Hydrogels in the Treatment of Degenerative Tendinopathy / Hidrogeles en el Tratamiento de la Tendinopatía Degenerativa

Abstract: Degenerative tendinopathy is a significant health problem, and its incidence increases yearly. This condition causes functional deficits in young and adult patients and sedentary or active individuals, resulting in health, social, and economic consequences. Due to limited blood supply, drug administration is complex for tendon diseases, such as degenerative tendinopathy. Biomaterials, such as hydrogels, have gained significant attention in designing drug delivery systems to treat musculoskeletal pathologies due to their attractive characteristics and the challenges posed by conventional drug delivery routes. This paper provides an overview of tendon pathology and discusses the use of hydrogels as drug carriers and release agents in emerging treatments.

Resumen: La tendinopatía degenerativa es un importante problema de salud, y su incidencia aumenta cada año en todo el mundo. Esta condición genera déficits funcionales en pacientes jóvenes o adultos, así como en personas sedentarias o activas, trayendo consigo repercusiones sanitarias, sociales y económicas. Debido al suministro de sangre limitado, la administración de medicamentos es compleja para las enfermedades de los tendones, como la tendinopatía degenerativa. El uso de biomateriales, como los hidrogeles, ha ganado una atención significativa en el diseño de sistemas de administración de fármacos para tratar patologías musculoesqueléticas debido a sus atractivas características y los desafíos que plantean las rutas convencionales de administración de fármacos. Este documento proporciona una descripción general de la patología del tendón y analiza el uso de hidrogeles como transportadores de fármacos y agentes de liberación en tratamientos emergentes.

The link between lymphocyte subpopulations in peripheral blood and metabolic variables in patients with severe obesity.

Background: Obesity, a public health problem, is a state of metainflammation that influences the development of chronic degenerative diseases, particularly in patients with severe obesity. Objective: The objective of this study was to evidence immunometabolic differences in patients with different degrees of obesity, including severe obesity, by determining correlations between lymphocyte subpopulations and metabolic, body composition, and clinical variables. Methods: Peripheral blood immune cells (CD4+, CD8+ memory and effector T lymphocytes) were analyzed, and measures of body composition, blood pressure, and biochemical composition (glucose, glycated hemoglobin (HbA1c), insulin, C-reactive protein (CRP), and the lipid profile) were carried out in patients with different degrees of obesity. Results: The patients were classified according to total body fat (TBF) percentage as normal body fat, class 1 and 2 obesity, class 3 obesity, and class 4 obesity. The greater the TBF percentage, the more pronounced the differences in body composition (such as a decrease in the fat-free mass (FFM) that is defined as sarcopenic obesity) and the immunometabolic profile. There was an increase of CD3+ T lymphocytes (mainly CD4+, CD4+CD62-, and CD8+CD45RO+ T lymphocytes) and an increase in the TBF percentage (severity of obesity). Conclusions: The correlations between lymphocyte subpopulations and metabolic, body composition, and clinical variables demonstrated the existence of a chronic, low-intensity inflammatory process in obesity. Therefore, measuring the immunometabolic profile by means of lymphocyte subpopulations in patients with severe obesity could be useful to determine the severity of the disease and the increased risk of presenting obesity-associated chronic degenerative diseases.

Factores de riesgo para complicaciones graves de COVID-19, comparando tres olas epidemiológicas. Un enfoque desde la atención primaria en México / Risk factors for COVID-19 severe complications comparing three major epidemiological waves: An approach from primary health care in Mexico

Objetivos: Describir la asociación entre las enfermedades crónicas no transmisibles y la edad, con la hospitalización, desenlaces clínicos graves y las defunciones por COVID-19 en los casos confirmados en población mexicana, comparando las tres primeras olas epidemiológicas de la pandemia en México. Diseño: Se realizó un análisis transversal utilizando el Sistema de Vigilancia Epidemiológica de Enfermedad Respiratoria Viral para COVID-19. Emplazamiento: Sistema de Vigilancia Epidemiológica de Enfermedad Respiratoria Viral en México (SISVER). Participantes: Población mexicana confirmada para SARS-CoV-2 registrada en el SISVER. Mediciones principales: Los desenlaces graves analizados fueron hospitalización, neumonía, necesidad de ventilación mecánica, ingreso a la UCI y defunción. Se evaluó la asociación (odds ratio [OR]) entre los desenlaces y las variables clínicas, comparando las tres olas epidemiológicas en México. Resultados: Una edad mayor de 65 años se asocia a un mayor porcentaje de hospitalización, neumonía, y notablemente, con el total de defunciones, independientemente del efecto de las comorbilidades crónicas. Existe interacción entre la edad en conjunto con la obesidad, la cual se asocia con la hospitalización y neumonía. Estos hallazgos fueron consistentes a lo largo de las tres olas epidemiológicas.Conclusión: La obesidad, EPOC y la diabetes en interacción con la edad se asocian con peores desenlaces clínicos, primordialmente con defunciones en los pacientes con COVID-19.(AU)

Objectives: To describe the association between chronic noncommunicable diseases and age with hospitalization, death and severe clinical outcomes for COVID-19 in confirmed cases within the mexican population, comparing the first three epidemiological waves of the pandemic in Mexico. Design: We performed an analysis using Mexico's Government Epidemiological Surveillance System database for COVID-19. Emplacement: Mexico's Epidemiological Surveillance System for Respiratory Diseases. Participants: Mexican population confirmed with SARS-CoV-2 registered on Mexico's Epidemiological Surveillance System for Respiratory Diseases. Primary measurements: The analysed severe outcomes were hospitalization, pneumonia, use of mechanical ventilation, intensive care unit admission and death. The association (odds ratio) between the outcomes and clinical variables was evaluated, comparing the three epidemiological waves in Mexico. Results: Age over 65 is associated with a higher ratio of hospitalization and pneumonia, independent of the effect of chronic comorbidities. There is an interaction between age and obesity, which is associated with hospitalization, pneumonia and highly associated with death. These findings were consistent throughout the three epidemiological waves. Conclusion: Obesity, COPD and diabetes in interaction with age, are associated with worse clinical outcomes and, more importantly, death in patients with COVID-19.(AU)

[Risk factors for COVID-19 severe complications comparing three major epidemiological waves: An approach from primary health care in Mexico]. / Factores de riesgo para complicaciones graves de COVID-19, comparando tres olas epidemiológicas. Un enfoque desde la atención primaria en México.

OBJECTIVES: To describe the association between chronic noncommunicable diseases and age with hospitalization, death and severe clinical outcomes for COVID-19 in confirmed cases within the mexican population, comparing the first three epidemiological waves of the pandemic in Mexico. DESIGN: We performed an analysis using Mexico's Government Epidemiological Surveillance System database for COVID-19. EMPLACEMENT: Mexico's Epidemiological Surveillance System for Respiratory Diseases. PARTICIPANTS: Mexican population confirmed with SARS-CoV-2 registered on Mexico's Epidemiological Surveillance System for Respiratory Diseases. PRIMARY MEASUREMENTS: The analysed severe outcomes were hospitalization, pneumonia, use of mechanical ventilation, intensive care unit admission and death. The association (odds ratio) between the outcomes and clinical variables was evaluated, comparing the three epidemiological waves in Mexico. RESULTS: Age over 65 is associated with a higher ratio of hospitalization and pneumonia, independent of the effect of chronic comorbidities. There is an interaction between age and obesity, which is associated with hospitalization, pneumonia and highly associated with death. These findings were consistent throughout the three epidemiological waves. CONCLUSION: Obesity, COPD and diabetes in interaction with age, are associated with worse clinical outcomes and, more importantly, death in patients with COVID-19.

Immunologic Responses in Biological and Mechanical Valve Prostheses: Inflammation and Functionality Are Not Always Related.

BACKGROUND AND AIM OF THE STUDY: The aim of this retrospective study was to evaluate the inflammatory response in patients with aortic and/or mitral prostheses, and to correlate the level of inflammatory markers with prosthesis functionality. METHODS: A total of 48 patients with biological or mechanical prostheses was included in the study, in which levels of tumor necrosis factor-alpha (TNFα), interleukin (IL)-1, -4, and -6, interferon-gamma (IFNγ), osteopontin (OPN), intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), endothelin-1 and C-reactive protein were analyzed. Functionality of the prosthesis was evaluated using transthoracic echocardiography at three years after surgery. RESULTS: The mean period from the date of surgery was seven years. High levels of IL-1 were found in patients with mechanical prostheses compared to those with bioprostheses (p = 0.04). Patients with aortic bioprostheses and stenosis had higher levels of OPN and endothelin-1, those with aortic mechanical prostheses with stenosis had increased levels of matrix metalloproteinase (MMP)-9, OPN and ICAM, and those with aortic mechanical leakage had increased levels of MMP-1 and endothelin-1. In mitral bioprostheses with leakage of endothelin-1, ICAM and MMP-9 levels were increased, while in mechanical prostheses with leakage there were increases of ICAM and endothelin-1. Tricuspid bioprostheses with double lesions had increased levels of OPN and endothelin-1. CONCLUSIONS: Valvular dysfunction was similar across the types of prosthesis material. IL-1 was increased in subjects with mechanical prostheses independently of dysfunction, while in biological prostheses there were increases in OPN and endothelin-1, and these were related to valvular dysfunction. Given that in the analysis of durability and functionality there were no significant differences between biological and mechanical prostheses, biological prostheses may represent the first treatment option in patients with low economic resources, the elderly, and even young patients.

Pre- and post-surgical evaluation of the inflammatory response in patients with aortic stenosis treated with different types of prosthesis.

BACKGROUND: The inflammatory process in aortic valvular stenosis persists after surgery to replace the valve in almost half of the patients. No association has been found to its persistence. The main objective of this study was to evaluate the inflammatory response in patients with aortic stenosis through the determination of several biomarkers in plasma measured before and after the valvular replacement and to seek an association with the type of prosthesis used. METHODS: This is an observational study with a follow up of 6 months in subjects with severe aortic stenosis. Seric concentrations of TNFa, IL-1, IL-6 and ICAM and echocardiographic variables were quantified previous to the surgery and a week and 6 months after it. A group of control subjects paired by age and gender was included. RESULTS: Seventy-nine subjects were studied of which 57% were male; the average age was of 59 (± 11.4) years. Previous to surgery, the concentration of cytokines was higher in patients than in control subjects. A biological prosthesis was implanted in 48 patients and a mechanical prosthesis in 31. Both, types of prosthesis have components made of titanium. The echocardiograms 1 week and 6 months after the surgery showed a decrease in the mean aortic gradient and an increase in the valvular area (p = 0.001). Half of the patients still showed high proinflammatory cytokine levels. There were no differences according to the type of prosthesis implanted after adjustments for demographic variables, comorbidities and echocardiographic data. CONCLUSIONS: The inflammatory response caused by both types of valvular prothesis at 6 months after implantation were similar. Both types of prosthesis are recommended, they had similarities in hemodynamic profiles registered with Doppler echocardiography. Age of the patient or the suitability use of anticoagulants determines the type of prosthesis to be used.

Echocardiographic study of a Mestizo-Mexican population with Marfan syndrome.

BACKGROUND: The cardiovascular manifestations of Marfan syndrome (MFS) are the main causes of morbidity and mortality. This study describes the clinical and echocardiographic findings in a Mestizo-Mexican population affected by the disease. METHODS: A total of 166 patients previously diagnosed with MFS were recruited for the study, 114 of them underwent complete clinical history, with emphasis on Ghent nosology criteria, and transthoracic echocardiography, with 68 patients also undergoing transesophageal study. RESULTS: Major cardiovascular criteria from the Ghent nosology predominated in adults (P < 0.0001), minor criteria in children (P = 0.007). Among pediatric patients, 83% had a New York Heart Association (NYHA) functional class of I; however, 64% of the adult patients had an NYHA class ≥II, (P < 0.0001). Corrected aortic echocardiographic measurements of both groups demonstrated statistically significant differences. Children had a greater prevalence of mitral valve prolapse, while adults more frequently presented with aortic complications. Seven patients died during follow-up from aortic complications, one child and six adults. CONCLUSIONS: Based on the data, we can conclude that MFS in the Mestizo-Mexican population has a distinctly different clinical pattern in children and adults, and a graver prognosis in adults. Adult patients with MFS are significantly more likely, than children, to have aortic dilation, aortic aneurysm, aortic regurgitation, aneurysm rupture, aortic dissection, and fatal outcome. Children with MFS are more likely, than adults, to present with asymptomatic mitral and tricuspid prolapse and mitral valve regurgitation.

[C-reactive protein: cardiovascular issues of an acute-phase protein]. / Proteína C reactiva: aspectos cardiovasculares de una proteína de fase aguda.

C-reactive protein (CRP) is a nonspecific acute phase protein that has been used as an inflammatory marker for decades. More recently, it has been proposed as a predictor of cardiovascular disease (myocardial infarction, stroke, peripheral artery disease and sudden heart death). Physiologic functions of CRP as an anti-inflammatory scavenger molecule have begun to emerge. CRP binds to damaged lipoproteins and facilitates their removal by phagocytes, partially activating the complement cascade. Increased levels of CRP may result in direct effects on vascular cells, including the induction of cytokines and prothrombotic factors. Although previous studies suggested a potent independent association of CRP levels with cardiac events, the strength of this association has been shown to be weaker than previously reported in a recent large meta-analysis and in prospective studies. Therapy with statins in patients with coronary artery disease has been found to reduce adverse outcomes in association with reductions of CRP levels, independently of their effects on the lipid profile.

Proteína C reactiva: aspectos cardiovasculares de una proteína de fase aguda / C-reactive protein: cardiovascular issues of an acute-phase protein

C-reactive protein (CRP) is a nonspecific acute phase protein that has been used as an inflammatory marker for decades. More recently, it has been proposed as a predictor of cardiovascular disease (myocardial infarction, stroke, peripheral artery disease and sudden heart death). Physiologic functions of CRP as an anti-inflammatory scavenger molecule have begun to emerge. CRP binds to damaged lipoproteins and facilitates their removal by phagocytes, partially activating the complement cascade. Increased levels of CRP may result in direct effects on vascular cells, including the induction of cytokines and prothrombotic factors. Although previous studies suggested a potent independent association of CRP levels with cardiac events, the strength of this association has been shown to be weaker than previously reported in a recent large meta-analysis and in prospective studies. Therapy with statins in patients with coronary artery disease has been found to reduce adverse outcomes in association with reductions of CRP levels, independently of their effects on the lipid profile.

Determinación de la producción de interleucina-1B al estímulo mecánico en osteoblastos humanos cultivados "in vitro" / Determination of the interleukin-1B production by mechanical stimulation in cultured human osteoblastos, in vitro

La remodelación mecánica del hueso es utilizada por los ortodoncistas, quienes ejercen fuerza sobre los dientes para moverlos a través del hueso alveolar; tal remodelación ósea involucra la activación de las células del hueso y la estimulación de la reabsorción y aposición de la matriz ósea. La estimulacion mecánica ha sido reconocida como un factor importante en la remodelación ósea, especialmente durante la erupción de los dientes, en la corrección de las maloclusiones, sin embargo, los aspectos moleculares que se involucran en estos procesos no han sido totalmente entendidos. Se han desarrollado diferentes métodos para aplicar el estímulo mecánico al tejido óseo, in vivo o in vitro, a células humanas, para evaluar el resultado bioquímico. El objetivo de este trabajo fue analizar los efectos de la estimulación mecánica en osteoblastos humanos (Saos-2) cultivados in vitro, con respecto a la producción de interleucina 1 Beta (IL-1B), uno de los pasos involucrados en el proceso de remodelación ósea. En este estudio se desarrolló un método de crecer osteoblastos humanos como línea celular en cajas Petri, donde la base puede ser deformada intermitentemente cada 5 segundos después de 1.5 minutos durante más de 72 horas. La estimulación mcánica de estas células se compara con células no estimuladas (n=5). Los osteoblastos humanos son sembrados para ser confluentes en un medio de cultivo F12 de Dulbeco modificado con un 10 por ciento de suero fetal, 100 ug/mL de estreptomicina, 100U/mL de penicilina y 0.25 ug/mL de anfotericina, en una atmósfera de 95 por ciento de aire y un 5 por ciento de CO2, a 37§C. Utilizando el ensayo de ELISA (Enzyme-linked Immunoassay) se determinó los niveles de producción de IL-1B después de 8, 24, 48 y 72 horas. Los resultados mostraron que no hubo producción de IL-1B después de 8, 24, 48 y 72 horas. Los resultados mostraron que no hubo producción de IL-1B a las 8 horas de estímulo, sin embargo a las 24 (13.5 +- 2.1), 48 (23.2 +- 1.3) y 72 horas (33.9 +- 1.9) se encontró una diferencia estadísticamente significativa comparada con el control (p<0.0001). Estos resultados sugirieron que los osteoblastos humanos cutivados in vitro reaccionan al estímulo mecánico liberando mayor cantidad de IL-1B en comparación con el control y de alguna manera algunos efectos celulares pueden asociarse con la remodelación ósea y el movimiento dentario durante el tratamiento de ortodoncia