Third National Registry of Cardiac Rehabilitation Programs in Mexico (RENAPREC III-2022) / Tercer Registro Nacional de Programas de Rehabilitación Cardiaca en México (RENAPREC III-2022)

Abstract Introduction: In Mexico, cardiac rehabilitation (CR) as an interdisciplinary intervention with therapeutic impact in patients with heart disease is growing. There is the need to know actual conditions of CR in our country. Objectives: The objective of this National Registry is to follow-up those existing and new CR units in Mexico through the comparison between the two previous registries, RENAPREC-2009 and RENAPREC II-2015 studies. This is a descriptive study focused on diverse CR activities such as assistance training, and certification of health professionals, barriers, reference, population attended, interdisciplinarity, permanence over time, growth prospects, regulations, post-pandemic condition, integrative characteristics, and scientific research. Results: Data were collected from 45 CR centers in the 32 states, 75.5% are private practice units, 67% are new, 33% were part of RENAPREC II-2015, and 17 have continued since 2009. With a better distribution of CR units along the territory, the median reference of candidates for CR programs is 9% with a significant reduction into tiempo of enrollment to Phase II admission (19 ± 11 days). Regarding to previous registries, the coverance of Phases I, II, and III is 71%, 100%, and 93%, respectively; and a coverance increases in evaluation, risk stratification, and prescription, more comprehensive attendance and prevention strategies. Conclusions: CR in Mexico has grown in the past 7 years. Even there is still low reference and heterogeneity in specific processes, there are strengths such as interdisciplinarity, scientific professionalization of specialists, national diversification, and an official society that are consolidated over time.

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A regioselective synthesis of 3,4-diaryl-1H-pyrazoles through a 1,3-dipolar cycloaddition of tosylhydrazones and nitroalkenes.

A procedure for the selective synthesis of 3,4-diaryl-1H-pyrazoles through a 1,3-dipolar cycloaddition is reported. The transformation occurred under mild conditions using affordable tosylhydrazones and nitroalkenes commencing from benzaldehydes/heteroaromatic aldehydes as starting materials. Due to the versatility of this protocol, we prepared a vast collection of 3,4-diaryl-1H-pyrazoles, which included the incorporation of heterocyclic rings at the pyrazole core. Two-dimensional NMR techniques (2D-NOESY and HMBC) confirmed the regioselectivity of the transformation and correlated well with DFT calculations. Accordingly, the analysis of the transition states indicated that the 3,4-diaryl product corresponded to the product with the lowest activation energy and led to the most stable product. Finally, the series was evaluated against three cancer cell lines, with compound 8f being the most remarkable analog in terms of activity and extraordinary selectivity towards PC-3 compared to the other cell lines (including COS-7).

Transcatheter aortic valve replacement in pure native aortic regurgitation: when off-label indications match the patient's requirements / TAVI en IA pura de válvula nativa: cuando indicaciones fuera de guías cumplen los requerimientos del paciente

Abstract Objective: In recent years, transcatheter aortic valve replace (TAVR) has revolutionized the interventional treatment of aortic stenosis, however, only scarce evidence considers it as treatment for Aortic Regurgitation (AR). At present, the treatment of Pure AR of Native Valve with TAVR does not fall within the recommendations of international guidelines, as it poses multiple challenges with immediate and long-term variable and unpredictable results. The objective of this paper is to present the case of a patient with prohibitive operative risk that benefited of TAVR treatment for AR. Materials and methods: We present the case of a 79-year-old male patient who has severe Pure Native Aortic Valve Regurgitation, considered inoperable. Based on the heart team's decision, TAVR was planned with the use of an Edwards SAPIEN 3 valve. After TAVR, the patient developed complete heart block and a pacemaker was implanted. He improved to NYHA II functional class. At 15-month follow-up, he suffered intracranial hemorrhage and passed away. Results and Conclusions: Management of patients with severe symptomatic AR with high surgical risk continues to be a special challenge. They have high mortality if left untreated with valvular change, despite medical treatment. Even though it is strictly off-label, TAVR might be a reasonable solution for a select type of patients who are considered inoperable due to surgical high mortality risk.

Resumen Objetivo: En años recientes, el reemplazo valvular aórtico vía percutánea (TAVI) ha revolucionado el tratamiento de los pacientes con estenosis aórtica, sin embargo, poca evidencia la considera como opción de tratamiento en pacientes con insuficiencia aórtica (IA), especialmente en pacientes con Insuficiencia Aórtica Pura de Válvula Nativa (IAPVN), dado que esta patología confiere múltiples retos con resultados muy variables tanto a corto como a largo plazo. Dada su alta mortalidad en caso de permanecer sin tratamiento, la primera opción de tratamiento es la cirugía de cambio valvular. Material y Métodos: Presentamos el caso de un masculino de 79 años con IAPVN grave considerado inoperable dadas las comorbilidades. De acuerdo con la decisión del equipo de Cardiología, se decidió realizar TAVI con la colocación de una Válvula Edwards SAPIEN 3. El paciente desarrolló bloqueo AV completo como única complicación y se colocó marcapasos permanente. Permaneció en clase funcional NYHA II. A los 15 meses de seguimiento presentó hemorragia intracraneal y falleció. Resultados y Conclusiones: El manejo de los pacientes con IAPVN grave sintomática con riesgo quirúrgico alto sigue siendo un reto especial. Tienen alta mortalidad si no se realiza cambio valvular a pesar de tratamiento médico. A pesar de que no se recomienda en las guías actuales, la TAVI puede ser una opción razonable para un grupo muy selecto de pacientes que son considerados inoperables.

Expanding the structure-activity relationship of cytotoxic diphenyl macrocycles.

Twenty-four biaryl tetrapeptide macrocycles were synthesized as an extension of our previous work. Two groups of compounds were constructed for establishing a structure-activity relationship: one having an aromatic substituent at α-position of one exo-peptide and the other group with a variation in the size of the lipophilic chain. Compound 13t had the best cytotoxicity from all the compounds tested (in a panel of six human cancer cell lines) and low toxicity on one healthy cell line. The study identified the lipophilic chain as the main structural moiety for improving the biological activity, being the seven-carbon chain the optimal length. On the other hand, the aromatic rings at α-position did not enhance the cytotoxicity.

Greenhouse gas emissions from cattle dung depositions in two Urochloa forage fields with contrasting biological nitrification inhibition (BNI) capacity.

Grazing-based production systems are a source of soil greenhouse gas (GHG) emissions triggered by excreta depositions. The adoption of Urochloa forages (formerly known as Brachiaria) with biological nitrification inhibition (BNI) capacity is a promising alternative to reduce nitrous oxide (N2O) emissions from excreta patches. However, how this forage affects methane (CH4) or carbon dioxide (CO2) emissions from excreta patches remains unclear. This study investigated the potential effect of soils under two Urochloa forages with contrasting BNI capacity on GHG emissions from cattle dung deposits. Additionally, the N2O and CH4 emission factors (EF) for cattle dung under tropical conditions were determined. Dung from cattle grazing star grass (without BNI) was deposited on both forage plots: Urochloa hybrid cv. Mulato and Urochloa humidicola cv. Tully, with a respectively low and high BNI capacity. Two trials were conducted for GHG monitoring using the static chamber technique. Soil and dung properties and GHG emissions were monitored in trial 1. In trial 2, water was added to simulate rainfall and evaluate GHG emissions under wetter conditions. Our results showed that beneath dung patches, the forage genotype influenced daily CO2 and cumulative CH4 emissions during the driest conditions. However, no significant effect of the forage genotype was found on mitigating N2O emissions from dung. We attribute the absence of a significant BNI effect on N2O emissions to the limited incorporation of dung-N into the soil and rhizosphere where the BNI effect occurs. The average N2O EFs was 0.14%, close to the IPCC 2019 uncertainty range (0.01-0.13% at 95% confidence level). Moreover, CH4 EFs per unit of volatile solid (VS) averaged 0.31 g CH4 kgVS-1, slightly lower than the 0.6 g CH4 kgVS-1 developed by the IPCC. This implies the need to invest in studies to develop more region-specific Tier 2 EFs, including farm-level studies with animals consuming Urochloa forages to consider the complete implications of forage selection on animal excreta based GHG emissions.

Multicomponent synthesis and anti-proliferative screening of biaryl triazole-containing cyclophanes.

We report a practical two-step approach involving a Ugi 4-CR/ azide-alkyne cycloaddition for the synthesis of biaryl-containing cyclophanes. The series represents an extension of our previously reported macrocycles as an effort to enhance the anti-proliferative activity of this scaffold. In this variant, we incorporate a biphenyl moiety in the framework, thus enhancing the macrocycle size, lipophilicity, and structural diversity. Macrocycles were tested against different cell lines, being more cytotoxic against prostate (PC-3 and DU-145) and breast (MCF-7) tumor cells. Gratifyingly, the most active compound showed a significative enhancement of PC-3 growth inhibition with respect to our previous series, reaffirming the potential anti-proliferative activity of this kind of cyclophanes.

Multicomponent synthesis and preliminary anti-inflammatory activity of lipophilic diphenylamines.

Non-Steroidal Anti-inflammatory Drugs (NSAIDs) are some of the most prescribed medications for pain but the incidence of adverse effects -especially during chronic treatment- points out the requirement of new analgesics. In this study, we showed an efficient two-steps synthesis of diphenylamine-containing dipeptides consisting of a multicomponent process followed by a Buchwald-Hartwig cross-coupling reaction. We prepared 16 diphenylamine derivatives and evaluated their in vivo anti-inflammatory activity through an ear edema model using 12-O-tetradecanoylpholbol-13-acetate. Furthermore, the toxicity of the more potent compounds in the Artemia salina model and their cell viability using murine RAW 264.7 cells is reported. The fluorinated compound 10k becomes a reliable candidate since it reduced the TPA-induced edema to 92%, lacked cytotoxicity against murine macrophages, and had minimal toxicity in Artemia salina.

Diarrheagenic Escherichia coli pathotypes isolated from a swine farm in a region of Morelos state, Mexico / Patotipos diarreicos de Escherichia coli aislados de una granja porcina en una región del estado de Morelos, México

Abstract: Objective: Determine the frequency of diarrheagenic Escherichia coli pathotypes colonizing swine. Materials and methods: E. coli strains isolated of fecal samples from 280 swine, produced for local consumption, in a semi-technical farm of Morelos state (central Mexico), were tested to identify the diarrheagenic E. coli pathotypes by multiplex PCR. Pulsed-field gel electrophoresis (PFGE) were determined for the study of genetic diversity between pathigenic E. coli strains. Results: Of the 521-diarrheagenic E. coli isolates examined, 50 (9.6%) were positive for at least one virulence gene in 42 different animals. Thus, 15% (42/280) of the swine in this farm were colonized with pathogenic E. coli. Among the E. coli isolates, the pathotype EPEC (6.5%) was the most frequently, followed by EHEC (2.3%), ETEC and EIEC (0.4%). The study of genetic diversity, carried out by PFGE of 40 representative isolates, revealed 25 distinct restriction profiles clustered in 21 groups (A-U). Conclusions: In this study, four different E. coli pathotypes were found among swine colonized by E. coli in this farm. Thus, these swine are reservoirs for these virulent bacteria and there is potential risk of causing diarrhea in swine and in the population consuming the meat.

Resumen: Objetivo: Determinar la frecuencia de patotipos diarreicos de Escherichia coli que colonizan cerdos. Material y métodos: Se analizaron cepas de E. coli aisladas de muestras fecales de 280 cerdos, producidas para consumo local, en una granja del estado de Morelos (centro de México) para identificar los patotipos diarreicos de E. coli por PCR multiplex. Se determinó la electroforesis en gel de campo pulsado (PFGE) para el estudio de la diversidad genética entre cepas patógenas de E. coli. Resultados: De los 521 aislados de E. coli con patotipos diarreicos examinados, 50 (9.6%) fueron positivos para al menos un gen de virulencia en 42 animales diferentes. Así, 15% (42/280 porcinos) fueron colonizados con E. coli patógeno. Entre los aislados de E. coli de porcinos, el patotipo EPEC (6.5%) fue el más frecuente, seguido por EHEC (2.3%), ETEC y EIEC (0.4%). El estudio de la diversidad genética, realizado por PFGE de 40 cepas representativas, reveló 25 perfiles de restricción distintos agrupados en 21 grupos (A-U). Conclusiones: En este estudio, se encontraron cuatro diferentes patotipos de E. coli entre los cerdos colonizados por E. coli. Estos cerdos son reservorios de estas bacterias virulentas y existe un riesgo potencial de causar diarrea en los cerdos y en la población que consume la carne.

Effect of High-Dose Topical Minoxidil on Erythrocyte Quality in SKH1 Hairless Mice.

SKH1 hairless mice are widely used in carcinogenesis and dermatology research due to their bare skin, as exposure to different agents is facilitated. Minoxidil is a cosmetic drug that is recognized as a mitogenic agent, and mitogens are suggested to have carcinogenic and mutagenic potential by inducing cell division and increasing the possibility of perpetuating DNA damage. Therefore, we hypothesized that the application of high doses of minoxidil to the skin of hairless mice would increase the number of micronucleated erythrocytes (MNEs) in peripheral blood. The objective of this study was to evaluate the topical administration of high doses of minoxidil on peripheral blood erythrocytes of SKH1 mice by means of micronucleus assay. Minoxidil was administered on the entire body surface of mice every 12 or 24 h. Minoxidil dosing every 24 h increased the number of micronucleated polychromatic erythrocytes (MNPCEs), and dosing every 12 h increased the number of MNEs and MNPCEs, as compared to baseline and the negative control group. No decrease in polychromatic erythrocyte frequencies was observed in the minoxidil groups. Therefore, topical application of high minoxidil doses to mice can produce DNA damage, as observed through an increase in the number of MNEs, without producing cytotoxicity, possibly due to its mitogenic effect.

The Role of Dietary Antioxidants on Oxidative Stress in Diabetic Nephropathy.

Diabetic nephropathy (ND) is the leading cause of end-stage renal disease and oxidative stress (OS) has been recognized as a key factor in the pathogenesis and progression. Hyperglycemia, reactive oxygen species, advanced glycation end products, arterial pressure, insulin resistance, decrease in nitric oxide, inflammatory markers, and cytokines, among others; are involved in the presence of OS on ND. This revision focus on diverse studies in experimental and human models with diabetes and DN that has been demonstrated beneficial effects of different dietary antioxidant as resveratrol, curcumin, selenium, soy, catechins, α-lipoic acid, coenzyme Q10, omega-3 fatty acids, zinc, vitamins E and C, on OS and the capacity for antioxidant response. Therefore, this interventions could have a positive clinical impact on DN.

A Two-Step Multicomponent Synthetic Approach and Anti-inflammatory Evaluation of N-Substituted 2-Oxopyrazines.

Inflammation is widely reported as a main factor for the development of chronic diseases such as cancer, diabetes, and even metabolic syndrome. Thus, the search for novel anti-inflammatory compounds is required. Herein we describe the synthesis of a collection of peptidic pyrazinones by a convenient approach involving a multicomponent isocyanide-based reaction followed by a tandem deprotection/oxidative cyclization step. This series of compounds were tested for their potential anti-inflammatory capacity in an in vivo murine model, and four compounds were identified to inhibit tetradecanoylphorbol acetate (TPA)-induced edema by more than 75 %. The two most active compounds, N-benzyl-2-(4-hydroxy-3,5-dimethoxyphenyl)-2-[2-oxopyrazin-1(2H)-yl]acetamide (10 o) and N-cyclohexyl-2-[2-oxopyrazin-1(2H)-yl]-2-[4-(trifluoromethyl)phenyl]acetamide (10 x), with methyl and trifluoromethyl groups, were also able to decrease myeloperoxidase activity and leukocyte infiltration. Moreover, 10 x decreased the thickness of TPA-treated mouse ears, as observed in histological analysis of the tissues.

Corrección de los múltiplos de la mediana de los biomarcadores del modelo de predicción de preeclampsia de la Fetal Medicine Foundation para población mexicana / Correction of the multiples of median of the biomarkers used in the Fetal Medicine Foundation's prediction model for preeclampsia in Mexican population

Resumen OBJETIVO: Calcular y ajustar los múltiplos de la mediana para el índice de pulsatilidad medio de las arterias uterinas, presión arterial media materna, factor de crecimiento placentario y proteína plasmática A asociada al embarazo, a fin de valorar el desempeño diagnóstico del modelo corregido de preeclampsia de la Fetal Medicine Foundation en población mexicana. MATERIALES Y MÉTODOS: Estudio de casos y controles anidado en una cohorte prospectiva efectuado en el Centro de Salud Dr. Galo Soberón y Parra entre el 1 de octubre de 2015 y el 30 de junio de 2016. Criterio de inclusión: pacientes con embarazo de 11-13.6 semanas. Criterio de exclusión: pacientes de riesgo no seleccionado, con embarazo único, entre 11 y 13.6 semanas calculadas por ecografía mediante longitud cráneo cauda. Criterio de eliminación: pacientes que abandonaron el estudio. Se evaluaron el índice de pulsatilidad medio de las arterias uterinas, la presión arterial media, los valores séricos del factor de crecimiento placentario y la proteína plasmática A asociada al embarazo. Se comparó la diferencia en la distribución de los biomarcadores entre la observada en población mexicana y la esperada según la formula original de la Fetal Medicine Foundation. Cuando la diferencia fue mayor a 0.2 múltiplos de la mediana, se utilizó la mediana del observado como coeficiente de ajuste a la fórmula original del esperado. RESULTADOS: De las 300 pacientes reclutadas, 292 concluyeron el estudio. La media de semanas de embarazo al momento del tamizaje fue de 12.4 (desviación estándar 0.72). La prevalencia de preeclampsia fue de 4.5% (13 de 292). Se encontraron diferencias importantes en la distribución de múltiplos de la mediana para el índice de pulsatilidad medio de las arterias uterinas, factor de crecimiento placentario y proteína plasmática A asociada al embarazo. Posterior a la corrección de los biomarcadores, la sensibilidad, falsos positivos y área bajo la curva del modelo ajustado para detectar cualquier preeclampsia fue de 92% (12 de 13), 5.7% (16 de 279) y 93.3%, respectivamente. CONCLUSIONES: La distribución de los múltiplos de la mediana en población mexicana es distinta para los biomarcadores: factor de crecimiento placentario, proteína plasmática A asociada al embarazo e índice de pulsatilidad medio de las arterias uterinas. El ajuste de estos biomarcadores para población mexicana resulta en un buen desempeño diagnóstico del modelo de preeclampsia.

Abstract OBJECTIVE: Calculate and adjust the multiples of the median (MoMs) for the mean pulsatility index of uterine arteries (IPm Aut), mean arterial pressure (PAM), placental growth factor (PlGF) and plasma protein associated with pregnancy (PAPP-A), in order to assess the diagnostic performance of the corrected preeclampsia model of the fetal medicine foundation in the Mexican population. MATERIALS AND METHODS: Case-control study nested in a prospective cohort conducted at the "Dr. Galo Soberón y Parra "from October 1, 2015 - June 30, 2016. Patients with pregnancy of 11-13.6 weeks were included, multiple pregnancies or older than 14 weeks were excluded and patients with medication intake prior to pregnancy; Patients who decided to leave the study were eliminated. Autm IPm, PAM, PlGF and PAPP-A serum values were evaluated. The difference in the distribution of biomarkers between that observed in the Mexican population and that expected was compared according to the original formula of the Fetal Medicine Foundation. When the difference was greater than 0.2 MoMs, the median observed was used as an adjustment coefficient to the original expected formula. RESULTS: Of the 300 patients recruited, 292 concluded the study. The average gestational age at the time of screening was 12.4 weeks (standard deviation [SD] 0.72). The prevalence of preeclampsia was 4.5% (13/292). Important differences were found in the distribution of multiples of the median (MoMs) for IPm Aut, PlGF and PAPP-A. After correction of the biomarkers, the sensitivity, false positives and area under the curve (AUC) of the model adjusted to detect any preeclampsia was 92% (12/13), 5.7% (16/279) and 93.3%, respectively . CONCLUSIONS: The distribution of MoMs in the Mexican population is different for the PlGF, PAPP-A and IPm Aut biomarkers. The adjustment of these biomarkers to the Mexican population results in a good diagnostic performance of the preeclampsia model.

Oral acyclovir induced hypokalemia and acute tubular necrosis a case report.

BACKGROUND: Acyclovir is one of the most common prescribed antiviral drugs. Acyclovir nephrotoxicity occurs in approximately 12-48% of cases. It can present in clinical practice as acute kidney injury (AKI), crystal-induced nephropathy, acute tubulointerstitial nephritis, and rarely, as tubular dysfunction. Electrolytes abnormalities like hypokalemia, were previously described only when given intravenously. CASE PRESENTATION: A 54 year-old female presented with weakness and lower extremities paresis, nausea and vomiting after receiving oral acyclovir. Physical examination disclosed a decrease in the patellar osteotendinous reflexes (++ / ++++). Laboratory data showed a serum creatinine level of 2.1 mg/dL; serum potassium 2.1 mmol/L. Kidney biopsy was obtained; histological findings were consistent with acute tubular necrosis and acute tubulointerstitial nephritis. The patient was advised to stop the medications and to start with oral and intravenous potassium supplement, symptoms improved and continued until serum potassium levels were > 3.5 meq/L. CONCLUSIONS: The case reported in this vignette is unique since it is the first one to describe hypokalemia associated to acute tubular necrosis induced by oral acyclovir.

Cytotoxic Activity and Structure-Activity Relationship of Triazole-Containing Bis(Aryl Ether) Macrocycles.

Cancer continues to be a worldwide health problem. Certain macrocyclic molecules have become attractive therapeutic alternatives for this disease because of their efficacy and, frequently, their novel mechanisms of action. Herein, we report the synthesis of a series of 20-, 21-, and 22-membered macrocycles containing triazole and bis(aryl ether) moieties. The compounds were prepared by a multicomponent approach from readily available commercial substrates. Notably, some of the compounds displayed interesting cytotoxicity against cancer (PC-3) and breast (MCF-7) cell lines, especially those bearing an aliphatic or a trifluoromethyl substituent on the N-phenyl moiety (IC50 <13 µm). Additionally, some of the compounds were able to induce apoptosis relative to the solvent control; in particular, (Z)-N-cyclohexyl-7-oxo-6-[4-(trifluoromethyl)phenyl]-11 H-3,10-dioxa-6-aza-1(4,1)-triazola-4(1,3),9(1,4)-dibenzenacyclotridecaphane-5-carboxamide (12 f) was the most potent in this regard (22.7 % of apoptosis).

Inferior vena cava filters in pulmonary embolism: A historic controversy / Filtros de vena cava inferior en tromboembolia pulmonar: Una controversia histórica

Abstract: Objective: Rationale for non-routine use of inferior venous cava filters (IVCF) in pulmonary embolism (PE) patients. Methods: Thrombosis mechanisms involved with IVCF placement and removal, the blood-contacting medical device inducing clotting, and the inorganic polyphosphate in the contact activation pathway were analyzed. In addition, we analyzed clinical evidence from randomized trials, including patients with and without cancer. Furthermore, we estimated the absolute risk reduction (ARR), the relative risk reduction (RRR), and the number needed to treat (NNT) based on the results of each study using a frequency table. Finally, we analyzed the outcome of our PE patients that were submitted to thrombolysis with short and long term follow-up. Results: IVCF induces thrombosis by several mechanisms including placement and removal, rapid protein adsorption, and simultaneous surface-induced activation via the contact activation pathway. Also, inorganic polyphosphate has an important role as a procoagulant, reversing the effect of anticoagulants. Randomized control trials included 904 cancer and non-cancer PE patients. In terms of ARR, RRR, and NNT, there is no evidence for routine use of IVCF. In 290 patients with proved PE, extensive thrombotic burden and right ventricular dysfunction under thrombolysis and oral anticoagulation, we observed a favorable outcome in a short- and long-term follow-up; additionally, IVCF was only used in 5% of these patients. Conclusion: Considering the complex mechanisms of thrombosis related with IVCF, the evidence from randomized control trials and ARR, RRR, and NNT obtained from venous thromboembolism patients with and without cancer, non-routine use of IVCF is recommended.

Resumen: Objetivo: Racionalidad para no utilizar en forma rutinaria filtros de vena cava inferior (FVCI) en pacientes con tromboembolia pulmonar (TEP). Métodos: Analizamos mecanismos de trombosis relacionados con la colocación o retiro de estos dispositivos médicos, incluyendo la importancia del polifosfato inorgánico en la vía de activación de contacto. Analizamos evidencia clínica de estudios aleatorizados controlados en pacientes con y sin cáncer. Mediante tablas de frecuencia estimamos de cada estudio reducción del riesgo absoluto (RRA) y relativo (RRR) y el número necesario a tratar (NNT). Finalmente, examinamos la evolución de nuestros pacientes con TEP llevados a trombolisis con seguimientos a corto y largo plazo. Resultados: FVCI inducen trombosis por diferentes mecanismos: colocación y retiro, adsorción rápida de proteínas y activación de superficie inducida en la vía de activación de contacto. El polifosfato inorgánico es un procoagulante importante para la anticoagulación. Estudios aleatorizados controlados incluyeron 904 pacientes con TEP con y sin cáncer. En términos de RRA, RRR y NNT no existe evidencia para el uso rutinario. En 290 pacientes con TEP probada, importante carga de trombo y disfunción del ventrículo derecho llevados a trombolisis y anticoagulación observamos una evolución favorable en seguimientos a corto y largo plazo. En estos pacientes los FVCI se utilizaron solo en el 5%. Conclusión: Considerando los mecanismos complejos de trombosis relacionados con los FVCI, la evidencia obtenida de los estudios aleatorizados y controlados, así como la RRA, RRR y NNT en pacientes con tromboembolismo venoso con y sin cáncer, no recomendamos el uso rutinario de FVCI.

Two cases of atypical hemolytic uremic syndrome (aHUS) and eosinophilic granulomatosis with polyangiitis (EGPA): a possible relationship.

Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by hemolysis, thrombocytopenia, and renal failure. It is related to genetic mutations of the alternative complement pathway and is difficult to differentiate from other prothrombotic microangiopathies. Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss syndrome, CSS) is a systemic ANCA-associated vasculitis and a hypereosinophilic disorder where eosinophils seem to induce cell apoptosis and necrosis and therefore, vasculitis. Here, we report the case of two CSS patients with a genetic complement disorder consistent with aHUS diagnosis. Both patients showed histologic features that supported the diagnosis of CSS, and a genetic complement study confirmed the suspected aHUS diagnosis. In the case where eculizumab was administered, the global response was excellent. There is very limited understanding of the genetics and epidemiology of both, atypical HUS and EGPA, but considering our two patients we suggest that an etiopathogenic link exists among patients diagnosed with both entities.

Autopercepción de la salud, presencia de comorbilidades y depresión en adultos mayores mexicanos: propuesta y validación de un marco conceptual simple / Self-rated health, multimorbidity and depression in Mexican older adults: Proposal and evaluation of a simple conceptual model

Resumen Introducción. La autopercepción de la salud es una concepción individual y subjetiva que resulta de la intersección entre factores biológicos, sociales y psicológicos, y proporciona una evaluación única e inestimable del estado general de salud de una persona. Objetivo. Proponer y evaluar un modelo conceptual simple para entender la autopercepción de la salud y su relación con la presencia de comorbilidades, discapacidad y síntomas depresivos en adultos mayores mexicanos. Materiales y métodos. Se hizo un estudio transversal basado en una muestra representativa nacional de 8.874 adultos de 60 y más años. Se determinó la autopercepción positiva de la salud mediante una escala de tipo Likert con la pregunta: "¿Cómo considera que es su estado actual de salud?", así como de las variables intermedias de presencia de comorbilidades, discapacidad y síntomas depresivos, y variables exógenas dicotómicas (sexo, tener pareja, percepción de la participación en las decisiones del hogar y pobreza). Para validar el modelo conceptual propuesto, se diseñó un modelo generalizado de ecuaciones estructurales con función de enlace logit para la autopercepción positiva de la salud. Resultados. Se encontró una asociación de vías directas entre la presencia de comorbilidades y la autopercepción positiva de la salud (odds ratio, OR=0,48; IC95% 0,42-0,55), entre la discapacidad y la autopercepción positiva de la salud (OR=0,35; IC95% 0,30-0,40), y entre los síntomas depresivos y la autopercepción positiva de la salud (OR=0,38; IC95% 0,34-0,43). El modelo también validó asociaciones indirectas entre discapacidad y síntomas depresivos (OR=2,25; IC95% 2,01-2,52), presencia de comorbilidades y síntomas depresivos (OR=1,79; IC95% 1,61-2,00), y presencia de comorbilidades y discapacidad (OR=1,98; IC95% 1,78-2,20). Conclusiones. Se hizo la evaluación empírica de un modelo teórico parsimonioso, lo cual permitió determinar asociaciones directas e indirectas con la autopercepción positiva de la salud.

Abstract Introduction: Self-rated health is an individual and subjective conceptualization involving the intersection of biological, social and psychological factors. It provides an invaluable and unique evaluation of a person's general health status. Objective: To propose and evaluate a simple conceptual model to understand self-rated health and its relationship to multimorbidity, disability and depressive symptoms in Mexican older adults. Materials and methods: We conducted a cross-sectional study based on a national representative sample of 8,874 adults of 60 years of age and older. Self-perception of a positive health status was determined according to a Likert-type scale based on the question: "What do you think is your current health status?" Intermediate variables included multimorbidity, disability and depressive symptoms, as well as dichotomous exogenous variables (sex, having a partner, participation in decision-making and poverty). The proposed conceptual model was validated using a general structural equation model with a logit link function for positive self-rated health. Results: A direct association was found between multimorbidity and positive self-rated health (OR=0.48; 95% CI: 0.42-0.55), disability and positive self-rated health (OR=0.35; 95% CI: 0.30-0.40), depressive symptoms and positive self-rated health (OR=0.38; 95% CI: 0.34-0.43). The model also validated indirect associations between disability and depressive symptoms (OR=2.25; 95% CI: 2.01-2.52), multimorbidity and depressive symptoms (OR=1.79; 95% CI: 1.61-2.00) and multimorbidity and disability (OR=1.98; 95% CI: 1.78-2.20). Conclusions: A parsimonious theoretical model was empirically evaluated, which enabled identifying direct and indirect associations with positive self-rated health.

Diversity-oriented synthesis and cytotoxic activity evaluation of biaryl-containing macrocycles.

Synthesis of biaryl-containing macrocycles has been carried out through a four-step approach comprising two Ugi four component reactions and a Suzuki-Miyaura macrocyclization. This protocol allowed the synthesis of 12- and 14-membered macrocycles. Cytotoxic activity evaluation showed that some of the molecules were effective against leukemia, glioblastoma and lung cancer cell lines (IC50 = 4.0, 5.9 and 7.6, respectively).

Inferior vena cava filters in pulmonary embolism: A historic controversy.

OBJECTIVE: Rationale for non-routine use of inferior venous cava filters (IVCF) in pulmonary embolism (PE) patients. METHODS: Thrombosis mechanisms involved with IVCF placement and removal, the blood-contacting medical device inducing clotting, and the inorganic polyphosphate in the contact activation pathway were analyzed. In addition, we analyzed clinical evidence from randomized trials, including patients with and without cancer. Furthermore, we estimated the absolute risk reduction (ARR), the relative risk reduction (RRR), and the number needed to treat (NNT) based on the results of each study using a frequency table. Finally, we analyzed the outcome of our PE patients that were submitted to thrombolysis with short and long term follow-up. RESULTS: IVCF induces thrombosis by several mechanisms including placement and removal, rapid protein adsorption, and simultaneous surface-induced activation via the contact activation pathway. Also, inorganic polyphosphate has an important role as a procoagulant, reversing the effect of anticoagulants. Randomized control trials included 904 cancer and non-cancer PE patients. In terms of ARR, RRR, and NNT, there is no evidence for routine use of IVCF. In 290 patients with proved PE, extensive thrombotic burden and right ventricular dysfunction under thrombolysis and oral anticoagulation, we observed a favorable outcome in a short- and long-term follow-up; additionally, IVCF was only used in 5% of these patients. CONCLUSION: Considering the complex mechanisms of thrombosis related with IVCF, the evidence from randomized control trials and ARR, RRR, and NNT obtained from venous thromboembolism patients with and without cancer, non-routine use of IVCF is recommended.