ADAMTS13 recovery in acute thrombotic thrombocytopenic purpura after caplacizumab therapy.

ABSTRACT: Caplacizumab prevents the interaction between von Willebrand factor and platelets and is used to treat immune thrombotic thrombocytopenic purpura (iTTP). Its administration has been associated with a delay in ADAMTS13 activity restoration after plasma exchange (PEX) suspension. We analyzed the outcomes of 113 iTTP episodes, 75 of which were treated with caplacizumab, in 108 patients from the Spanish Registry of Thrombotic Thrombocytopenic Purpura. Caplacizumab shortened the time to platelet count normalization and reduced PEX requirement, exacerbations, and relapses. There was no difference in the time to achieve ADAMTS13 activity ≥20% after PEX end between caplacizumab-treated and nontreated episodes (median [interquartile range], 14.5 [7.7-27.2] vs 13.0 [8.0-29.0] days, P = .653). However, considering the 36 episodes in which caplacizumab was started ≤3 days after iTTP diagnosis, the time for ADAMTS13 restoration from PEX end was higher than in those episodes in which caplacizumab was started >3 days after iTTP diagnosis (20.0 [12.0-43.0] vs 11.0 [3.5-20.0] days, P = .003) or than in non-caplacizumab-treated episodes (P = .033). This finding could be related to a significantly shorter duration of PEX in early caplacizumab-treated episodes than in late caplacizumab-treated episodes (5.5 [4.0-9.0] vs 15.0 [11.0-21.5] days, P < .001) or non-caplacizumab-treated episodes (11.0 [6.0-26.0] days, P < .001). There were no differences in time to ADAMTS-13 restoration from PEX start (28.0 [17.2-47.5], 27.0 [19.0-37.5] and 29.5 [15.2-45.0] days in early caplacizumab-treated, late caplacizumab-treated and non-caplacizumab-treated episodes). Early administered caplacizumab does not prevent the requirement for immunosuppression but has beneficial effects by shortening PEX requirement without major safety concerns.

[Clinical practice guideline for Diagnosis and management of cholelithiasis, cholecystitis and choledocholithiasis for the Peruvian Social Security (EsSalud)]. / Guía de práctica clínica para el diagnóstico y manejo de la colelitiasis, colecistitis aguda y coledocolitiasis en el Seguro Social del Perú (EsSalud).

INTRODUCTION: This article summarizes the clinical practice guide (CPG) for the diagnosis and management of cholelithiasis, acute cholecystitis and choledocholithiasis in the Peruvian Social Security (EsSalud). OBJECTIVE: To provide clinical recommendations based on evidence for the management of patients with cholelithiasis, acute cholecystitis and choledocholithiasis in EsSalud. METHODS: a guideline task force (GTF) was formed with internists, general surgeons, gastroenterologists, and methodologists. The group proposed 10 clinical questions to be answered in this Clinical practice guideline (CPG). Systematic searches of preview reviews were performed and when it was necessary, primary studies from PubMed and CENTRAL during 2017 were reviewed. The evidence was selected aiming to answer each proposed question. Certainty of evidence was evaluated using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodical work sessions, the group used GRADE methodology for reviewing the evidence and formulating recommendations, good clinical practice items and three flowcharts for diagnosis and treatment. Finally, the CPG was approved by Resolution Nº 046-IETSI-ESSALUD-2017. RESULTS: This CPG approached 10 clinical questions divided into two topics: diagnosis and management. Based on these questions; one strong recommendation, five weak recommendations, and 17 good clinical practice items and three flowcharts were formulated. CONCLUSION: This paper abstracts the methodology and evidence-based conclusions of the CPG for diagnosis and management of cholelithiasis, acute cholecystitis and choledocholithiasis in EsSalud.

Design and Synthesis of Water-Soluble and Potent MMP-13 Inhibitors with Activity in Human Osteosarcoma Cells.

Osteoarthritis is a degenerative disease, often resulting in chronic joint pain and commonly affecting elderly people. Current treatments with anti-inflammatory drugs are palliative, making the discovery of new treatments necessary. The inhibition of matrix metalloproteinase MMP-13 is a validated strategy to prevent the progression of this common joint disorder. We recently described polybrominated benzotriazole derivatives with nanomolar inhibitory activity and a promising selectivity profile against this collagenase. In this work, we have extended the study in order to explore the influence of bromine atoms and the nature of the S1' heterocyclic interacting moiety on the solubility/selectivity balance of this type of compound. Drug target interactions have been assessed through a combination of molecular modeling studies and NMR experiments. Compound 9a has been identified as a water-soluble and highly potent inhibitor with activity in MG-63 human osteosarcoma cells.

[Clinical practice guidelines for the diagnosis and management chronic infection of hepatitis viral C of the Peruvian Health Social Security (EsSalud)]. / Guía de práctica clínica para el diagnóstico y tratamiento de la infección crónica por el virus de hepatitis C en el Seguro Social de Salud del Perú (EsSalud).

INTRODUCTION: This article summarizes the clinical practice guidelines (CPG) for the diagnosis and treatment of chronic infection of hepatitis viral C of the Peruvian Health Social Security (EsSalud). OBJECTIVE: To provide clinical recommendations based on evidence for the diagnosis and treatment of chronic infection of hepatitis viral C in EsSalud. METHODS: A guideline development group (GDG) was established, including medical specialists and methodologists. The GDG formulated 4 clinical questions to be answered in this CPG. Systematic searches of systematic reviews and primary studies (when pertinent) were conducted in PubMed, and Central (Cochrane) during 2019. The evidence was selected to answer each of the clinical questions. The accuracy of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic work meetings, the GEG used the GRADE methodology to review the evidence and formulate the recommendations, the points of good clinical practice and the treatment flowchart. Finally, the CPG was approved with Resolution No. 151-IETSIESSALUD-2019. RESULTS: The present CPG addressed 4 clinical questions of four topics: screening, diagnosis, staging and treatment. Based on these questions, 13 recommendations (8 strong recommendations and 5 weak recommendations), 27 points of good clinical practice, and 1 flowchart were formulated. CONCLUSION: This paper summarizes the methodology and evidencebased conclusions from the CPG for for the diagnosis and treatment of chronic infection of hepatitis viral C of the EsSalud.

Probable Syphilitic Aortitis Documented by Positron Emission Tomography.

Positron emission tomography (PET) has been used to aid in diagnosis of inflammatory and infectious disease. We describe the case of a patient with early latent syphilis with increased metabolic activity along the aorta detected via PET, suggesting probable aortitis. Three months after treatment, the PET showed apparent resolution of the aortitis.

Clinical practice guideline for the prevention and management of hypertensive disorders of pregnancy / Guía de práctica clínica para la prevención y el manejo de la enfermedad hipertensiva del embarazo

Objectives: To provide clinical recommendations based on evidence for the the prevention and management of HDP in EsSalud. Methods: A CPG for the the prevention and management of HDP in EsSalud was developed. To this end, a guideline development group (local GDG) was established, including medical specialists and methodologists. The local GDG formulated 8 clinical questions to be answered by this CPG. Systematic searches of systematic reviews and­when it was considered pertinent­primary studies were searched in PubMed y Central during 2021. The evidence to answer each of the posed clinical questions was selected. The quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic work meetings, the local GDG used the GRADE methodology to review the evidence and formulate the recommendations, the points of good clinical practice and flowcharts for the prevention, management and follow-up. Finally, the CPG was approved with Resolution 112-IETSI-ESSALUD-2021. Results: This CPG addressed 8 clinical questions, divided into three topics: prevention, management and follow-up of the HDP. Based on these questions, 11 recommendations (6 strong recommendations and 5 weak recommendations), 32 points of good clinical practice, and 3 flowcharts were formulated. Conclusions: The main recommendations in the guideline are the use of magnesium sulfate for the treatment of severe pre-eclampsia and eclampsia. The guideline must be updated in three years' time.

Objetivos: proveer recomendaciones clínicas basadas en evidencia para la prevención y el manejo de la enfermedad hipertensiva del embarazo EHE en EsSalud. Materiales y métodos: se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos. El GEG formuló ocho preguntas clínicas para ser respondidas por la presente Guía de Práctica Clínica (GPC). Se realizaron búsquedas sistemáticas de revisiones sistemáticas y, cuando se consideró pertinente, estudios primarios en PubMed y Central durante 2021. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas. La certeza de la evidencia fue evaluada usando la metodología. En reuniones de trabajo periódicas, el GEG usó la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE) para calificar la evidencia y formular las recomendaciones. Además se resentan los puntos de buenas prácticas clínicas (BPC) y los flujogramas de prevención, manejo y seguimiento. Finalmente, la GPC fue aprobada por Resolución 112-IETSI-ESSALUD-2021. Resultados: en la presente GPC se formularon 11 recomendaciones (6 fuertes y 5 condicionales) que respondieron las preguntas clínicas definidas en el alcance de la GPC, acompañadas de 32 BPC y 3 flujogramas que abordan temas de prevención tratamiento y seguimiento de la EHE Conclusiones: como recomendaciones centrales de la guía se dan el uso de sulfato de magnesio para el tratamiento de la preeclampsia severa y la eclampsia. La guía deberá ser actualizada en tres años.

SARS-CoV-2 seroprevalence study in Lambayeque, Peru. June-July 2020.

BACKGROUND: Estimating the cumulative prevalence of SARS-COV-2 will help to understand the epidemic, contagion, and immunity to COVID-19 in vulnerable populations. The objective is to determine the extent of infection in the general population and the cumulative incidence by age group. METHODS: It was carried out with a longitudinal analytical study, in the population of the Lambayeque region, located in the north of Peru. The selection was carried out in multistages (districts, area, household, and finally choosing the interviewee within the house). Seroprevalence was estimated as a positive result of the rapid test whether it was positive IgM or positive IgG. An adjustment was made for the sampling weights used. RESULTS: The seroprevalence found in the region was 29.5%. Young people between 21 and 50 years old presented the highest seroprevalence frequencies. A total of 25.4% were asymptomatic. The most frequent complaint was dysgeusia and dysosmia (85.3% and 83.6%). Dysosmia (PR = 1.69), chest pain (PR = 1.49), back pain (PR = 1.45), cough (PR = 1.44), fever (PR = 1.41), general malaise (PR = 1.27) were associated factors with the higher the frequency of seropositivity for SARS-CoV-2. Reporting of complete isolation at home decreased the frequency of positivity (PR = 0.80), however, reporting having ARI contact (PR = 1.60), having contact with a confirmed case (PR = 1.51), and going to market (PR = 1.26) increased the frequency of positivity for SARS-CoV-2. CONCLUSION: These results suggest that Lambayeque is the region with the highest seroprevalence in the world, well above Spain, the United States and similar to a study in India.

Vascular Endothelial Growth Factor (VEGF) Prevents the Downregulation of the Cholinergic Phenotype in Axotomized Motoneurons of the Adult Rat.

Vascular endothelial growth factor (VEGF) was initially characterized by its activity on the vascular system. However, there is growing evidence indicating that VEGF also acts as a neuroprotective factor, and that its administration to neurons suffering from trauma or disease is able to rescue them from cell death. We questioned whether VEGF could also maintain damaged neurons in a neurotransmissive mode by evaluating the synthesis of their neurotransmitter, and whether its action would be direct or through its well-known angiogenic activity. Adult rat extraocular motoneurons were chosen as the experimental model. Lesion was performed by monocular enucleation and immediately a gelatine sponge soaked in VEGF was implanted intraorbitally. After 7 days, abducens, trochlear, and oculomotor nuclei were examined by immunohistochemistry against choline acetyltransferase (ChAT), the biosynthetic enzyme of the motoneuronal neurotransmitter acetylcholine. Lesioned motoneurons exhibited a noticeable ChAT downregulation which was prevented by VEGF administration. To explore whether this action was mediated via an increase in blood vessels or in their permeability, we performed immunohistochemistry against laminin, glucose transporter-1 and the plasmatic protein albumin. The quantification of the immunolabeling intensity against these three proteins showed no significant differences between VEGF-treated, axotomized and control animals. Therefore, the present data indicate that VEGF is able to sustain the cholinergic phenotype in damaged motoneurons, which is a first step for adequate neuromuscular neurotransmission, and that this action seems to be mediated directly on neurons since no sign of angiogenic activity was evident. These data reinforces the therapeutical potential of VEGF in motoneuronal diseases.

Guía de práctica clínica para el manejo de la Enfermedad Renal Crónica estadíos 3b, 4 y 5 en el Seguro Social de Salud del Perú (EsSalud)

Introducción: El presente artículo resume la guía de práctica clínica (GPC) para el manejo de la enfermedad renal crónica estadíos 3b, 4 y 5 en el Seguro Social del Perú (EsSalud). Objetivo: Proveer recomendaciones clínicas basadas en evidencia para el manejo de pacientes con enfermedad renal crónica estadíos 3b, 4 y 5 en EsSalud. Métodos: Se conformó un grupo elaborador de la guía (GEG) que incluyó especialistas y metodólogos. El GEG formuló 9 preguntas clínicas. Se realizó búsquedas sistemáticas de revisiones sistemáticas y estudios primarios en PubMed entre diciembre del 2020 y agosto del 2021. Se seleccionó la evidencia para responder a las preguntas clínicas planteadas. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). El GEG usó la metodología GRADE para revisar la evidencia y formular recomendaciones, los puntos de buena práctica clínica (BPC) y los flujogramas de manejo. Finalmente, la GPC fue aprobada con Resolución N° 88-IETSI-ESSALUD-2021. Resultados: La presente GPC abordó 9 preguntas clínicas. En base a dichas preguntas se formularon 17 recomendaciones (7 fuertes y 10 condicionales), 28 BPC, y 4 flujogramas de manejo. Conclusión: El presente artículo resume la metodología y las conclusiones basadas en evidencias de la GPC para el manejo de la Enfermedad Renal Crónica estadíos 3b, 4 y 5 en EsSalud.

Introduction: This article summarizes the clinical practice guideline (CPG) for the management of stage 3b, 4, and 5 chronic kidney disease (CKD) in the Social Security of Peru (EsSalud). Objective: To provide evidence-based clinical recommendations for the management of stage 3b, 4, and 5 CKD in EsSalud. Methods: A guideline development group (GDG) was formed, including specialists and methodologists. The GDG formulated 9 clinical questions. Systematic searches for systematic reviews and primary studies were conducted in PubMed from December 2020 to August 2021. Evidence was selected to answer the clinical questions posed. The certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The GDG used the GRADE methodology to review the evidence and formulate recommendations, points of good clinical practice (GPC), and management flowcharts. Finally, the CPG was approved with Resolution No. 88-IETSI-ESSALUD-2021. Results: This CPG addressed 9 clinical questions. Based on these questions, 17 recommendations (7 strong and 10 conditional), 28 GPC points, and 4 management flowcharts were formulated. Conclusion: This article summarizes the methodology and evidence-based conclusions of the CPG for the management of stage 3b, 4, and 5 CKD in EsSalud.

Guía de práctica clínica para el diagnóstico y manejo de la colelitiasis, colecistitis aguda y coledocolitiasis en el Seguro Social del Perú (EsSalud) / Clinical practice guideline for Diagnosis and management of cholelithiasis, cholecystitis and choledocholithiasis for the Peruvian Social Security (EsSalud)

RESUMEN Introducción: El presente artículo resume la guía de práctica clínica (GPC) para el diagnóstico y manejo de los pacientes con colelitiasis, colecistitis aguda y coledocolitiasis en el Seguro Social del Perú (EsSalud). Objetivo: Proveer recomendaciones clínicas basadas en evidencia para la evaluación y el manejo de pacientes con colelitiasis, colecistitis aguda y coledocolitiasis en EsSalud. Métodos: Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas en gastroenterología, cirujanos generales y metodólogos. El GEG formuló 10 preguntas clínicas a ser respondidas por la presente GPC. En septiembre del 2017 se realizaron búsquedas de revisiones sistemáticas y -cuando fue considerado pertinente- estudios primarios en PubMed. Se seleccionó la evidencia para responder 10 preguntas clínicas. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG usó la metodología GRADE para revisar la evidencia y formular las recomendaciones, los puntos de buenas prácticas clínicas y el flujograma de evaluación y manejo. Finalmente, la GPC fue aprobada con Resolución N° 021-IETSIESSALUD-2018. Resultados: La presente GPC abordó 10 preguntas clínicas sobre el diagnóstico y manejo de colelitiasis, colecistitis aguda y coledocolitiasis. En base a dichas preguntas se formularon 6 recomendaciones (5 recomendaciones condicionales y 1 recomendación fuerte), 17 puntos de buena práctica clínica y 3 flujogramas. Conclusión: El presente artículo resume la metodología y las conclusiones de la GPC basadas en evidencias para el diagnóstico y tratamiento de la colelitiasis, colecistitis aguda y coledocolitiasis de EsSalud.

ABSTRACT Introduction: This article summarizes the clinical practice guide (CPG) for the diagnosis and management of cholelithiasis, acute cholecystitis and choledocholithiasis in the Peruvian Social Security (EsSalud). Objective: To provide clinical recommendations based on evidence for the management of patients with cholelithiasis, acute cholecystitis and choledocholithiasis in EsSalud. Methods: a guideline task force (GTF) was formed with internists, general surgeons, gastroenterologists, and methodologists. The group proposed 10 clinical questions to be answered in this Clinical practice guideline (CPG). Systematic searches of preview reviews were performed and when it was necessary, primary studies from PubMed and CENTRAL during 2017 were reviewed. The evidence was selected aiming to answer each proposed question. Certainty of evidence was evaluated using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodical work sessions, the group used GRADE methodology for reviewing the evidence and formulating recommendations, good clinical practice items and three flowcharts for diagnosis and treatment. Finally, the CPG was approved by Resolution Nº 046-IETSI-ESSALUD-2017. Results: This CPG approached 10 clinical questions divided into two topics: diagnosis and management. Based on these questions; one strong recommendation, five weak recommendations, and 17 good clinical practice items and three flowcharts were formulated. Conclusion: This paper abstracts the methodology and evidence-based conclusions of the CPG for diagnosis and management of cholelithiasis, acute cholecystitis and choledocholithiasis in EsSalud.

Guía de práctica clínica para la prevención, diagnóstico y manejo de infecciones asociadas al acceso de hemodiálisis en el Seguro Social de Salud del Perú (EsSalud) / Clinical practice guidelines for the prevention, diagnosis and management of infections related with hemodialysis access of the Peruvian Health Social Security (EsSalud)

Introducción: El presente artículo resume la guía de práctica clínica (GPC) para la prevención, diagnóstico y manejo de infecciones asociadas al acceso de hemodiálisis en el Seguro Social del Perú (EsSalud). Objetivo: Proveer recomendaciones clínicas basadas en evidencia para la prevención, diagnóstico y tratamiento de infecciones asociadas al acceso de hemodiálisis en EsSalud. Material y Métodos: Se conformó un grupo elaborador de la guía (GEG) que incluyó especialistas y metodólogos. El GEG formuló 7 preguntas clínicas. Se realizó búsquedas sistemáticas de revisiones sistemáticas y estudios primarios en PubMed y CENTRAL de Cochrane entre noviembre del 2019 y marzo del 2020. Se seleccionó la evidencia para responder a las preguntas clínicas planteadas. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). El GEG usó la metodología GRADE para revisar la evidencia y formular recomendaciones, los puntos de buena práctica clínica y el flujograma de tratamiento. Finalmente, la GPC fue aprobada con Resolución N° 116-IETSI-ESSALUD-2020. Resultados: La presente GPC abordó 7 preguntas clínicas, divididas en tres temas: tamizaje, diagnóstico, estadiaje y tratamiento. En base a estas preguntas se formularon 12 recomendaciones (11 fuertes y 1 condicional), 33 puntos de buena práctica clínica y 2 flujogramas de manejo. Conclusión: El presente artículo resume la metodología y las conclusiones basadas en evidencias de la GPC para la prevención, diagnóstico y tratamiento de infecciones asociadas al acceso de hemodiálisis en EsSalud.

Background: This article summarizes the clinical practice guidelines (CPG) for the prevention, diagnosis and management of infections associated with hemodialysis access of the Peruvian Health Social Security (EsSalud). To provide clinical Objective: recommendations based on evidence for the prevention, diagnosis and management of infections associated with hemodialysis access in EsSalud. Aguideline development Material and Methods:group (GDG) was established, including medical specialists and methodologists. The GDG formulated 7 clinical questions to be answered in this CPG. Systematic searches of systematic reviews and primary studies (when pertinent) were conducted in PubMed, and CENTRAL(Cochrane) from November 2019 to March 2020. The evidence was selected to answer each of the clinical questions. The accuracy of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation(GRADE) methodology. In periodic work meetings, the GEG used the GRADE methodology to review the evidence and formulate the recommendations, the points of good clinical practice and the treatment flow chart. Finally, the CPG was approved with Resolution No. 116-IETSI-ESSALUD-2020. The present Results:CPG addressed 7 clinical questions of four topics: prevention, diagnosisandtreatment.Basedonthesequestions,12 recommendations (11strongrecommendationsand1weak recommendation), 33 points of good clinical practice, and 2 flowcharts were formulated. This paper summarizes Conclusion:the methodology and evidence-based conclusions from the CPG for the prevention, diagnosis and management of infections associated with hemodialysis access of EsSalud

Evaluación de la adherencia de Guías de Práctica Clínica en el Seguro Social del Perú / Clinical Practice Guidelines Adherence Evaluation

Según la OMS, las guías son un conjunto de "recomendaciones cuyo fin es ayudar a que los usuarios puedan tomar decisiones bien fundadas sobre la conveniencia de realizar intervenciones específicas, ensayos clínicos o tomar medidas en materia de salud pública, y dónde y cuándo hacerlo. Las recomendaciones también ayudan a los usuarios a seleccionar y priorizar entre una serie de posibles intervenciones". Existen diferentes tipos de guías; sin embargo, las usadas como apoyo a la toma de decisiones se denominan guías basadas en evidencia, se desarrollan a través de una metodología rigurosa basada en revisiones sistemáticas de la literatura conocida como metodología GRADE.

Guía de práctica clínica para diagnóstico y tratamiento de Hemofilia en el Seguro Social del Perú (EsSalud) / Clinical practice guideline for diagnosis and treatment of Hemophilia in the Peruvian Social Security (EsSalud)

Introducción: El presente artículo resume la guía de práctica clínica (GPC) para diagnóstico y tratamiento de hemofilia en el Seguro Social del Perú (EsSalud). Objetivo: Proveer recomendaciones clínicas basadas en evidencia para el diagnóstico y tratamiento de la hemofilia en EsSalud. Material y Métodos: Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos, el cual formuló preguntas clínicas. Se realizaron búsquedas sistemáticas de revisiones sistemáticas y ­cuando fue considerado pertinente­ estudios primarios en PubMed durante el 2020 y 2021. Se seleccionó la evidencia para responder cada una de las preguntas clínicasformuladas. Se evaluó la certeza de la evidencia usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG usó la metodología GRADE para revisar la evidencia y formular las recomendaciones. La GPC fue revisada por expertos externos previa a su aprobación. Resultados: La GPC abordó 09 preguntas clínicas de diagnóstico y tratamiento. En base a dichas preguntas se formularon 05 recomendaciones (01 fuerte y 04 condicionales), 51 puntos de buena práctica clínica, y 02 flujogramas. Conclusión: Se emitieron recomendaciones basadas en evidencia para el diagnóstico y tratamiento de personas con hemofilia.

Introduction: This article summarizes the clinical practice guideline (CPG) for diagnosis and treatment of hemophilia in the Social Security of Peru (EsSalud). Objective: To provide evidence-based clinical recommendations for the diagnosis and treatment of hemophilia in EsSalud. Material and Methods: A guideline development group (GDG) was formed, including medical specialists and methodologists, which formulated clinical questions. Systematic searches of systematic reviews and -when considered relevant- primary studies were performed in PubMed during 2020 and 2021. Evidence was selected to answer each of the clinical questions formulated. The certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic working meetings, the GEG used the GRADE methodology to review the evidence and formulate recommendations. The CPG was reviewed by external experts prior to approval. Results: The CPG addressed 09 clinical diagnostic and treatment questions. Based on these questions, 05 recommendations (01 strong and 04 conditional), 51 points of good clinical practice, and 02 flowcharts were formulated. Conclusion: Evidence-based recommendations were issued for the diagnosis and treatment of persons with hemophilia.

Guía de práctica clínica para el tamizaje, diagnóstico y tratamiento inicial de cáncer de próstata localizado y localmente avanzado en el Seguro Social del Perú (EsSalud) / Clinical practice guideline for screening, diagnosis and initial treatment of localized and locally advanced prostate cancer in the Peruvian Social Security (EsSalud)

Introducción: El presente artículo resume la guía de práctica clínica (GPC) para el tamizaje, diagnóstico, y tratamiento inicial del cáncer de próstata localizado y localmente avanzado en el Seguro Social del Perú (EsSalud). Objetivo: Proveer recomendaciones clínicas basadas en evidencia para el tamizaje, diagnóstico, y tratamiento inicial de adultos con cáncer de próstata localizado y localmente avanzado en EsSalud. Material y Métodos: Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos, el cual formuló preguntas clínicas. Se realizaron búsquedas sistemáticas de revisiones sistemáticas y ­cuando fue considerado pertinente­ estudios primarios en PubMed durante el 2020 y 2021. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas. Se evaluó la certeza de evidencia usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG usó la metodología GRADE para revisar la evidencia y formular las recomendaciones. La GPC fue revisada por expertos externos antes de su aprobación. Resultados: La GPC abordó 06 preguntas clínicas, divididas en 03 temas: tamizaje, diagnóstico, y tratamiento inicial. En base a dichas preguntas se formularon 08 recomendaciones (04 fuertes y 04 condicionales), 10 puntos de buena práctica clínica, y 04 flujogramas. Conclusión: Se emitieron recomendaciones basadas en evidencia para el manejo de pacientes con esta patología.

Background:This article summarizes the clinical practice guide (CPG) for the screening, diagnosis, and initial treatment of localized and locally advanced prostate cancer in the Social Security of Peru (EsSalud). To provide evidence-Objective:based clinical recommendations for the screening, diagnosis, and initial treatment of adults with localized and locally advanced prostate cancer in EsSalud. Methods: Aguideline developmentgroup(GDG)wasformed,whichincluded specialist physicians and methodologists, who formulated clinical questions. Systematic searches of systematic reviews were conducted and - when deemed relevant - primary studies in PubMed during 2020 and 2021. Evidence was selected to answer each of the proposed clinical questions. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic working meetings, the GEG used the GRADE methodology to review the evidence and formulate recommendations. The CPG was reviewed by external experts before its approval. The CPG Results: addressed 06 clinical questions, divided into 03 topics: screening, diagnosis, and initial treatment. Based on these questions, 08 recommendations were formulated (04 strong and 04 conditional), 10 points of good clinical practice, and 04 flow charts. Conclusion: Evidence-based recommendations were issued for the management of patients with this pathology

Guía de práctica clínica para el diagnóstico y manejo inicial de artritis reumatoide en el Seguro Social del Perú (EsSalud) / Clinical Practice Guideline for the diagnosis and initial management of Rheumatoid Arthritis in the Social Security of Peru (EsSalud)

La Artritis Reumatoide (AR) tiene adversas consecuencias en la salud su diagnóstico temprano y manejo óptimo requiere recomendaciones basadas en evidencia de alta calidad adaptadas a cada sistema de salud. Objetivo: Proveer recomendaciones clínicas basadas en evidencia para el diagnóstico y manejo inicial de la AR. Material y Métodos: Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos. El GEG formuló 10 preguntas clínicas a ser respondidas por la presente GPC. Se realizaron búsquedas sistemáticas de la evidencia publicada en PubMed y CENTRAL entre diciembre 2017 a julio 2019 (revisiones sistemáticas y ­cuando fue considerado pertinente­ estudios primarios). Se seleccionó la evidencia de mayor calidad para responder cada una de las preguntas clínicas planteadas. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE) y en reuniones de trabajo periódicas, el GEG usó dicha metodología para revisar la evidencia y formular las recomendaciones, los puntos de buena práctica clínica y los flujogramas. Finalmente, la GPC fue aprobada con Resolución N° 132 ­ IETSI ­ ESSALUD ­ 2019. Resultados: La presente GPC abordó 10 preguntas clínicas, divididas en dos temas: diagnóstico y manejo. En base a dichas preguntas se formularon 16 recomendaciones (5 fuertes y 11 condicionales), 45 puntos de buena práctica clínica, y 3 flujogramas. Conclusión: El presente artículo resume la metodología y las conclusiones basadas en evidencias de la GPC para el diagnóstico y manejo inicial de la AR en EsSalud.

Rheumatoid arthritis (RA) has adverse health consequences its early diagnosis and optimal management requires high quality evidence-based recommendations tailored to each health system. Objective: To provide evidence-based clinical recommendations for the diagnosis and initial management of RA. Material and Methods: A guideline development group (GDG) was formed that included medical specialists and methodologists. The GEG formulated 10 clinical questions to be answered by this CPG. Systematic searches of the evidence published in PubMed and CENTRAL were performed between December 2017 and July 2019 (systematic reviews and -when considered relevant- primary studies). The highest quality evidence was selected to answer each of the clinical questions posed. The certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, and in periodic working meetings, the GEG used this methodology to review the evidence and formulate the recommendations, good clinical practice points, and flowcharts. Finally, the CPG was approved by Resolution No. 132 - IETSI - ESSALUD - 2019. Results: This CPG addressed 10 clinical questions, divided into two topics: diagnosis and management. Based on these questions, 16 recommendations (5 strong and 11 conditional), 45 points of good clinical practice, and 3 flowcharts were formulated. Conclusion: This article summarizes the methodology and evidence-based conclusions of the CPG for the diagnosis and initial management of RA in EsSalud.

Guía de práctica clínica para el manejo de cáncer de cuello uterino estadios tempranos / Clinical practice guideline for the management of early-stage cervical cancer

Introducción: Este artículo resume la guía de práctica clínica (GPC) para el manejo de cáncer de cuello uterino estadios tempranos (IA1, IA2, IB1, IB2 o IIA1) en el Seguro Social del Perú (EsSalud). Objetivo: Proveer recomendaciones clínicas basadas en evidencia para el manejo de cáncer de cuello uterino estadios tempranos en EsSalud. Material y métodos: Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos. El GEG formuló 8 preguntas clínicas a ser respondidas por la presente GPC. Se realizó búsquedas sistemáticas de revisiones sistemáticas y ­cuando fue considerado pertinente­ estudios primarios en Pubmed, Embase y CENTRAL durante el 2017 - 2018. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG usó la metodología GRADE para revisar la evidencia y formular las recomendaciones, los puntos de buenas prácticas clínicas y los flujogramas de manejo. Finalmente, la GPC fue aprobada con Resolución N° 27-IETSI-ESSALUD-2020. Resultados: La presente GPC abordó 8 preguntas clínicas abordando el manejo del cáncer de cuello uterino en estadios tempranos. En base a dichas preguntas se formularon 10 recomendaciones (2 recomendaciones fuertes y 8 recomendaciones condicionales), 7 puntos de buena práctica clínica, y 4 flujogramas. Conclusión: El presente artículo resume la metodología y las conclusiones basadas en evidencias de la GPC para el manejo del cáncer de cuello uterino en estadios tempranos en EsSalud.

Introduction: This article summarizes the clinical practice guideline (CPG) for the management of early stage cervical cancer (IA1, IA2, IB1, IB2 or IIA1) in the Social Security of Peru (EsSalud). Objective: To provide evidence-based clinical recommendations for the management of early stage cervical cancer in EsSalud. Material and methods: A guideline development group (GEG) was formed that included medical specialists and methodologists. The GEG formulated 8 clinical questions to be answered by this CPG. Systematic searches of systematic reviews and -when considered relevant- primary studies were performed in Pubmed, Embase and CENTRAL during 2017 - 2018. Evidence was selected to answer each of the clinical questions posed. The certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic working meetings, the GEG used the GRADE methodology to review the evidence and formulate recommendations, good clinical practice points, and management flowcharts. Finally, the CPG was approved by Resolution No. 27-IETSI-ESSALUD-2020. Results: This CPG addressed 8 clinical questions on the management of early stage cervical cancer. Based on these questions, 10 recommendations were formulated (2 strong recommendations and 8 conditional recommendations), 7 points of good clinical practice, and 4 flowcharts. Conclusion: This article summarizes the methodology and evidence-based conclusions of the CPG for the management of early stage cervical cancer in EsSalud.

Guía de práctica clínica para el tratamiento farmacológico inicial de nefritis lúpica en el Seguro Social del Perú (EsSalud) / Clinical practice guideline for the initial pharmacological treatment of lupus nephritis in the Peruvian Social Security (EsSalud)

Introducción: El presente artículo resume la guía de práctica clínica (GPC) para el tratamiento farmacológico inicial nefritis lúpica en el Seguro Social del Perú (EsSalud). Objetivo: Proveer recomendaciones clínicas basadas en evidencia para tratamiento farmacológico inicial de adultos con nefritis lúpica clase I a V no refractarios en EsSalud. Material y Métodos: Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos, el cual formuló preguntas clínicas. Se realizaron búsquedas sistemáticas de revisiones sistemáticas y ­cuando fue considerado pertinente­ estudios primarios en PubMed durante el 2021. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas. Se evaluó la certeza de evidencia usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG usó la metodología GRADE para revisar la evidencia y formular las recomendaciones. La GPC fue revisada por expertos externos antes de su aprobación. Resultados: La GPC abordó 6 preguntas clínicas, divididas en 2 temas: tratamiento inicial de la fase de inducción y mantenimiento. En base a dichas preguntas se formularon 11 recomendaciones (todas condicionales), 22 puntos de buena práctica clínica, y 2 flujogramas. Conclusión: Se emitieron recomendaciones basadas en evidencia para el manejo de pacientes con esta patología.

Introduction: This article summarizes the clinical practice guideline (CPG) for initial pharmacological treatment of lupus nephritis in the Peruvian Social Security (EsSalud). Objective: To provide evidence-based clinical recommendations for initial pharmacological treatment of adults with non-refractory class I to V lupus nephritis in EsSalud. Material and Methods: A guideline development group (GDG) was formed that included medical specialists and methodologists, which formulated clinical questions. Systematic searches of systematic reviews and -when considered pertinent- primary studies were performed in PubMed during 2021. Evidence was selected to answer each of the clinical questions posed. The certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic working meetings, the GEG used the GRADE methodology to review the evidence and formulate recommendations. The CPG was reviewed by external experts before approval. Results: The CPG addressed 6 clinical questions, divided into 2 topics: initial treatment of the induction phase and maintenance. Based on these questions, 11 recommendations (all conditional), 22 points of good clinical practice, and 2 flowcharts were formulated. Conclusion: Evidence-based recommendations were issued for the management of patients with this pathology.

Guía de práctica clínica para el tamizaje, diagnóstico y manejo de la enfermedad renal crónica en estadios 1 al 3 en el Seguro Social del Perú (EsSalud) / Clinical practice guideline for the screening, diagnosis, and management of chronic kidney disease stages 1-3 for the Peruvian Social Security (EsSalud)

RESUMEN El presente artículo resume la guía de práctica clínica (GPC) para tamizaje, diagnóstico y manejo de los pacientes con enfermedad renal crónica (ERC) en los estadios 1 al 3 en el Seguro Social del Perú (EsSalud). Para el desarrollo de esta GPC, se conformó un grupo elaborador de la guía (GEG) que incluyó especialistas clínicos y metodólogos, el cual formuló ocho preguntas clínicas. Para responder cada pregunta se realizaron búsquedas sistemáticas de revisiones sistemáticas y, cuando fue considerado pertinente, de estudios primarios; y se seleccionó la evidencia pertinente. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones periódicas, el GEG usó la metodología GRADE para revisar la evidencia y emitir las recomendaciones. Se emitieron ocho recomendaciones (cuatro fuertes y cuatro condicionales), 29 puntos de buena práctica clínica, y tres flujogramas.

ABSTRACT This paper summarizes the clinical practice guidelines (CPG) for the screening, diagnosis, and management of patients with chronic kidney disease (CKD) stages 1-3 in the Social Security of Peru (EsSalud). A guideline development group (GDG) was established for develop this CPG, which included clinical and methodology specialists, who formulated 08 clinical questions. Systematic searches of systematic reviews and, when considered necessary, primary studies were conducted to answer each question; and relevant evidence was selected. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic work meetings, the GDG used the GRADE methodology for reviewing the evidence and for developing recommendations. At the end, this CPG formulated 08 recommendations (04 strong and 04 conditional), 29 points of good clinical practice, and 03 flowcharts were formulated.

Molecular diversity of the developing and adult myocardium: implications for tissue targeting.

The heart is the first functional embryonic organ. During embryogenesis the development of the heart and its vasculature is a complex process that give rise to the formation of four-chambered heart with a synchronously contraction, from a single tubular heart with a peristaltic contraction. The spectacular progress of modern developmental biology has marked the beginning of a new era in embryology. Over the last years, several families of genes with restricted cardiac expression have been identified including genes such as those encoding for tissue-specific transcription factors, contractile proteins, as well as, more recently, ion channels. In this review, we illustrate the heterogeneity of the developing and adult myocardium in mice. Looking at the expression profile of transcription factors and contractile proteins, it can be seen that the tubular heart is patterned along the three embryonic axes, antero/posterior, dorso/ventral and left/right, besides having several genes that are expressed homogeneously within the entire myocardium. In the embryonic heart, two new types of pattern arise, chamber-specific and systemic/pulmonary gene expression, while within the foetal and adult heart, a wider heterogeneity is observed, not only between the working myocardium and the specialized cardiac conduction system but also within distinct myocardial chambers, specially in the atrial components. Such heterogeneity is also observed if one looks at the electrophysiological characteristics of the developing myocardium and their underlying molecular components. Several evidences support the notion that the distinct expression profiles observed in mice can be extrapolated to humans. Thus, these data reveal that the molecular diversity of the myocardium should be taken into account on the design of drug targets as well as on gene and cell therapy approaches.

Adipose mesenchymal stromal cells isolated from type 2 diabetic patients display reduced fibrinolytic activity.

Stem cells have been successfully used for the treatment of critical limb ischemia (CLI). We conducted a clinical trial to determine the feasibility of using autologous adipose-derived mesenchymal stromal cells (AdMSCs) for the treatment of CLI. Unexpectedly, two diabetic patients developed peripheral microthrombosis. This adverse effect, which contrasts with the reported antithrombotic properties of MSCs, may stem from the diabetic environment that alters the fibrinolytic activity of AdMSCs, thereby increasing the probability of developing thrombosis. Here, we confirm this premise by demonstrating that diabetic AdMSCs cultured in the presence of blood sera expressed and released higher levels of plasminogen activator inhibitor type 1, reduced levels of tissue plasminogen activator, and lower d-dimer formation compared with nondiabetic AdMSCs. Thus, to establish an appropriate cell therapy for diabetic patients, we recommend including new preclinical safety tests, such as the d-dimer and/or the tissue plasminogen activator-to-plasminogen activator inhibitor type 1 ratio tests, to assess fibrinolytic activity of cells before implantation.