Heart transplantation in Mexico. 2006-2019 productivity analysis and Pan American and Iberian comparison.

INTRODUCTION: In Mexico, heart transplants (HTs) have been performed since 1988. OBJECTIVE: To review Mexican productivity in terms of HT between 2006 and 2019 and compare it with that of American and Iberian Peninsula countries. METHODS: Mexican information was collected from HT waiting lists (WL) and from the HTs carried out annually in the period, and was expressed as rates per million population (pmp); 2019 information was compared with that reported at the Pan American and Iberian levels. RESULTS: In the studied period, the rate of HTs in Mexico went from 0.12 pmp in 2006 to 0.25 pmp in 2019, with HTs accounting for between 1 and 2% of all solid organ transplants. Among 13 countries, in 2019 Mexico ranked 12th in the HT rate pmp and 11th in the rate of patients registered for the first time in the WL for a heart (0.42 pmp). Between 2016 and 2019, only one authorized Mexican center reached a volume higher than 10 HT/year. CONCLUSIONS: Given the low figures in the main indicators related to HT in Mexico, it is urgent to rethink health policies in heart failure and HT.

INTRODUCCIÓN: En México se realizan trasplantes de corazón (TC) desde 1988. OBJETIVO: Revisar la productividad mexicana en TC entre 2006 y 2019 y compararla con la de otros países americanos y de la península ibérica. MÉTODOS: Se recabó la información mexicana de las listas de espera (LE) de TC y de los TC realizados anualmente en el periodo, que se expresaron como tasas por millón de pobladores (pmp); la información de 2019 se comparó con la reportada en América y la península ibérica. RESULTADOS: En el periodo estudiado, los TC en México pasaron de 0.12 pmp en 2006 a 0.25 pmp en 2019 y representaron entre 1 y 2 % de todos los trasplantes de órganos sólidos. Entre 13 países, en 2019 México ocupó el 12° lugar en cuanto a la tasa de TC pmp y el 11° lugar en cuanto a la tasa del número de pacientes registrados por primera vez en la LE para un corazón (0.42 pmp). Entre 2016 y 2019, solo un centro mexicano autorizado alcanzó un volumen superior a 10 TC/año. CONCLUSIONES: Debido a las bajas cifras en los principales indicadores relacionados con el TC, en México urge replantear las políticas de salud en insuficiencia cardiaca y TC.

Trasplante de corazón en México. Análisis de la productividad 2006-2019 y comparativa panamericana e ibérica / Heart transplantation in Mexico. 2006-2019 productivity analysis and Pan American and Iberian comparison

Resumen Introducción: En México se realizan trasplantes de corazón (TC) desde 1988. Objetivo: Revisar la productividad mexicana en TC entre 2006 y 2019 y compararla con la de otros países americanos y de la península ibérica. Métodos: Se recabó la información mexicana de las listas de espera (LE) de TC y de los TC realizados anualmente en el periodo, que se expresaron como tasas por millón de pobladores (pmp); la información de 2019 se comparó con la reportada en América y la península ibérica. Resultados: En el periodo estudiado, los TC en México pasaron de 0.12 pmp en 2006 a 0.25 pmp en 2019 y representaron entre 1 y 2 % de todos los trasplantes de órganos sólidos. Entre 13 países, en 2019 México ocupó el 12° lugar en cuanto a la tasa de TC pmp y el 11° lugar en cuanto a la tasa del número de pacientes registrados por primera vez en la LE para un corazón (0.42 pmp). Entre 2016 y 2019, solo un centro mexicano autorizado alcanzó un volumen superior a 10 TC/año. Conclusiones: Debido a las bajas cifras en los principales indicadores relacionados con el TC, en México urge replantear las políticas de salud en insuficiencia cardiaca y TC.

Abstract Introduction: In Mexico, heart transplants (HTs) have been performed since 1988. Objective: To review Mexican productivity in terms of HT between 2006 and 2019 and compare it with that of American and Iberian Peninsula countries. Methods: Mexican information was collected from HT waiting lists (WL) and from the HTs carried out annually in the period, and was expressed as rates per million population (pmp); 2019 information was compared with that reported at the Pan American and Iberian levels. Results: In the studied period, the rate of HTs in Mexico went from 0.12 pmp in 2006 to 0.25 pmp in 2019, with HTs accounting for between 1 and 2% of all solid organ transplants. Among 13 countries, in 2019 Mexico ranked 12th in the HT rate pmp and 11th in the rate of patients registered for the first time in the WL for a heart (0.42 pmp). Between 2016 and 2019, only one authorized Mexican center reached a volume higher than 10 HT/year. Conclusions: Given the low figures in the main indicators related to HT in Mexico, it is urgent to rethink health policies in heart failure and HT.

Protein Misfolding and Aggregation: The Relatedness between Parkinson's Disease and Hepatic Endoplasmic Reticulum Storage Disorders.

Dysfunction of cellular homeostasis can lead to misfolding of proteins thus acquiring conformations prone to polymerization into pathological aggregates. This process is associated with several disorders, including neurodegenerative diseases, such as Parkinson's disease (PD), and endoplasmic reticulum storage disorders (ERSDs), like alpha-1-antitrypsin deficiency (AATD) and hereditary hypofibrinogenemia with hepatic storage (HHHS). Given the shared pathophysiological mechanisms involved in such conditions, it is necessary to deepen our understanding of the basic principles of misfolding and aggregation akin to these diseases which, although heterogeneous in symptomatology, present similarities that could lead to potential mutual treatments. Here, we review: (i) the pathological bases leading to misfolding and aggregation of proteins involved in PD, AATD, and HHHS: alpha-synuclein, alpha-1-antitrypsin, and fibrinogen, respectively, (ii) the evidence linking each protein aggregation to the stress mechanisms occurring in the endoplasmic reticulum (ER) of each pathology, (iii) a comparison of the mechanisms related to dysfunction of proteostasis and regulation of homeostasis between the diseases (such as the unfolded protein response and/or autophagy), (iv) and clinical perspectives regarding possible common treatments focused on improving the defensive responses to protein aggregation for diseases as different as PD, and ERSDs.

Kidney transplant. Pan-American and Iberian productivity analysis in 2019 with a Mexican and chronic kidney disease perspective.

BACKGROUND: Kidney transplant (KT) is the most common solid organ transplantation in the world. OBJECTIVE: To analyze the information from Mexico on KT, waiting lists (WL) and patients on dialysis between 2012 and 2019 and compare that of 2019 with those of the countries of the American Continent, Spain and Portugal. MATERIAL AND METHODS: The required information was obtained from the Global Observatory on Organ Donation and Transplantation (GODT). RESULTS: Between 2012 and 2019, the annual number of kidney transplants (KTs) in Mexico increased by 12.5%, while the WL by December 31 of each year did it by 86.1%. In 2019, Spain and the US reported the highest KT rates, while Mexico ranked 8th in the Pan-American and Iberian comparison, 6th in the American Continent and 4th in Latin America. Mexico did not report to GODT the number of patients on dialysis in 2019 and 2018. CONCLUSIONS: KTs should be considered an integral part of renal replacement therapies. The GODT reports include the numbers of patients on dialysis for each country. Mexico does not always report this data, probably due to the lack of a national registry of chronic kidney disease, the creation of which should be supported.

ANTECEDENTES: El trasplante renal (TR) es el trasplante de órgano sólido más frecuente en el mundo. OBJETIVO: Analizar la información de México sobre TR, listas de espera (LE) y pacientes en diálisis entre 2012-2019 y comparar la del año 2019 con la de los países del continente americano, España y Portugal. MATERIAL Y MÉTODOS: La información requerida se obtuvo del Global Observatory on Organ Donation and Transplantation (GODT). RESULTADOS: Entre 2012-2019 en México el número anual de trasplantes renales (TR) se incrementó en un 12.5%, mientras que la LE al 31 de diciembre de cada año lo hizo en un 86.1%. En 2019, España y EE.UU. reportaron las tasas más altas de TR, mientras que México ocupó el 8.° lugar en la comparativa panamericana e ibérica, 6.° en el Continente Americano y 4.° en América Latina. México no reportó al GODT el número de pacientes en diálisis en 2019 y 2018. CONCLUSIONES: Los TR deben considerarse parte integral de las terapias de reemplazo renal. Los reportes del GODT incluyen las cifras de pacientes en diálisis de cada país. México no siempre reporta este dato, probablemente por carecer de un registro nacional de enfermedad renal crónica, cuya creación debe apoyarse.

Deceased donation and organ transplantation in Mexico. Analysis of 12 years and seven strategic proposals.

BACKGROUND: The evolution of the activity of deceased organ donation and solid organ transplantation in Mexico was analyzed for the period of 2004-2018. METHOD: The information of deceased donation and organ transplantation in Mexico was collected and ordered for said period. When there was no complete information for 2018, the data for 2017 were used instead. Main sources of information: The global observatory on donation and transplantation and the National Transplant Center, Centro National de Trasplantes or CENATRA of the Mexican Secretariat of Health (SSA). RESULTS: (1) In Mexico, deceased donation rates were: 3.2 donations per million population (pmp) in 2007 and 3.94 in 2017, an increase of 23.1%. The rate in 2017 is quite lower than the average reported for Latin America 9.5 donations pmp. (2) The number of patients awaiting a solid organ transplant increased from 4993 in 2007 to 15,448 in 2018, an increase of 309%. (3) In 2017, Mexico reported having 255 authorized centers for renal transplantation, more than any other country in the world. In the case of other -organs: liver, heart, lung, and pancreas, Mexico is the country with the highest number of authorized centers in Latin America. CONCLUSION: The evolution of the figures regarding the activity of deceased donation and solid organ transplantation during the aforementioned study period explains an increasing shortage of organs for transplants in Mexico, despite an apparent large installed capacity. The national organ donation and transplantation system is ineffective and inefficient.

ANTECEDENTES: Se analiza la evolución de la actividad de donación cadavérica de órganos y de la realización de trasplantes de órganos sólidos en México de 2007 a 2018. MÉTODO: Se recolectó y ordenó la información de donación cadavérica y de trasplante de órganos en México en ese período. Cuando no hubo información completa de 2018, se consideró la de 2017. Las principales fuentes de información fueron The Global Observatory on Donation and Transplantation y el Centro Nacional de Trasplantes de la Secretaría de Salud de México. RESULTADOS: 1) La tasa de donación cadavérica de México en 2007 fue de 3.2 donaciones por millón de población (pmp), y en 2017 fue de 3.94 pmp (incremento del 23.1%). La tasa de 2017 está muy por debajo de la media reportada para América Latina (9.5 pmp). 2) El número de pacientes en espera de trasplante de un órgano sólido pasó de 4,993 en 2007 a 15,448 en 2018 (incremento del 309%). 3) En 2017, México reportó tener 255 centros autorizados para trasplante renal, más que cualquier país en el mundo. Para el caso de otros órganos, como hígado, corazón, pulmón y páncreas, México es el país que tiene más centros autorizados en América Latina. CONCLUSIÓN: La evolución de las cifras de donación cadavérica y de trasplante de órganos sólidos en el período de estudio explica una escasez cada vez mayor de órganos para trasplante en México, a pesar de una aparente gran capacidad instalada. El sistema nacional de donación y trasplante de órganos es ineficaz e ineficiente.

Effect of autologous transplant of peripheral blood mononuclear cells in combination with proangiogenic factors during experimental revascularization of lower limb ischemia.

Peripheral blood mononuclear cells (PBMCs) contain a cell fraction of mononuclear progenitor cells (MPCs), which own significant angiogenic potential. Autologous transplant of PBMC and/or platelet-rich plasma (PRP) promotes endothelial cells differentiation in experimental lower limb ischemia, which is considered a safe and effective strategy to support revascularization, either in animal models or clinical trials. In addition, thrombin has been proposed to enrich biological scaffolds, hence increasing MPC viability after intramuscular administration, whereas proangiogenic mediators such as vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF-α), inhibitor of the plasminogen activator-1 (PAI-1), and chemokine (CXCL1; GRO-α) participate in the endothelial response to ischemia, through their proangiogenic effects over endothelial cells proliferation, survival, migration, endothelial integrity maintenance, and physiologic vascular response to injury. In the present study, we describe the effect of autologous PBMCs transplant and PRP, either with or without thrombin, over proangiogenic mediators (measured by enzyme-linked immunosorbent assay) and revascularization response (angiographic vascular pattern at 30 days after vascular occlusion) in a rat model of lower limb ischemia. The group treated with PBMC + PRP significantly induced PAI-1, an effect that was prevented by the addition of thrombin. Furthermore, treatment with PBMC + PRP + thrombin resulted in the induction of VEGF. GRO-α showed a sensitive induction of all proangiogenic mediators. All treatments significantly stimulated revascularization, according to angiographic assessment, whereas higher effect was observed with PBMC + PRP treatment (p < .0001). In conclusion, autologous PBMC transplant stimulates revascularization during experimental ischemia of the lower limb, whereas particular effects over proangiogenic and fibrinolytic mediators may be attributed to PBMCs and its combination with PRP and thrombin.

Cilostazol as a noninferiority pharmacologic option to paclitaxel in early intimal hyperplasia inhibition after venous balloon angioplasty in a rabbit model: a preliminary study.

The development of venous intimal hyperplasia (VIH) has not been fully studied. At present, there are no drugs approved for VIH inhibition; to investigate such alternatives, we aimed to compare paclitaxel with cilostazol in VIH early inhibition in a preliminary experimental model of balloon angioplasty. Twenty-eight male New Zealand rabbits were randomly divided into two groups: cilostazol (A) and paclitaxel (B), which underwent femoral vein barotrauma by a 4 mm balloon angioplasty. The VIH model was previously tested in controls obtaining an 80% increase of subintimal area (SIA) compared with veins without injury (from 0.12 mm2 [standard deviation (SD), 0.05] to 0.86 mm2 [SD, 0.08]). Group A received 20 mg/kg twice daily; group B angioplasty was performed with a single-dose paclitaxel-coated balloon. Seven days later rabbits were euthanized, and vein tissue samples were taken for histological analysis. The primary end point was SIA measure expressed in mm2, and the anticipated difference between treatments was 0.21 mm2. Other measurements were immunohistochemistry expression of hypoxia inducible factor-1 alpha, platelet derived growth factor, and smooth muscle actin, as surrogates of cell migration and oxidative stress. SIA of group A was 0.33 mm2 (SD, 0.15; 95% CI, 0.24-0.42 mm2), and that of group B was 0.31 mm2 (SD, 0.14; 95% CI, 0.22-0.40 mm2). Both drugs showed a reduction of 61% and 63%, respectively, in SIA, compared with controls. The difference between both drugs was 0.0193 mm2 (95% CI, -0.1175 to 0.156 mm2); the statistical difference was found in hypoxia inducible factor-1 alpha expression between both groups. CLINICAL RELEVANCE: Although veins have a thinner middle layer compared with arteries, smooth muscle cells appear to play an important role in venous stenosis after angioplasty. The study of smooth muscle cell response after barotrauma may have clinical applications in the endovascular treatment of venous stenosis, because at the moment, there is no medication indicated to prolong patency after venous endovascular procedures, for example in May Thurner syndrome. Paclitaxel and cilostazol seem to have a promising role. Finally, the present study could inspire a research line to reduce stent placement and increase patency after venous angioplasty.

Alpha-Synuclein Physiology and Pathology: A Perspective on Cellular Structures and Organelles.

Alpha-synuclein (α-syn) is localized in cellular organelles of most neurons, but many of its physiological functions are only partially understood. α-syn accumulation is associated with Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy as well as other synucleinopathies; however, the exact pathomechanisms that underlie these neurodegenerative diseases remain elusive. In this review, we describe what is known about α-syn function and pathophysiological changes in different cellular structures and organelles, including what is known about its behavior as a prion-like protein. We summarize current knowledge of α-syn and its pathological forms, covering its effect on each organelle, including aggregation and toxicity in different model systems, with special interest on the mitochondria due to its relevance during the apoptotic process of dopaminergic neurons. Moreover, we explore the effect that α-syn exerts by interacting with chromatin remodeling proteins that add or remove histone marks, up-regulate its own expression, and resume the impairment that α-syn induces in vesicular traffic by interacting with the endoplasmic reticulum. We then recapitulate the events that lead to Golgi apparatus fragmentation, caused by the presence of α-syn. Finally, we report the recent findings about the accumulation of α-syn, indirectly produced by the endolysosomal system. In conclusion, many important steps into the understanding of α-syn have been made using in vivo and in vitro models; however, the time is right to start integrating observational studies with mechanistic models of α-syn interactions, in order to look at a more complete picture of the pathophysiological processes underlying α-synucleinopathies.

Updates in Mirizzi syndrome.

Mirizzi syndrome, known as extrinsic bile compression syndrome, is a rare complication of cholecystitis and chronic cholelithiasis, secondary to the obliteration of the infundibulum of the gallbladder or cystic duct caused by the impact of one or more calculations in these anatomical structures, which leads to compression of the adjacent bile duct, resulting in partial or complete obstruction of the common hepatic duct, triggering liver dysfunction. Our aim is to identify and describe the current epidemiology, diagnostic methods, and treatment of Mirizzi syndrome. A literature search was performed using different databases, including Medline, Cochrane, Embase, Medscape, PubMed, using keywords: Mirizzi syndrome, epidemiology, markers, pathophysiology, clinical presentation, diagnosis, and treatment. Selected original articles, review articles or case reports from 1997 to 2015 were collected, written in English or Spanish. The endoscopic retrograde cholangiopancreatography (ERCP) is the most accurate diagnostic method. The traditional treatment has been surgery and involves an incision at the bottom of the gallbladder and calculus removal. If fistulas are observed, it is performed a partial cholecystectomy; otherwise, a cholecystocholedochoduodenostomy is an alternative. Endoscopic treatment includes biliary drainage and stone extraction. Many surgeons claim that laparoscopic cholecystectomy is contraindicated in Mirizzi syndrome because of the presence of inflammatory tissue and adhesions in the Calot's triangle. If dissection is attempt, it can cause unnecessary injury to the bile duct. However, other surgeons consider the laparoscopic approach is feasible, although technically challenging. Currently, laparoscopic cholecystectomy for this condition is considered controversial and technically challenging; however, it has shown that with the right skills and equipment, it is a safe and feasible way to treat some cases of Mirizzi syndrome type I and II.

[Increased vascular density with indirect myocardial revascularization in normal rat hearts]. / Mayor densidad vascular con revascularización miocárdica indirecta en corazones normales de ratas

BACKGROUND: The aim of this study was to identify if the interaction of myocardial revascularization methods increases the functional vascular area. METHODS: A 4x3 factorial design was performed in 11 groups, five rats per group, ten samples per rat, evaluated at 45 days postoperative, with different surgical combinations. The magnitude of the interaction was evaluated by immunoexpression of vascular endothelium-derived growth factor, fibroblast growth factor and tyrosine receptor, to allow the activity of vascular endothelium-derived growth factor, fibroblast growth factor and thrombin (Flk-1), as well as vascular area measurement; Both measures were performed by computerized morphometry. RESULTS: An increase in immunohistochemical expression and vascular area in direct proportion to the interaction was identified; It can be affirmed (ANOVA p < 0.0001), that with the interaction of all the maneuvers the maximum effect is achieved. CONCLUSIONS: It is demonstrated that indirect myocardial revascularization has a specific weight within the integral myocardial revascularization with a real impact on cost-benefit and cost-effectiveness.

Introducción: el objetivo de este trabajo fue identificar si la interacción de los métodos de revascularización miocárdica incrementa el área vascular funcional. Métodos: se realizó un estudio con un diseño factorial de 4x3 en 11 grupos, de cinco ratas por grupo, diez muestras por rata, evaluado a 45 días del posoperatorio, con las diferentes combinaciones quirúrgicas. La magnitud de la interacción fue evaluada tanto por inmunoexpresión del factor vascular de crecimiento derivado del endotelio, factor de crecimiento de fibroblastos y receptor de tirosina, para permitir la actividad del factor vascular de crecimiento derivado del endotelio, factor de crecimiento de fibroblastos y trombina (Flk-1), así como de la medición del área vascular; ambas medidas fueron realizadas por morfometría computarizada. Resultados: se identificó un incremento de la expresión inmunohistoquímica y del área vascular en proporción directa con la interacción; se puede afirmar (ANOVA p < 0.0001), que con la interacción de todas las maniobras se logra el efecto máximo. Conclusiones: se demuestra que la revascularización miocárdica indirecta tiene un peso especifico dentro de la revascularización miocárdica integral con un impacto real en el costo-beneficio y el costo-efectividad.

Ascending necrotizing mediastinitis secondary to emphysematous pyelonephritis.

Mediastinal infections usually originate from postoperative complications or in a descending manner from a cervical infectious process; few reports have emerged describing an ascending trajectory. A 56-year-old woman with a Huang class 1 left emphysematous pyelonephritis was referred due to a progression of an ascending necrotizing mediastinitis. A left posterolateral thoracotomy was performed, drainage and thorough lavage were carried out with a successful outcome. We believe this is the first reported case of ascending necrotizing mediastinitis secondary to an emphysematous renal infection.

Systematic review of spontaneous pneumomediastinum: a survey of 22 years' data.

OBJECTIVE: To describe and clarify management protocols in relation to spontaneous pneumomediastinum, and try to integrate criteria on this subject. BACKGROUND: Thoracic physicians are faced with patients who present with gas in the mediastinum, frequently without an obvious etiologic factor. Published material contains heterogeneous information from which different conclusions can be drawn. METHODS: In a Medline search from 1990 to 2012, we collected data on mortality, morbidity, signs, symptoms, etiologic factors, and diagnostic methods. Standardized mean differences were calculated. RESULTS: We identified 600 patients in 27 papers with series of >5 patients without precipitating or etiologic factors previous to the clinical presentation, but athletic activity, drug abuse, and history of asthma played an apparent role in the disease process. Most patients complained of thoracic pain and dyspnea, with subcutaneous emphysema and Hamman's sign. The most common complication was tension pneumothorax. Morbidity was seen in 2.8%; no mortality has been reported so far. CONCLUSION: Spontaneous pneumomediastinum is a rare disease with a benign course, which should be treated conservatively unless a complication mandates an invasive procedure. An algorithm for diagnosis and treatment is offered, based on the available evidence.

Descending necrotizing mediastinitis below the tracheal carina.

BACKGROUND: Descending necrotizing mediastinitis is a dreadful disease with a high mortality rate, particularly when below the tracheal carina. This study describes the epidemiologic, clinical, and paraclinical features of patients treated for this condition. METHODS: We performed a single-center retrospective descriptive review of 60 patients with descending necrotizing mediastinitis below the tracheal carina, who were treated during a 7-year period, the largest study in the last 50 years. Demographic, clinical, paraclinical, and therapeutic variables were analyzed. RESULTS: 43 (71.7%) patients were male. The mean age was 41.2 ± 14.7 years. Mean hospital length of stay was 25.0 ± 19.8 days. Comorbidities were present in 46.7% of patients, diabetes mellitus being the most common. Odontogenic infections (45%) were the most frequent source of descending necrotizing mediastinitis. Cultures showed Gram-negative bacilli in 68.3%, Gram-positive cocci in 38.3%, and fungi in 6.7%. Mortality was 35% (21 patients); risk factors for mortality were age (>35 years), diabetes mellitus among other comorbidities, and associated complications. CONCLUSIONS: In this low socioeconomic status patient population, descending necrotizing mediastinitis below the carina causes high morbidity and mortality, the latter particularly associated with age, complications, diabetes mellitus and other comorbidities.