Age, gender, arterial hypertension, diabetes mellitus, time between onset of symptoms and onset of fibrinolysis, location of the infarction, QRS complex duration, duration and depth of the wave were the analyzed variables. Results: thrombolysis failed in 27 patients (40.9%). Time of performing thrombolysis, duration and depth of the Q wave, as well as the QRS duration showed values with significant differences between both groups (p<0.05). The multivariate analysis confirmed the duration and depth of the Q wave as independent factors, predictors of thrombolysis failure: (OR= 14.50; 95% CI 1.58-132.33); (OR: 1.69; 95% CI 1.27-2.26), respectively. Conclusions: the analysis of the depth and duration of the Q wave in the initial electrocardiogram of the studied patients allows us to predict a subpopulation of patients with risk of failed thrombolysis.

Efficacy of video-assisted thoracoscopic surgery versus intrapleural streptokinase for treatment of parapneumonic empyema with multiloculation and septation.

Introduction: Effective treatment of parapneumonic empyema with multiloculation and septation has been a challenge for clinicians for many years. Aim: This study compared the clinical outcomes of video-assisted thoracoscopic surgery (VATS) and intrapleural streptokinase in patients with stage II empyema. Material and methods: This is a retrospective study of 46 patients with parapneumonic empyema with multiloculation and septation in the pleural cavity treated with VATS or streptokinase in Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran, between January 2018 and January 2021. The main outcome measures of this study were hospital stay, febrile period, days with drainage, and treatment failure. Results: A total of 46 patients were included in this study. Of these, 28 were treated with VATS deloculation, and 18 were treated with streptokinase. The average hospital stay was 2.8 ±1.7 days for the VATS group and 7.5 ±3.5 days for the streptokinase group (p < 0.001). The average days with fever were 1.9 ±0.7 days for the VATS group and 3.0 ±1.64 days for the streptokinase group (p = 0.017). The average days with drainage were 3.0 ±1.6 days for the VATS group and 7.5 ±4.4 days for the streptokinase group (p < 0.001). The success rate was 92.9% for the VATS group and 66.7% for the streptokinase group, which was significantly higher in the VATS group compared to the streptokinase group (p = 0.042). No cases of perioperative mortality occurred. The frequency of adverse events did not differ between study groups (p > 0.05). Conclusions: Our results demonstrated that treatment of empyema with VATS is superior to streptokinase therapy.

Assessing the Efficacy and Outcomes Following Irrigation with Streptokinase Versus Hydrogen Peroxide in Necrotizing Pancreatitis: A Randomized Pilot Study.

BACKGROUND: Percutaneous catheter drainage (PCD's) are prone to blockage because of necrosum. To improve the efficacy of PCD, necrolytic agents have been used. The present study compared the use of Streptokinase with H2O2 in saline irrigation. MATERIALS AND METHODS: This is a single-center randomized pilot study (from July 2018 to Dec 2019). Patients with infected pancreatic necrosis not showing response to PCD and saline irrigation were included in the study. Patients received either Streptokinase (Streptokinase group 50,000 IU in 100 ml normal saline) or 3% H2O2 (3% H2O2 in 100 ml normal saline in 1:10 dilution). Primary endpoints were the need for surgery and mortality while secondary endpoints were hospital stay and complications attributable to necrolytic agents. RESULTS: There were 30 patients in the study, 15 in each arm. Organ failure was seen in 23 (76.6%), single organ failure was present in 11 (47%), and multi-organ failure in 12 (53%). Bleeding complications (20% in H2O2 vs 6.6% in Streptokinase), need for surgery (73% in H2O2 vs 33.3% in Streptokinase) and mortality (60% in H2O2 vs 33% in Streptokinase) were higher in H2O2 group but the difference was not significant statistically. Post-irrigation hospital stay was lesser in the Streptokinase group compared to H2O2 group but the difference did not reach statistical significance (14.1 ± 7.7 vs 19.2 ± 11.7, p = 0.09) CONCLUSIONS: Streptokinase irrigation led to a trend for reduced need for necrosectomy and mortality. H2O2 group had more bleeding complications. Post-irrigation hospital stay was lesser in Streptokinase group.

Clinical outcomes of patients with mitral prosthetic valve obstructive thrombosis treated with streptokinase or tenecteplase.

Agent of choice for thrombolytic therapy (TT) in prosthetic valve thrombosis (PVT) is unknown. 84 mitral obstructive-PVT episodes treated with TT (43: Tenecteplase; 41: Streptokinase) were included in this prospective study. The incidence of primary end-point (CCS: complete clinical success, defined as complete or partial hemodynamic success with no complications or surgery) was 84.5% with recurrent PVT as a sole predictor. Bleeding and embolic manifestations were noted in 8.3% and 4.7% of episodes respectively. Tenecteplase use was associated with lower complication rate and a mitral EOA of <0.74 cm2 at presentation predicts the need for extended thrombolysis (accuracy, 78.6%).

Insuficiencia renal aguda transitoria después de trombólisis coronaria con estreptoquinasa / Transient acute renal failure after coronary thrombolysis with streptokinase

Introducción: En la actualidad existen más de 150 medicamentos relacionados con la aparición de rabdomiólisis e insuficiencia renal aguda transitoria. La estreptoquinasa puede ser uno de ellos. Objetivo: Presentar un caso en el cual la administración de trombólisis con estreptoquinasa pudiera estar relacionado con una insuficiencia renal aguda transitoria. Caso clínico: Paciente de 38 años, con antecedentes de salud anterior y creatinina de 81 mg/L días antes del ingreso, sufrió infarto miocárdico agudo y después de la trombólisis con estreptoquinasa presentó dolores musculares intensos, náuseas, vómitos y lumbalgia intensa. La creatinina ascendió progresivamente; tuvo oligoanuria progresiva que evolucionó hasta las dos semanas y luego se recuperó. A los 21 días, la creatinina estaba en 116 mg/L. En la coronariografía, las coronarias son normales. Comentarios: Las causas de insuficiencia renal aguda transitoria pudieran ser, rabdomiólisis asociada con alteraciones del metabolismo del ATP y trastornos inmunológicos provocados por la administración de estreptoquinasa. La coronariografía resultó normal(AU)

Introduction: There are currently more than 150 medications related to the appearance of rhabdomyolysis and transient acute renal failure. Streptokinase can be one of them. Objective: Presenting a case the administration of streptokinase as a possible cause of acute, transient renal failure. Case report: A 38-year-old patient with a previous health history and 81 mg creatinine per liter days before admission, suffers acute myocardial infarction and after streptokinase thrombolysis he suffers severe muscle pain, nausea, vomiting, severe low back pain, creatinine ascends progressively and progressive oligoanuria that evolves until two weeks when it begins to return. At 21 days with 116 mg creatinine per liter, coronary angiography was performed with normal coronaries. Comments: The causes of transient acute renal failure may be rhabdomyolysis associated with abnormalities of the metabolism of ATP and immune disorders, caused by the administration of streptokinase. His coronary angiography was completely normal(AU)

Administración intrapleural de estreptoquinasa recombinante en tres niños graves con derrame pleural paraneumónico complicado / Intrapleural administration of recombinant streptokinase in three seriously ill children with complicated parapneumonic pleural effusion

Introducción: El derrame pleural paraneumónico es la enfermedad pleural más frecuente de la infancia, el 40-60 por ciento de los casos se presenta como complicación de neumonía adquirida en la comunidad. Ante la aparición de líquido pleural viscoso, con fibrina o tabiques, la fibrinólisis intrapleural aporta beneficios en la resolución de esta grave afección. Objetivo: Describir la evolución clínica e imagenológica de tres niños graves con derrame pleural paraneumónico complicado complejo y empiema. Presentación de casos: Pacientes ingresados en la Unidad de Terapia Intensiva del Hospital Pediátrico Provincial "Dr. Eduardo Agramonte Piña" con el diagnóstico de neumonía adquirida en la comunidad complicada con derrame pleural paraneumónico complicado complejo, tratados con estreptoquinasa recombinante por vía intrapleural; la primera paciente presentó crecimiento de Pseudomona en el cultivo de líquido pleural, patógeno no habitual en las infecciones respiratorias agudas procedentes de la comunidad. El segundo caso, se recibió complicada con shock séptico y el tercer paciente con ecografía torácica que mostró derrame pleural multitabicado, con grandes bolsones y gruesos tabiques. Los tres casos evolucionaron satisfactoriamente, sin necesidad de tratamiento quirúrgico, ni aparición de reacciones adversas atribuibles al fibrinolítico. Conclusiones: La administración intrapleural de la estreptoquinasa recombinante en niños graves con derrame pleural paraneumónico complicado complejo y empiema, resulta un método eficaz y seguro en la evacuación del foco séptico pleural, lo que favorece el control de la infección, sin aparición de complicaciones. Los casos presentados tuvieron evolución satisfactoria y en ninguno se produjo evento adverso relacionado con la administración de la estreptoquinasa recombinante intrapleural(AU)

Introduction: Parapneumonic pleural effusion is the most common pleural disease in childhood; 40-60 percent of cases occur as a complication of community-acquired pneumonia. Given the onset of viscous pleural fluid, with fibrin or septums, intra-pleural fibrinolysis provides benefits to solve this serious condition. Objective: Describe the clinical and imaging evolution of three seriously ill children with complex complicated parapneumonic pleural effusion and empyema. Case presentation: Patients admitted to the Intensive Therapy Unit of "Dr. Eduardo Agramonte Piña" Provincial Pediatric Hospital with the diagnosis of pneumonia acquired in the community worsen with complex complicated parapneumonic pleural effusion, and treated in the intrapleural way with recombinant streptokinase. The first patient showed growth of Pseudomona in the culture of pleural fluid, a pathogen which is not common in acute respiratory infections from the community. The second case was complicated with septic shock; and the third patient had a chest ultrasound that showed multi-sited pleural effusion, with large bags and thick septums. All three cases evolved satisfactorily, without needing surgical treatment, or having adverse reactions attributable to fibrinolytic ones. Conclusions: Intrapleural administration of recombinant streptokinase in seriously ill children with complex complicated parapneumonic pleural effusion and empyema is an effective and safe method in the evacuation of pleural septic focus, which favors infection control, without complications. The cases presented had satisfactory evolution and none of them occurred adversely related to the administration of intrapleural recombinant streptokinase(AU)

Perfil clínico y angiográfico de las mujeres con infarto agudo al miocardio en un hospital nacional / Clinical and angiographic profile of women with acute myocardial infarction in a national hospital

Resumen Justificación: La cardiopatía isquémica es la principal causa de muerte de mujeres en Costa Rica, y su incidencia ha aumentado con los años. A pesar de esto, hay pocos estudios clínicos a este respecto en nuestro país. El objetivo del presente trabajo es presentar las principales características clínicas y angiográficas de un grupo de pacientes con infarto agudo del miocardio con la idea de establecer no solo sus particularidades sino permitir comparaciones con otras poblaciones. Métodos: Se trató de un estudio observacional, descriptivo y retrospectivo, de un periodo de cinco años, en el cual se incluyeron a las pacientes ingresadas con infarto del miocardio a la Unidad de Cuidados Intensivos. Se registraron datos demográficos, de evolución clínica, complicaciones, hallazgos angiográficos, tratamiento y desenlace. El análisis estadístico fue cuantitativo descriptivo, realizado con el programa informático SPSS v.21 (IBM Corp., EEUU) y éste consistió en cálculos de frecuencia, tendencia central, medidas de variabilidad de rango, percentiles, y chi-cuadrado. El protocolo de la investigación fue aprobado por el Comité Ético Científico del Hospital Rafael Ángel Calderón Guardia (DG-3380-2020). Resultados: De 190 pacientes se incluyeron un total de 54. La edad promedio fue de 60 años, con una mortalidad del 17,9%, la cual fue 5,4 % más alta que en los hombres. La mayor parte de las pacientes padecía de hipertensión arterial (74%), 24 (44,5%) eran taba- quistas y 23 (42,5%) tenían diabetes mellitus. Los síntomas más frecuentes fueron: dolor torácico, criodiaforesis y disnea. Se consideró que hubo dolor torácico atípico en 8 casos (15%). A 48 pacientes se le llevó a angioplastia coronaria y solo 35% la recibieron en tiempo oportuno. A 17 pacientes se les aplicó trombólisis farmacológica y solo en 3 pacientes fue exitosa. La arteria coronaria derecha y la arteria descendente anterior fueron los vasos responsables en la mayoría de los casos (19 casos (39,5%) cada uno de ellas.) Conclusión: Esta población tuvo síntomas isquémicos claros, con enfermedad coronaria severa y una mortalidad mayor que los hombres. En general la terapia farmacológica, así como la mecánica se aplicaron en forma tardía.

Abstrac Justification: The ischemic heart disease is the main cause of death of women in Costa Rica, and its incidence has increased with the years. In spite of this, there are few clinical studies in this respect in our country. The aim of this paper is to present the main clinical and angiographic characteristics of a group of patients with acute myocardial infarction in order to establish not only their particularities but also to allow comparisons with other populations. Methods: An observational, descriptive and retrospective study was carried out over a period of five years, in which patients admitted with myocardial infarction to the Intensive Care Unit were included. Demographic data, clinical evolution, complications, angiographic findings, treatment, and outcome were recorded. Statistical analysis was quantitative and descriptive, performed with SPSS v.21 software (IBM Corp., USA) and consisted of calculations of frequency, central tendency, measures of variability, percentiles, and chi-square. The Ethical Committee of the Hospital Rafael Angel Calderon Guardia approved the research protocol (DG-3380-2020). Results: A total of 54 out of 190 patients were included. The average age was 60 years, with a mortality rate of 17.9%, which was 5.4% higher than in men. Most of the patients suffered from arterial hypertension (74%), 24 (44.5%) were smokers and 23 (42.5%) had diabetes mellitus. The most frequent symptoms were chest pain, cryodiaphoresis and dyspnea. It was considered that there was atypical chest pain in 8 cases (15%). Forty-eight patients were taken for coronary angioplasty and only 35% received it in time. Pharmacological thrombolysis was applied to 17 patients, and it was successful in only 3 patients. The right coronary artery and the anterior descending artery were the vessels responsible in most cases (19 cases (39.5%) each). Conclusión: This population had clear ischemic symptoms, with severe coronary disease and higher mortality than men. In general, pharmacological as well as mechanical therapy was applied late.

Comparison of QT dispersion in patients with ST elevation acute myocardial infarction (STEMI) before and after treatment by streptokinase versus primary percutaneous coronary intervention (PCI).

BACKGROUND: QT dispersion (QTD) represents inhomogeneous ventricular repolarization such that an increased QTD may predispose the heart to malignant ventricular arrhythmias (VAs). This study was conducted to compare QTD in patients with ST-elevation myocardial infarction (STEMI) before and after treatment by streptokinase (SK) versus primary percutaneous coronary intervention (PCI). METHODS: The present case-control study was conducted on 185 STEMI patients who received SK (115 cases) or underwent primary PCI (70 cases). QTD and QT corrected dispersion before and 24 h after treatment. Likewise, they were also found to correct fatal arrhythmias (VT and VF) during the first 24 h after admission, and ejection fraction (EF) 24 h after treatment was evaluated. RESULTS: QTD decreased in the primary PCI group, though no significant difference was seen between the two studied groups (P > 0.05). A significant increase was detected in the EF mean values for the primary PCI-treated patients (P = 0.022). Moreover, there was a significant reduction in QTD of patients with fatal arrhythmias in the primary PCI group (P = 0.022). CONCLUSION: An overall QTD reduction in the primary PCI group and a significant decrease in QTD of patients with fatal arrhythmias in the primary PCI group show that this treatment strategy is more efficient than thrombolytic therapy. As an important indicator of proper myocardial function, EF can independently predict improved myocardial function in the primary PCI group.

Eficacia y seguridad de la estreptoquinasa recombinante en niños con derrame pleural paraneumónico / Effectiveness and security of recombinant streptokinase in children with parapneumonic pleural efussion

Introducción: El derrame pleural paraneumónico como complicación de neumonías adquiridas en la comunidad en la población pediátrica constituye un problema de salud mundial y en Cuba. El empleo de fibrinolíticos intrapleurales es una acertada opción terapéutica. Objetivo: Evaluar la eficacia y seguridad de la utilización de la estreptoquinasa recombinante en el tratamiento del derrame pleural paraneumónico complicado complejo en niños. Métodos: Ensayo clínico confirmatorio fase III, monocentro, abierto, aleatorizado y controlado (RPCEC00000292), realizado entre septiembre 2018 - octubre 2019. Se incluyeron niños (1 - 18 años de edad), que cumplieron los criterios de selección, incluida la voluntariedad. Todos recibieron el tratamiento convencional establecido y se distribuyeron en dos grupos: I-experimental (estreptoquinasa recombinante, dosis diaria intrapleural de 200 000 UI, 3-5 días); II-control (terapia convencional). Las variables principales fueron: necesidad de cirugía y la estadía hospitalaria. Se evaluaron también los eventos adversos. Resultados: Se evaluaron 55 niños con la enfermedad referida, de ellos, 34 (61,8 por ciento) se incluyeron en el estudio. Ningún paciente del grupo experimental requirió cirugía, a diferencia del grupo control que lo requirió en 25 por ciento. Se redujo significativamente la estadía hospitalaria en el grupo que recibió estreptoquinasa recombinante. No se presentaron eventos adversos graves atribuibles al tratamiento experimental. Conclusiones: La estreptoquinasa recombinante administrada en el derrame pleural paraneumónico complicado complejo resultó un método eficaz y seguro para la evacuación del foco séptico, con un impacto positivo expresado en la reducción de complicaciones, la necesidad de tratamiento quirúrgico y la estadía hospitalaria, sin la ocurrencia de eventos adversos relacionados con su uso(AU)

in the community by the pediatric population represents a health problem in the world and in Cuba. The use of intrapleural fibrinolytics is a good therapeutic option. Objective: To evaluate the effectiveness and security of the use of recombinant streptokinase in the treatment of complex parapneumonic pleural efussion in children. Methods: Phase III confirmatory clinical trial, monocentric, open, randomized and controlled (RPCEC00000292) - named as DENIS study- carried out from September 2018 to October, 2019. There were included children (from 1 to 18 years old) that met the selection criteria including voluntariness. All of them received the established conventional treatment and were distributed in two groups: I- experimental (recombinant streptokinase, intrapleural daily dose of 200 000 UI, 3 - 5 days); II- control (conventional therapy). The main variables were need of surgery and hospital stay. There were also assessed the adverse events. Results: 55 children with the above mentioned disease were assessed; 34 of them (61.8 percent) were included in the study. Any of the patients of the experimental group required surgery, opposite to the control group that required it in a 25 percent. The hospital stay was significantly reduced in the group that had treatment with recombinant streptokinase. There were not any severe adverse events related to the experimental treatment. Conclusions: When recombinant streptokinase was administered in the complex parapneumonic pleural efussion resulted in an efficient and safe method for the elimination of the septic focus, with a positive impact expressed in the reduction of complications, the need of surgical treatment and the hospital stay without presenting related adverse events while using it(AU)

Re-establishing indwelling pleural catheter patency with alteplase after failure of streptokinase.

Indwelling pleural catheter (IPC) has revolutionized the management of malignant pleural effusion (MPE). IPC is relatively safe, although complications can occur. We report a 53-year-old woman with stage IVA lung adenocarcinoma and recurrent MPE. Two months post insertion, the IPC was blocked with residual effusion and presence of new loculations. Attempts to restore patency with six doses of intrapleural (IP) streptokinase failed. She was referred to our centre for further management. We used a single dose of 2.5 mg IP alteplase which was successful in establishing patency of the IPC and draining the effusion. This case highlights the safety and efficacy of IP alteplase via IPC following a failed instillation of streptokinase.

Short-Term Clinical Follow-Up After Thrombolytic Therapy in Patients With Prosthetic Valve Thrombosis: A Single-Center Experience.

BACKGROUND: Thrombolytic therapy has evolved as an alternative to surgery for prosthetic valve thrombosis (PVT). Therefore, this retrospective, single-center study aimed to evaluate the clinical profile of PVT and the role of thrombolytic therapy in patients with PVT. METHODS: Data from a total of 16 consecutive patients with PVT enrolled between January 2017 and January 2018 at a tertiary care center in India were retrospectively evaluated. PVT was diagnosed based on clinical presentation, transthoracic echocardiography, and fluoroscopy. All patients received 0.25 MU intravenous (IV) bolus streptokinase over 30 min, followed by a 0.1 MU/h IV infusion for a maximum of 72 h. Transthoracic echocardiography and fluoroscopy were repeated after completion of thrombolysis session. The clinical endpoints were death and hemodynamic success within 24 h of thrombolytic therapy or during the hospital stay, and major complications, including stroke or major bleeding (intracranial bleed or bleeding requiring transfusion or surgical treatment) during the hospital stay and within 3 months of thrombolytic therapy. RESULTS: The median age of the patients was 40 ± 11.60 years and about 62.5% (n = 10) were females. The median time between the valve placement and presentation for PVT was 3 years (range: 1 - 4 years). The peak gradient across the thrombotic mitral and aortic valve was 43.79 ± 18.47 and 93.5 ± 33.11 mmHg, respectively. At 3 days post-thrombolysis, peak gradient across both mitral valve (15.91 ± 7.56; mean gradient: 8.45 ± 4.01) and aortic valve (23.50 ± 6.45; mean gradient: 13.60 ± 3.83) decreased significantly (P ≤ 0.05). The thrombolytic therapy was successful in 13 (81.25%) patients. While, two (12.50%) patients died, none developed stroke or myocardial infarction during the study period. CONCLUSIONS: The present study with short-term follow-up demonstrated the acceptable clinical efficacy of thrombolytic therapy. However, larger trials with a greater number of patients and longer follow-up are warranted to establish the safety and effectiveness of thrombolytic therapy in patients with PVT.

[Comparative efficacy of various thrombolytic agents in treatment of pulmonary embolism]. / Sravnitel'naia éffektivnost' razlichnykh tromboliticheskikh preparatov v lechenii tromboémbolii legochnoi arterii.

The authors carried out a retrospective analysis of clinical efficacy of streptokinase and alteplase (actilyse®) in patients presenting with high- and intermediate-to-high risk pulmonary artery thromboembolism (PATE) who were discharged from hospital after appropriate treatment performed. Of the total number of the treated patients, we formed 2 groups comprising 20 patients each, receiving alteplase (group 1) and streptokinase (group 2). The patients were comparable by the main clinical characteristics, predisposing factors, severity of pulmonary artery thromboembolism (PATE) and duration of treatment. Efficacy of thrombolytic therapy assessed clinically and instrumentally did not differ. However, by the stratified risk and frequency of PATE relapses, the condition of patients receiving alteplase turned out to be more severe. Based on the obtained results, a conclusion was made that actilyse is a drug of choice for treatment of patients with PATE.

Structural Biology and Protein Engineering of Thrombolytics.

Myocardial infarction and ischemic stroke are the most frequent causes of death or disability worldwide. Due to their ability to dissolve blood clots, the thrombolytics are frequently used for their treatment. Improving the effectiveness of thrombolytics for clinical uses is of great interest. The knowledge of the multiple roles of the endogenous thrombolytics and the fibrinolytic system grows continuously. The effects of thrombolytics on the alteration of the nervous system and the regulation of the cell migration offer promising novel uses for treating neurodegenerative disorders or targeting cancer metastasis. However, secondary activities of thrombolytics may lead to life-threatening side-effects such as intracranial bleeding and neurotoxicity. Here we provide a structural biology perspective on various thrombolytic enzymes and their key properties: (i) effectiveness of clot lysis, (ii) affinity and specificity towards fibrin, (iii) biological half-life, (iv) mechanisms of activation/inhibition, and (v) risks of side effects. This information needs to be carefully considered while establishing protein engineering strategies aiming at the development of novel thrombolytics. Current trends and perspectives are discussed, including the screening for novel enzymes and small molecules, the enhancement of fibrin specificity by protein engineering, the suppression of interactions with native receptors, liposomal encapsulation and targeted release, the application of adjuvants, and the development of improved production systems.

Evaluation of Activity Kinetic Parameters of SK319cys, As a New Cysteine Variant of Streptokinase: A Comparative Study.

BACKGROUND: Despite the extensive use of streptokinase in thrombolytic therapy, its administration may have some shortcomings like allergic reactions and relatively low half life. Specific PEGylation on cysteine at desired sites of streptokinase may alleviate these deficiencies and improve the quality of treatment. OBJECTIVE: This study was carried out to create a new cystein variant of streptokinase and compare its activity with formerly mutated SK263cys, SK45cys and intact streptokinase (Ski) to introduce superior candidates for specific PEGylation. METHOD: In silico study was carried out to select appropriate amino acid for cysteine substitution and accordingly mutagenesis was carried out by SOEing PCR. The mutated gene was cloned in E. coli, expressed, and purified by affinity chromatography. Activity of the purified proteins was assayed and kinetic parameters of enzymatic reaction were analyzed. RESULTS: According to in silico data, Arginine319 was selected for substitution with cysteine. SK319cys was achieved with 98% purity after cloning, expression and purification. It was shown that the enzymatic efficiency of SK319Cys and SK263cys was increased 18 and 21%, respectively, when compared to SKi (79.4 and 81.3 vs. 67.1µM-1min-1), while SK45cys showed 7% activity decrease (62.47µM-1min-1) compared to SKi. According to time-based activity assay, SK319Cys and SK263cys exhibited higher activity at lower substrate concentrations (100 and 200 µM), but at higher concentrations of substrate (400 and 800 µM), the proteins showed a very close trend of activity. CONCLUSION: SK319cys, as the new cysteine variant of streptokinase, together with SK263cys and SK45cys can be considered as appropriate molecules for specific PEGylation.

Enhanced Production Of Streptokinase By Chemical Mutagenesis Of Streptococcus agalactiae EBL-20

Abstract Streptokinase (SK) is an enzyme that is used for the treatment of cardiovascular diseases. The current study focused on the enhanced production of SK by inducing mutation in Streptococcus agalactiae EBL-20 and optimization of medium components and culture conditions for the maximum growth of mutant derived strain. S. agalactiae EBL-32 was selected as a potent mutant after exposure of S. agalactiae EBL-20 to EMS for 180 minutes. SK activity obtained from mutant derived strain was found to be 1.6 fold higher as compared to the activity achieved by wild strain. Nutritional requirements of the mutated strain were optimized by single factor analysis method suggesting glucose as the optimum carbon source; yeast extract and peptone as a suitable nitrogen sources and corn steep liquor (CSL) as an appropriate substrate for the maximum SK production. The culture conditions determined by response surface methodology (RSM) suggested that a temperature value of 37.5⁰C and pH 7 of the fermentation medium with 2.50 mL inoculum size for 36 hours of incubation was optimum for maximum yield of SK. Hence the optimization studies resulted into 1.92 fold increase in the yield of SK suggesting the new isolate suitable for commercial scale production of SK.

Uso de estreptoquinasa recombinante intrapleural en una mujer embarazada con empiema pleural / Use of intrapleural recombinant streptokinase in a pregnant woman with pleural empyema

RESUMEN Fundamento: la neumonía complica el 0,78-2,7 por 1 000 embarazos al estar en riesgo la madre y el feto. El empiema como complicación de una neumonía en una paciente embarazada agrega un alto índice de morbimortalidad para la madre y el feto si no se actúa de forma rápida. Objetivo: describir el caso de una mujer de 33 semanas de embarazo, la cual desarrolló un empiema pleural producto de una complicación de una neumonía adquirida en la comunidad tratada con fibrinólisis intrapleural. Caso clínico: paciente gestada de 33 semanas, asmática ingresada en el servicio de terapia intensiva del Hospital Universitario Manuel Ascunce Domenech con el diagnóstico de neumonía grave adquirida en la comunidad complicada con derrame paraneumónico el cual evolucionó hacia el empiema. El mismo fue tratado con tubo de toracostomía y terapia fibrinolítica, con buena evolución clínica y radiológica. Conclusiones: la estreptoquinasa recombinante se puede utilizar de manera segura y efectiva para el manejo del empiema pleural, como agente fibrinolítico intrapleural, durante el embarazo.

ABSTRACT Background: pneumonia complicates 0,78-2,7 per 1 000 pregnancies placing the mother and the fetus at risk. Empyema as a complication of pneumonia in a pregnant patient adds a high rate of morbidity and mortality to the mother and the fetus if one does not act quickly. Objective: to present the case of a pregnant woman of 33 weeks who developed a pleural empyema resulting from acquired pneumonia. Clinical case: 33-week gestated patient, asthmatic admitted to the intensive care unit of the University Hospital Manuel Ascunce Domenech with the diagnosis of severe pneumonia acquired in the community complicated with para-pneumonic effusion, which evolved into empyema. It was treated with a thoracotomy tube and fibrinolytic therapy, with good clinical and radiological evolution. Conclusions: Recombinant streptokinase can be used safely and effectively for the management of PE, as an intrapleural fibrinolytic agent, during pregnancy.

Tenecteplase versus streptokinase thrombolytic therapy in patients with mitral prosthetic valve thrombosis.

OBJECTIVE: Prosthetic valve thrombosis (PVT) is a dreadful complication of mechanical prosthetic valves. Thrombolytic therapy (TT) for PVT is an alternative to surgery and currently making a leading role. This study compares TT with tenecteplase (TNK) and streptokinase (SK) head to head in patients with mitral PVT. METHODS: In this single center, observational study, patients with mitral PVT diagnosed by clinical data, transthoracic echocardiography, transesophageal echocardiography, and fluoroscopy were included. After excluding patients with contraindications for thrombolysis, they were randomly assigned to receive either SK or TNK regimen. Patients were monitored for success or failure of TT and for any complications. RESULTS: Among 52 episodes (47 patients with 5 recurrences) of mechanical mitral PVT, 40 patients were thrombolyzed with SK and 12 patients were thrombolyzed with TNK. Baseline characteristics including demographic profile, clinical and echocardiographic features, and valve types were not statistically significant between the groups. Complete success rate was 77.5% in SK group and 75% in TNK group (p=0.88). Partial success rate, failure rate, and major complications were not statistically significant between the two groups. Within 12h of therapy, TNK showed complete success in 33.3% of patients compared to 15% in SK group (p-value <0.02). Minor bleeding was more common in TNK group. CONCLUSION: Slow infusion of TNK is equally efficacious but more effective than SK in the management of mitral mechanical PVT. 75% to 77.5% of PVT patients completely recovered from TT and it should be the first line therapy where the immediate surgical options were remote.