Response predictors to cardiac resynchronization therapy in chronic heart failure: a 10-year-cardiovascular center experience.

BACKGROUND: Cardiac resynchronization therapy (CRT) has been established as an effective therapy for heart failure with reduced ejection fraction. Randomized clinical trials have shown its impact on mortality and HF hospitalizations, as well as improvement of symptoms and quality of life. OBJECTIVES: Finding clinical, electrocardiographic, and echocardiographic variables that may predict the response to cardiac resynchronization therapy (CRT). METHODS: We performed a single-center, observational, analytic, and retrospective study that included 102 patients with heart failure (HF) diagnosis who underwent CRT according to guideline-directed therapy from January 2010 to April 2020 in a third-level center. CRT response was defined as an improvement of New York Heart Association functional class in at least 1 category associated with a recovery of ≥ 5% in the left ventricular ejection fraction (LVEF). RESULTS: Our study population was 102 patients of which 61 (59.8%) were men. The mean age at HF diagnosis was 54 ± 18.7 years. Ischemic heart disease was the etiology in 37 (36.3%) cases. Fifty-one (50%) patients were classified as responders. Responders had wider QRS, and lower LVEF and right ventricular fractional area change at baseline. After CRT, responders had a greater reduction of QRS duration, and improvement in LVEF, global longitudinal strain, and echocardiographic dyssynchrony parameters. Multivariate regression analysis showed that left bundle branch block (LBBB), left ventricular end-diastolic volume (LVEDV), tricuspid annular plane systolic excursion (TAPSE), and baseline difference of pre-ejection periods were predictors of a positive response to CRT in this population. CONCLUSIONS: LBBB, TAPSE, LVEDV, and pre-ejection time difference are independent variables that can predict adequate response to CRT.

ANTECEDENTES: La terapia de resincronización cardíaca (TRC) se ha establecido como una terapia efectiva para la insuficiencia cardíaca con fracción de eyección reducida. Ensayos clínicos aleatorizados han demostrado su impacto en la mortalidad y hospitalizaciones por insuficiencia cardíaca, así como la mejora de los síntomas y la calidad de vida. OBJETIVOS: Determinar las variables clínicas, electrocardiográficas y ecocardiográficas que puedan predecir la respuesta a la terapia de resincronización cardíaca (TRC). MÉTODO: Estudio unicéntrico, observacional, analítico, retrospectivo, que incluyó 102 pacientes con diagnóstico de IC sometidos a TRC y terapia dirigida por guías, de enero de 2010 a abril de 2020, en un centro de tercer nivel. La respuesta a TRC fue definida como mejoría de la clase funcional de la New York Heart Association en al menos 1 categoría, asociado con una recuperación ≥ 5% en la fracción de expulsión del ventrículo izquierdo (FEVI). RESULTADOS: Incluimos a 102 pacientes, 61 (59.8%) fueron hombres. El promedio de edad al diagnóstico de IC fue 54 ± 18.7 años. La cardiopatía isquémica fue la etiología en 37 (36.3%) pacientes. 51 (50%) pacientes, fueron clasificados como respondedores. Los respondedores presentaron QRS amplio, menor FEVI y menor fracción de acortamiento del ventrículo derecho al inicio del estudio. Después de la TRC, los respondedores tuvieron una mayor reducción en la duración del QRS, mejoría en la FEVI, strain longitudinal global y parámetros de disincronía ecocardiográfica. El análisis de regresión multivariado mostró que el bloqueo de rama izquierdo (BRI), el volumen telediastólico del ventrículo izquierdo (VTDVI) la excursión sistólica del plano anular tricuspídeo (TAPSE) y la diferencia basal del período expulsivo fueron predictores de respuesta positiva a TRC. CONCLUSIONES: BRI, TAPSE, VTDVI y la diferencia basal de períodos preexpulsivos son variables independientes que predicen respuesta adecuada a TRC.

User-experience testing of an evidence-to-decision framework for selecting essential medicines.

Essential medicine lists (EMLs) are important medicine prioritization tools used by the World Health Organization (WHO) EML and over 130 countries. The criteria used by WHO's Expert Committee on the Selection and Use of Essential Medicines has parallels to the GRADE Evidence-to-Decision (EtD) frameworks. In this study, we explored the EtD frameworks and a visual abstract as adjunctive tools to strengthen the integrate evidence and improve the transparency of decisions of EML applications. We conducted user-experience testing interviews of key EML stakeholders using Morville's honeycomb model. Interviews explored multifaceted dimensions (e.g., usability) on two EML applications for the 2021 WHO EML-long-acting insulin analogues for diabetes and immune checkpoint inhibitors for lung cancer. Using a pre-determined coding framework and thematic analysis we iteratively improved both the EtD framework and the visual abstract. We coded the transcripts of 17 interviews with 13 respondents in 103 locations of the interview texts across all dimensions of the user-experience honeycomb. Respondents felt the EtD framework and visual abstract presented complementary useful and findable adjuncts to the traditional EML application. They felt this would increase transparency and efficiency in evidence assessed by EML committees. As EtD frameworks are also used in health practice guidelines, including those by the WHO, respondents articulated that the adoption of the EtD by EML applications represents a tangible mechanism to align EMLs and guidelines, decrease duplication of work and improve coordination. Improvements were made to clarify instructions for the EtD and visual abstract, and to refine the design and content included. 'Availability' was added as an additional criterion for EML applications to highlight this criterion in alignment with WHO EML criteria. EtD frameworks and visual abstracts present additional important tools to communicate evidence and support decision-criteria in EML applications, which have global health impact. Access to essential medicines is important for achieving universal health coverage, and the development of essential medicine lists should be as evidence-based and trustworthy as possible.

Revisiting Classical Controller Design and Tuning with Genetic Programming.

This paper introduces the application of a genetic programming (GP)-based method for the automated design and tuning of process controllers, representing a noteworthy advancement in artificial intelligence (AI) within the realm of control engineering. In contrast to already existing work, our GP-based approach operates exclusively in the time domain, incorporating differential operations such as derivatives and integrals without necessitating intermediate inverse Laplace transformations. This unique feature not only simplifies the design process but also ensures the practical implementability of the generated controllers within physical systems. Notably, the GP's functional set extends beyond basic arithmetic operators to include a rich repertoire of mathematical operations, encompassing trigonometric, exponential, and logarithmic functions. This broad set of operations enhances the flexibility and adaptability of the GP-based approach in controller design. To rigorously assess the efficacy of our GP-based approach, we conducted an extensive series of tests to determine its limits and capabilities. In summary, our research establishes the GP-based approach as a promising solution for automating the controller design process, offering a transformative tool to address a spectrum of control problems across various engineering applications.

Observational analysis of clinical and pathological characteristics and their prognostic impact in Mexican patients with breast cancer: A multi-center study.

Breast cancer is the most incidental and deadly neoplasm worldwide; in Mexico, very few epidemiologic reports have analyzed the pathological features and its impact on their clinical outcome. Here, we studied the relation between pathological features and the clinical presentation at diagnosis and their impact on the overall and progression-free survival of patients with breast cancer. For this purpose, we collected 199 clinical records of female patients, aged at least 18 years old (y/o), with breast cancer diagnosis confirmed by biopsy. We excluded patients with incomplete or conflicting clinical records. Afterward, we performed an analysis of overall and progression-free survival and associated risks. Our results showed an average age at diagnosis of 52 y/o (24-85), the most common features were: upper outer quadrant tumor (32%), invasive ductal carcinoma (76.8%), moderately differentiated (44.3%), early clinical stages (40.8%), asymptomatic patients (47.8%), luminal A subtype (47.8%). Median overall survival was not reached, but median progression-free survival was 32.2 months (29.75-34.64, CI 95%) associated risk were: clinical stage (p < 0.0001) symptomatic presentation (p = 0.009) and histologic grade (p = 0.02). Therefore, we concluded that symptom presence at diagnosis impacts progression-free survival, and palpable symptoms are related to an increased risk for mortality.

Non-reperfused ST-elevation myocardial infarction: notions from a low-to-middle-income country / Infarto de miocardio con elevación del ST no reperfundido: nociones de un país de ingresos bajos a medios

Abstract Objective: The objective of the study was to analyze the differences between survivors and non-survivors with non-reperfused ST-segment elevation myocardial infarction (STEMI) and to identify the predictors of in-hospital mortality. Methods: A retrospective cohort study included non-reperfused STEMI patients from October 2005 to August 2020. Patients were classified into survivors and non-survivors. We compared patient characteristics, treatments, and outcomes among the groups and identified factors associated with in-hospital mortality. Results: We included 2442 patients with non-reperfused STEMI and we found a mortality of 12.7% versus 7.2% in reperfused STEMI. The main reason for non-reperfusion was delayed presentation (96.1%). Non-survivors were older, more often women, and had diabetes, hypertension, or atrial fibrillation. The left main coronary disease was more frequent in non-survivors as well as three-vessel disease. Non-survivors developed more in-hospital heart failure, reinfarction, atrioventricular block, bleeding, stroke, and death. The main predictors for in-hospital mortality were renal dysfunction (HR 3.41), systolic blood pressure < 100 mmHg (HR 2.26), and left ventricle ejection fraction < 40% (HR 1.97). Conclusion: Mortality and adverse outcomes occur more frequently in non-reperfused STEMI. Non-survivors tend to be older, with more comorbidities, and have more adverse in-hospital outcomes.

Resumen Objetivo: Analizar las diferencias entre los sobrevivientes y no sobrevivientes con infarto agudo de miocardio no reperfundido y conocer los predictores de mortalidad intrahospitalaria. Métodos: Estudio de cohorte retrospectiva que incluyó pacientes con infarto agudo de miocardio no reperfundido de octubre de 2005 a agosto de 2020. Se clasificaron los pacientes de acuerdo a su estado de sobrevida y se compararon las características clínicas, tratamientos y desenlaces para poder identificar los predictores de mortalidad intrahospitalaria. Resultados: Se incluyeron 2442 pacientes con infarto agudo de miocardio no reperfundido, en los que se encontró una mortalidad de 12.7% vs 7.2% los que si recibieron tratamiento de reperfusión. La principal razón para no recibir tratamiento de reperfusión fue el retraso en la atención médica (96.1%). Los no sobrevivientes tuvieron mayor edad, fueron mujeres y tuvieron mayor frecuencia de diabetes, hipertensión y fibrilación atrial. El tronco de la coronaria izquierda y la enfermedad trivascular fueron más frecuentes en los que no sobrevivieron. Los pacientes que no sobrevivieron desarrollaron más insuficiencia cardiaca, reinfarto, bloqueo atrioventricular, sangrados, evento vascular cerebral y muerte. Los principales predictores de mortalidad intrahospitalaria fueron: insuficiencia renal (HR 3.41), tensión arterial sistólica al ingreso < 100 mmHg (HR 2.26) y fracción de eyección del ventrículo izquierdo < 40% (HR 1.97). Conclusiones: Los pacientes con infarto de miocardio no reperfundido tienen mayor mortalidad y desenlaces adversos. Los no sobrevivientes fueron mayores, con más comorbilidades y desarrollaron más desenlaces adversos intrahospitalarios.

Non-reperfused ST-elevation myocardial infarction: notions from a low-to-middle-income country.

OBJECTIVE: The objective of the study was to analyze the differences between survivors and non-survivors with non-reperfused ST-segment elevation myocardial infarction (STEMI) and to identify the predictors of in-hospital mortality. METHODS: A retrospective cohort study included non-reperfused STEMI patients from October 2005 to August 2020. Patients were classified into survivors and non-survivors. We compared patient characteristics, treatments, and outcomes among the groups and identified factors associated with in-hospital mortality. RESULTS: We included 2442 patients with non-reperfused STEMI and we found a mortality of 12.7% versus 7.2% in reperfused STEMI. The main reason for non-reperfusion was delayed presentation (96.1%). Non-survivors were older, more often women, and had diabetes, hypertension, or atrial fibrillation. The left main coronary disease was more frequent in non-survivors as well as three-vessel disease. Non-survivors developed more in-hospital heart failure, reinfarction, atrioventricular block, bleeding, stroke, and death. The main predictors for in-hospital mortality were renal dysfunction (HR 3.41), systolic blood pressure < 100 mmHg (HR 2.26), and left ventricle ejection fraction < 40% (HR 1.97). CONCLUSION: Mortality and adverse outcomes occur more frequently in non-reperfused STEMI. Non-survivors tend to be older, with more comorbidities, and have more adverse in-hospital outcomes.

OBJETIVO: Analizar las diferencias entre los sobrevivientes y no sobrevivientes con infarto agudo de miocardio no reperfundido y conocer los predictores de mortalidad intrahospitalaria. MÉTODOS: Estudio de cohorte retrospectiva que incluyó pacientes con infarto agudo de miocardio no reperfundido de octubre de 2005 a agosto de 2020. Se clasificaron los pacientes de acuerdo a su estado de sobrevida y se compararon las características clínicas, tratamientos y desenlaces para poder identificar los predictores de mortalidad intrahospitalaria. RESULTADOS: Se incluyeron 2442 pacientes con infarto agudo de miocardio no reperfundido, en los que se encontró una mortalidad de 12.7% vs 7.2% los que si recibieron tratamiento de reperfusión. La principal razón para no recibir tratamiento de reperfusión fue el retraso en la atención médica (96.1%). Los no sobrevivientes tuvieron mayor edad, fueron mujeres y tuvieron mayor frecuencia de diabetes, hipertensión y fibrilación atrial. El tronco de la coronaria izquierda y la enfermedad trivascular fueron más frecuentes en los que no sobrevivieron. Los pacientes que no sobrevivieron desarrollaron más insuficiencia cardiaca, reinfarto, bloqueo atrioventricular, sangrados, evento vascular cerebral y muerte. Los principales predictores de mortalidad intrahospitalaria fueron: insuficiencia renal (HR 3.41), tensión arterial sistólica al ingreso < 100 mmHg (HR 2.26) y fracción de eyección del ventrículo izquierdo < 40% (HR 1.97). CONCLUSIONES: Los pacientes con infarto de miocardio no reperfundido tienen mayor mortalidad y desenlaces adversos. Los no sobrevivientes fueron mayores, con más comorbilidades y desarrollaron más desenlaces adversos intrahospitalarios.

Update of the agency for healthcare research and quality guidance on using nonrandomized studies in evidence syntheses.

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A Generic Deep Learning Based Cough Analysis System From Clinically Validated Samples for Point-of-Need Covid-19 Test and Severity Levels.

In an attempt to reduce the infection rate of the COrona VIrus Disease-19 (Covid-19) countries around the world have echoed the exigency for an economical, accessible, point-of-need diagnostic test to identify Covid-19 carriers so that they (individuals who test positive) can be advised to self isolate rather than the entire community. Availability of a quick turn-around time diagnostic test would essentially mean that life, in general, can return to normality-at-large. In this regards, studies concurrent in time with ours have investigated different respiratory sounds, including cough, to recognise potential Covid-19 carriers. However, these studies lack clinical control and rely on Internet users confirming their test results in a web questionnaire (crowdsourcing) thus rendering their analysis inadequate. We seek to evaluate the detection performance of a primary screening tool of Covid-19 solely based on the cough sound from 8,380 clinically validated samples with laboratory molecular-test (2,339 Covid-19 positive and 6,041 Covid-19 negative) under quantitative RT-PCR (qRT-PCR) from certified laboratories. All collected samples were clinically labelled, i.e., Covid-19 positive or negative, according to the results in addition to the disease severity based on the qRT-PCR threshold cycle (Ct) and lymphocytes count from the patients. Our proposed generic method is an algorithm based on Empirical Mode Decomposition (EMD) for cough sound detection with subsequent classification based on a tensor of audio sonographs and deep artificial neural network classifier with convolutional layers called 'DeepCough'. Two different versions of DeepCough based on the number of tensor dimensions, i.e., DeepCough2D and DeepCough3D, have been investigated. These methods have been deployed in a multi-platform prototype web-app 'CoughDetect'. Covid-19 recognition results rates achieved a promising AUC (Area Under Curve) of [Formula: see text] 98 . 80 % ± 0 . 83 % , sensitivity of [Formula: see text] 96 . 43 % ± 1 . 85 % , and specificity of [Formula: see text] 96 . 20 % ± 1 . 74 % and average AUC of [Formula: see text] 81 . 08 % ± 5 . 05 % for the recognition of three severity levels. Our proposed web tool as a point-of-need primary diagnostic test for Covid-19 facilitates the rapid detection of the infection. We believe it has the potential to significantly hamper the Covid-19 pandemic across the world.

Concordance between Ki-67 index in invasive breast cancer and molecular signatures: EndoPredict and MammaPrint.

Identifying patients with hormone receptor-positive (HR+) early invasive breast cancer (EIBC) who benefit from adjuvant chemotherapy has improved with molecular signature tests. However, due to high cost and limited availability, alternative tests are used. The present study sought to evaluate the performance of the proliferation marker Ki-67 to identify these patients and explore its association with molecular signatures and risk stratification markers. From the San José TecSalud Hospital in Monterrey México, patients with HR+ EIBC as tested with EndoPredict or MammaPrint and Ki-67 index were identified. They were categorized into two groups: Group 1 (June 2016-August 2018) was evaluated using EndoPredict and Group 2 (June 2016-August 2018) with MammaPrint. A ≥20% Ki67 index cutoff was utilized to identify highly proliferative EIBC and an area under the receiver-operating characteristic curve and κ concordance were utilized to evaluate the performance of Ki-67 index compared to molecular signature tests. In the EndoPredict group, 54/96 patients were considered high-risk based on their EPclin score, while 57/96 patients had Ki-67 index ≥20%. However, there was no significant overall concordance between them (59.37%, κ=0.168, P=0.09), while the given risk of distant recurrence given in percentage by EPclin had a positive association with the Ki67 index (P=0.04). In the MammaPrint group, 21/70 patients were considered high-risk and 36/70 patients presented with a Ki-67 index ≥20% with a significant overall concordance (67.14%, κ=0.35, P<0.001). In addition, high Ki-67 index was associated with the Nottingham histological grade in both groups. In conclusion, there was a concordance between Ki-67 and MammaPrint risk stratification of HR+ EIBC and no concordance with the EndoPredict molecular signature, but a positive association with the given percentage of recurrence and the median Ki-67 index as the cutoff at our center. Cost-effectiveness analyses of these tests in developing countries are required; until then, the use of Ki-67 appears reasonable to aid clinical decisions, together with the other established clinicopathological variables.

Development and design validation of a novel network meta-analysis presentation tool for multiple outcomes: a qualitative descriptive study.

OBJECTIVE: The Grades of Recommendations, Assessment, Development and Evaluation working group recently developed an innovative approach to interpreting results from network meta-analyses (NMA) through minimally and partially contextualised methods; however, the optimal method for presenting results for multiple outcomes using this approach remains uncertain. We; therefore, developed and iteratively modified a presentation method that effectively summarises NMA results of multiple outcomes for clinicians using this new interpretation approach. DESIGN: Qualitative descriptive study. SETTING: A steering group of seven individuals with experience in NMA and design validation studies developed two colour-coded presentation formats for evaluation. Through an iterative process, we assessed the validity of both formats to maximise their clarity and ease of interpretation. PARTICIPANTS: 26 participants including 20 clinicians who routinely provide patient care, 3 research staff/research methodologists and 3 residents. MAIN OUTCOME MEASURES: Two team members used qualitative content analysis to independently analyse transcripts of all interviews. The steering group reviewed the analyses and responded with serial modifications of the presentation format. RESULTS: To ensure that readers could easily discern the benefits and safety of each included treatment across all assessed outcomes, participants primarily focused on simple information presentations, with intuitive organisational decisions and colour coding. Feedback ultimately resulted in two presentation versions, each preferred by a substantial group of participants, and development of a legend to facilitate interpretation. CONCLUSION: Iterative design validation facilitated the development of two novel formats for presenting minimally or partially contextualised NMA results for multiple outcomes. These presentation approaches appeal to audiences that include clinicians with limited familiarity with NMAs.

Pooling of cohort studies and RCTs affects GRADE certainty of evidence in nutrition research.

BACKGROUND: There is a little empirical evidence of the impact of pooling randomized controlled trials (RCTs) and cohort studies (CSs) on the certainty-of-evidence. To evaluate the hypothetical-scenario of pooling bodies-of-evidence from RCTs with matched bodies-of-evidence from CSs on the certainty-of-evidence. METHODS: We extracted GRADE ratings of bodies-of-evidence from RCTs in Cochrane reviews, and rated the certainty-of-evidence from matched bodies-of-evidence from CSs. We then evaluated the impact of pooling both bodies-of-evidence on the overall certainty-of-evidence, and on individual GRADE domains. RESULTS: Fourty-two pooled bodies-of-evidence were rated, ranging from very-low (bodies-of-evidenceRCTs: 9.5%; bodies-of-evidenceCSs: 40.5%; pooled-bodies-of-evidence: 0%) to low (bodies-of-evidenceRCTs: 38.1%; bodies-of-evidenceCSs: 45.2%; pooled-bodies-of-evidence: 19.1%), moderate (bodies-of-evidenceRCTs: 33.4%; bodies-of-evidenceCSs: 14.3%; pooled-bodies-of-evidence: 57.1%), and high (bodies-of-evidenceRCTs: 19%; bodies-of-evidenceCSs: 0%; pooled-bodies-of-evidence: 23.8%). Certainty-of-evidence was downgraded mostly for imprecision and risk of bias for bodies-of-evidence from RCTs, and for risk of bias and inconsistency for bodies-of-evidence from CSs. Pooling both bodies-of-evidence mitigates rating down for imprecision compared to bodies-of-evidence from RCTs and inconsistency compared to bodies-of-evidence from CSs. CONCLUSION: Our hypothetical study suggests that pooling both bodies-of-evidence would reduce the amount of very-low and low certainty-of-evidence ratings, but how to integrate RCTs and CSs and whether or not to pool these bodies-of-evidence requires proper guidance before systematic review authors or guideline developers should consider this approach.

A Methodological Framework for Assessing the Sustainability of Solid Biofuels Systems.

This paper introduces a methodological framework for assessing the sustainability of solid biofuels in Mexico. The designed framework comprises 13 normalized indicators and two diagnostic studies, covering the economic, social, environmental, and institutional sustainability dimensions, and their intersections. Indicators are normalized using the concept of load capacity of a system, similarly to the planetary boundaries. Thus, the graphical representation of results facilitates their multidimensional analysis. The framework was applied to three case studies: traditional fuelwood in rural households, charcoal for restaurant grilling, and electricity cogeneration from sugarcane bagasse. This was part of an iterative process of testing and refining the framework and simultaneously demonstrating its application in the Mexican bioenergy context. This led to the conclusion that the resulting framework (a) provides a useful, quantitative, and comprehensive overview of both broad and specific sustainability aspects of the assessed system; (b) requires a balance of accessible but also scattered or sensitive data, similarly to most existing frameworks; (c) is highly flexible and applicable to both modern and traditional solid biofuels; and (d) is simple to communicate and interpret for a wide audience. Key directions for improvement of the framework are also discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s12155-021-10365-2.

Molecular, Histological, and Clinical Characteristics of Oligodendrogliomas: A Multi-Institutional Retrospective Study.

BACKGROUND: Reports suggest that phosphatidylinositol 3-kinase pathway alterations confer increased risk of progression and poor prognosis in oligodendroglioma, IDH-mutant, and 1p/19q-codeleted molecular oligodendrogliomas (mODG). However, factors that affect prognosis in mODG have not been thoroughly studied. In addition, the benefits of adjuvant radiation and temozolomide (TMZ) in mODGs remain to be determined. OBJECTIVE: To evaluate the role of PIK3CA mutations in mODGs. METHODS: One hundred seven mODGs (2008-2019) diagnosed at 2 institutions were included. A retrospective review of clinical characteristics, molecular alterations, treatments, and outcomes was performed. RESULTS: The median age was 37 years, and 61 patients (57%) were male. There were 64 (60%) World Health Organization (WHO) grade 2 and 43 (40%) WHO grade 3 tumors. Eighty-two patients (77%) were stratified as high risk (age 40 years or older and/or subtotal resection per Radiation Treatment Oncology Group-9802). Gross-total resection was achieved in 47 patients (45%). Treatment strategies included observation (n = 15), TMZ (n = 11), radiation (n = 13), radiation/TMZ (n = 62), and others (n = 6). Our results show a benefit of TMZ vs observation in progression-free survival (PFS). No difference in PFS or overall survival (OS) was observed between radiation and radiation/TMZ. PIK3CA mutations were detected in 15 (14%) mODG, and shorter OS was observed in PIK3CA-mutant compared with PIK3CA wild-type mODGs (10.7 years vs 15.1 years, P = .009). WHO grade 3 tumors showed a shorter PFS, but no significant difference in OS was observed between WHO grades. CONCLUSION: Our findings suggest that mODGs harboring PIK3CA mutations have worse OS. Except for an advantage in PFS with TMZ treatment, adjuvant TMZ, radiation, or a combination of the two showed no significant improvement in OS.

[Consensus on the use of iSGLT2 in the treatment of patients with type 2 diabetes mellitus]. / Documento de consenso sobre el uso de los iSGLT2 en el tratamiento de pacientes con diabetes mellitus tipo 2.

Although in recent years in Mexico the quality of diabetes mellitus (DM) care has improved and access to health services and medications has increased, there is a lack of adherence to the recommendations of the clinical guidelines, which could explain the poor glycemic control in many of the patients with DM. Sodium-glucose cotransporter type 2 (iSGLT2) inhibitors have been the last class of antidiabetic agents to receive approval from the Food and Drug Administration (FDA) and COFEPRIS (Mexico). In order to improve the use of SGLT2i in clinical practice in Mexico, this paper presents the recommendations issued by a panel of eleven Mexican experts based on the new published evidence for the treatment of patients with DM2.

Aunque en los últimos años en México ha mejorado la calidad de la atención de la diabetes mellitus (DM) y ha aumentado el acceso a servicios de salud y medicamentos, existe una falta de apego a las recomendaciones de las guías de práctica clínica, que podría explicar la falta de un control glucémico adecuado en muchos de los pacientes con DM. Los inhibidores del cotransportador de sodio-glucosa tipo 2 (iSGLT2) han sido la última clase de agentes antidiabéticos en recibir la aprobación de la Food and Drug Administration (FDA) y de la Comisión Federal para la Protección contra Riesgos Sanitarios de México (COFEPRIS). Con el fin de mejorar el uso de los iSGLT2 en la práctica clínica en México, en este documento se presentan las recomendaciones emitidas por un panel de 11 expertos mexicanos con base en las nuevas evidencias publicadas para el tratamiento de los pacientes con DM2.

Bioactive compounds and hepatoprotective effect of Hancornia speciosa gomes fruit juice on acetaminophen-induced hepatotoxicity in vivo.

Hancornia speciosa Gomes (HS) is a Brazilian fruit tree used in inflammatory disorders by folk medicine. Here we sought to investigate the antioxidant and hepatoprotective properties of HS fruit juice in acetaminophen-induced hepatoxicity model in rats, as well as to perform a comprehensive chemical characterization of phenolics and metals by mass spectrometry. HS showed hepatoprotective and antioxidant activity by decreasing MDA and liver injury markers at healthy control levels. In addition, liver histopathological analysis revealed that HS decreases hepatocellular degeneration. Chemical characterization revealed 16 different phenolics, being chlorogenic acid (150 ± 5 µg/g) and rutin (120 ± 8 µg/g) the major phenolics in HS. Among the 14 micronutrients we identified, zinc and boron were the most abundant metals detected in HS. In line with previous studies involving liver diseases, our data supports evidence that such phenolics and metals present in HS may prevent liver injury induced by acetaminophen.

GRADE guidance 24 optimizing the integration of randomized and non-randomized studies of interventions in evidence syntheses and health guidelines.

BACKGROUND AND OBJECTIVE: This is the 24th in the ongoing series of articles describing the GRADE approach for assessing the certainty of a body of evidence in systematic reviews and health technology assessments and how to move from evidence to recommendations in guidelines. METHODS: Guideline developers and authors of systematic reviews and other evidence syntheses use randomized controlled studies (RCTs) and non-randomized studies of interventions (NRSI) as sources of evidence for questions about health interventions. RCTs with low risk of bias are the most trustworthy source of evidence for estimating relative effects of interventions because of protection against confounding and other biases. However, in several instances, NRSI can still provide valuable information as complementary, sequential, or replacement evidence for RCTs. RESULTS: In this article we offer guidance on the decision regarding when to search for and include either or both types of studies in systematic reviews to inform health recommendations. CONCLUSION: This work aims to help methodologists in review teams, technology assessors, guideline panelists, and anyone conducting evidence syntheses using GRADE.

A novel event-related fMRI supervoxels-based representation and its application to schizophrenia diagnosis.

BACKGROUND AND OBJECTIVE: The schizophrenia diagnosis represents a difficult task because of the confusing descriptions of symptoms given by the patient, their similarity among several disorders, the lower familiarity with genetic predisposition, and the probably inadequate response to the treatment. Neuro-biological markers of schizophrenia, as a quantitative relationship between the psychiatrist's reports and the biology of the brain, could be used. Functional Magnetic Resonance Imaging (fMRI) obtain the subject's performance in cognitive tasks and may find significant differences between the patient's data and controls. The input data of classifiers may imply alterations in diagnosis; therefore, it is essential to ensure an adequate representation to describe the entire dataset classified. METHODS: We propose a supervoxels-based representation calculated by two main steps: the short-range connectivity, supervoxels' generation using a Fuzzy Iterative Clustering algorithm, and the long-range connectivity, employing Detrended Cross-Correlation Analysis among supervoxels. The unrelated supervoxels, through a statistical test based on critical points calculated empirically, are removed. The remainder supervoxels are the input for feature selectors to extract the discriminative supervoxels. We implement support vector machine classifiers using the correlation coefficient of the significant supervoxels. The dataset of 1.5 Tesla was downloaded from the SchizConnect site, where the fMRI data, during an auditory oddball task, was acquired. We calculate the performance of the classifiers using a leave-one-out cross-validation and compute the area under the Receiver Operating Characteristic curve and a permutation test to ensure no bias in the classifiers. RESULTS: According to the permutation test, with p-values less than the significance level of 0.05, the classifiers extract discriminative class structure from data where no bias is shown. Our supervoxels-based representation gets the maximum values of sensitivity, specificity, and accuracy of 92.9%, 100%, and 96.4%, respectively. The discriminative brain regions, to discern among patients and controls, are extracted; these regions also are mentioned by the related works. CONCLUSIONS: The proposed representation, based on supervoxels, is a data-driven model that does not use predefined models of the signal nor pre-relocated brain regions of interest. The results are competitive against the related works, and the relevant supervoxels are related to the schizophrenia diagnosis.

Case report: Polyarteritis nodosa as a substrate for a massive myocardial infarction.

This report describes a rare case of a global myocardial infarction caused by severe vasospasm of the coronary arteries secondary to the administration of pyridostigmine in a patient with polyarteritis nodosa (PAN). Details about the clinical presentation, the typical electrocardiographic pattern of multivessel disease, the differential diagnoses suspected in the multi-imaging approach, and the treatment of cardiogenic shock are described. The definitive diagnosis of infarction and the histopathological findings compatible with polyarteritis nodosa were made by autopsy.

Documento de consenso sobre el uso de los iSGLT2 en el tratamiento de pacientes con diabetes mellitus tipo 2 / Consensus on the use of iSGLT2 in the treatment of patients with type 2 diabetes mellitus

Resumen Aunque en los últimos años en México ha mejorado la calidad de la atención de la diabetes mellitus (DM) y ha aumentado el acceso a servicios de salud y medicamentos, existe una falta de apego a las recomendaciones de las guías de práctica clínica, que podría explicar la falta de un control glucémico adecuado en muchos de los pacientes con DM. Los inhibidores del cotransportador de sodio-glucosa tipo 2 (iSGLT2) han sido la última clase de agentes antidiabéticos en recibir la aprobación de la Food and Drug Administration (FDA) y de la Comisión Federal para la Protección contra Riesgos Sanitarios de México (COFEPRIS). Con el fin de mejorar el uso de los iSGLT2 en la práctica clínica en México, en este documento se presentan las recomendaciones emitidas por un panel de 11 expertos mexicanos con base en las nuevas evidencias publicadas para el tratamiento de los pacientes con DM2.

Abstract Although in recent years in Mexico the quality of diabetes mellitus (DM) care has improved and access to health services and medications has increased, there is a lack of adherence to the recommendations of the clinical guidelines, which could explain the poor glycemic control in many of the patients with DM. Sodium-glucose cotransporter type 2 (iSGLT2) inhibitors have been the last class of antidiabetic agents to receive approval from the Food and Drug Administration (FDA) and COFEPRIS (Mexico). In order to improve the use of SGLT2i in clinical practice in Mexico, this paper presents the recommendations issued by a panel of eleven Mexican experts based on the new published evidence for the treatment of patients with DM2.

Hormone exposure and its suppressive effect on risk of high-grade gliomas among patients with breast cancer.

BACKGROUND: Prior reports demonstrate the expression of estrogen and progesterone receptors in high-grade gliomas (HGGs), but the relationship between hormone receptor-positive disease and risk of HHGs in patients with breast cancer (BC) remains uncharacterized. METHODS: Using the SEER 18 registries (2000-2017), we examined the temporal trend of the incidence of HGGs and BC. The standardized incidence ratio was calculated to assess the risk of subsequent HGG in BC patients. RESULTS: During the study period, the incidence of BC and HGGs remained comparable for men and women. Among 976,134 patients with BC, we found a decreased incidence of HGGs in females, but not in males. Female BC patients with hormone receptor-positive disease were at a lower risk of developing glioblastoma and anaplastic astrocytoma. CONCLUSION: Our study findings allude to the protective role of hormone exposure in the development of HGGs, which may lead to the development of therapies targeting hormonal pathways.