ABSTRACT
Acute myeloid leukemia (AML) is the most frequent indication for allogeneic hematopoietic cell transplantation (alloHCT) worldwide; social and health system barriers limit its access. We performed an observational retrospective analysis in Mexico to analyze factors limiting alloHCT in fit patients with AML. With a median follow-up of 11.8 months, 301 patients were included, with a median age of 42; 33.5% were classified as adverse risk. Despite 215 patients (92.5%) achieving complete remission, only 103 (34%) had HLA-typing: 44.5% had a matched-sibling donor (MSD), 32% a haploidentical donor, and 23.5% had no donor. Only 23.5% of patients had an HCT consult; merely 36 underwent an HCT: 30 alloHCT, and six an autologous HCT. Age ≥ 60 years, HCT-CI score ≥ three, and the absence of a local transplant program negatively influenced HLA typing likelihood. Patients with an MSD had a higher alloHCT likelihood. The cumulative incidence of transplant (CIT) and relapse (CIR) at 6 and 12 months was 7.3% and 13.8%, 8.2% and 13%, respectively. A lack of HLA-typing was associated with a lower CIT (p < 0.001) and higher CIR (p = 0.033) (HR 11.72, CI 95% 4.39-31.27, p < 0.001), while the presence of an MSD was associated with a higher CIT (p = 0.002) (HR 4.22, CI 95% 1.89-9.44, p < 0.001). The main reasons hindering alloHCT are the lack of access to HLA-typing tests and the absence of an MSD. A national donor registry and improved HLA-typing accessibility are critical for increasing alloHCT access in Mexico.
ABSTRACT
Cordycepin, or 3'-deoxyadenosine, is an adenosine analog with a broad spectrum of biological activity. The key structural difference between cordycepin and adenosine lies in the absence of a hydroxyl group at the 3' position of the ribose ring. Upon administration, cordycepin can undergo an enzymatic transformation in specific tissues, forming cordycepin triphosphate. In this study, we conducted a comprehensive analysis of the structural features of cordycepin and its derivatives, contrasting them with endogenous purine-based metabolites using chemoinformatics and bioinformatics tools in addition to molecular dynamics simulations. We tested the hypothesis that cordycepin triphosphate could bind to the active site of the adenylate cyclase enzyme. The outcomes of our molecular dynamics simulations revealed scores that are comparable to, and superior to, those of adenosine triphosphate (ATP), the endogenous ligand. This interaction could reduce the production of cyclic adenosine monophosphate (cAMP) by acting as a pseudo-ATP that lacks a hydroxyl group at the 3' position, essential to carry out nucleotide cyclization. We discuss the implications in the context of the plasticity of cancer and other cells within the tumor microenvironment, such as cancer-associated fibroblast, endothelial, and immune cells. This interaction could awaken antitumor immunity by preventing phenotypic changes in the immune cells driven by sustained cAMP signaling. The last could be an unreported molecular mechanism that helps to explain more details about cordycepin's mechanism of action.
Subject(s)
Cyclic AMP , Deoxyadenosines , Molecular Dynamics Simulation , Neoplasms , Deoxyadenosines/metabolism , Deoxyadenosines/pharmacology , Deoxyadenosines/chemistry , Humans , Neoplasms/metabolism , Neoplasms/drug therapy , Neoplasms/pathology , Cyclic AMP/metabolism , Adenosine Triphosphate/metabolism , Signal Transduction/drug effects , Computer Simulation , Adenylyl Cyclases/metabolismABSTRACT
Background and objective Frank's sign is the diagonal ear fold which has been associated with ischemic heart disease. The objective of this work was to evaluate the relationship of Frank's sign with severity of ischemic heart disease in adults ≤ 65 years old in the northeast of Mexico. Patients and methods A cross-sectional study was conducted in patients ≤ 65 years old who underwent coronary angiography consecutively over a period of 5 months in 2022. Severe coronary artery disease (CAD) was associated with Frank's sign and other common cardiovascular risks. To determine the association, bivariate and multivariate analysis was performed using logistic regression that included variables with a value of p<0.05. Statistical analysis was performed with SPSS version 22. Results We included 311 patients ≤ 65 years, of whom 80% were men. The median age was 57 years (range 2865). Frank's sign was positive in 62% of the population. The main clinical characteristics in patients with Frank's sign were type 2 diabetes mellitus (55%), p=0.003, dyslipidemia (53%), p=0.026 and smoking (68%), p=0.002. In the multivariate analysis, the independent variables associated with severe CAD were Frank's Sign OR 3.26; 95% CI (1.985.38), p≤0.001, male gender OR 2.28; 95% CI (1.204.35), p=0.012, and dyslipidemia OR 1.81; 95% CI (1.112.97), p=0.017. Conclusions There is an independent association between Frank's sign with the presence of severe CAD in patients ≤ 65 years old, which may be useful for screening and prevention (AU)
Antecedentes y objetivo El signo de pliegue diagonal de la oreja o signo de Frank se ha asociado con cardiopatía isquémica. El objetivo de este trabajo fue evaluar la relación del signo de Frank con la gravedad de la cardiopatía isquémica en adultos≤65años en el noreste de México. Pacientes y métodos Se realizó un estudio transversal en pacientes ≤65años sometidos a coronariografía de manera consecutiva en un periodo de 5 meses en 2022. Se relacionó la enfermedad arterial coronaria (EAC) grave con el signo de Frank y los factores de riesgo cardiovascular tradicionales. Para determinar la asociación se realizó análisis bivariado y multivariado mediante regresión logística que incluyó las variables con valor de p<0,05. El análisis estadístico se realizó con el programa SPSS versión 22. Resultados Se incluyeron 311 pacientes≤65años, de los cuales el 80% fueron hombres. La mediana de edad fue 57 años (rango de 28-65 años). El 62% de los pacientes presentó el signo de Frank. Las principales características clínicas en pacientes con signo de Frank fueron diabetes mellitus tipo 2 (55%), p=0,003, dislipidemia (53%), p=0,026 y tabaquismo (68%), p=0,002. En el análisis multivariado las variables independientes asociadas a EAC grave fueron el signo de Frank (OR: 3,26; IC 95%: 1,98-5,38; p≤0,001), sexo masculino (OR: 2,28; IC 95%: 1,20-4,35; p=0,012) y dislipidemia (OR: 1,81; IC 95%: 1,11-2,97; p=0,017). Conclusiones Existe asociación independiente del signo de Frank con la presencia de EAC grave en pacientes≤65años, que puede ser útil para el cribado y la prevención (AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Myocardial Ischemia/diagnostic imaging , Cross-Sectional Studies , Coronary Angiography , Risk Factors , PrognosisABSTRACT
Introduction Cardiac myxomas account for 50% of all benign cardiac tumors. Their clinical presentation varies from embolisms to fever. Our objective was to describe the surgical experience in the resection of cardiac myxomas during an 8-year period.MethodsThis is a retrospective, descriptive study of a series of cases with cardiac myxomas diagnosed from 2014 to 2022 at a tertiary care center. Descriptive statistics were used to define the populational and surgical characteristics. We used Pearsons correlation to study the relationship between postoperative complications and age, tumor size and affected cardiac chamber.Results31 patients were included, with a predominance of females (1:2 ratio). The prevalence was 0.44%, which was calculated based on the number of cardiac surgeries performed in our unit over the 8-year period. The main clinical manifestation was dyspnea (85%, n = 23), followed by cerebrovascular event (CVE) (18%, n = 5). Atriotomy and resection of the pedicle were performed with preservation of the interatrial septum. Mortality was 3.2%. The postoperative evolution was uneventful in 77%. Tumor recurrence occurred in 2 patients (7%), both debuting with embolic phenomena. No association was observed between postoperative complications or recurrence and tumor size, nor aortic clamping and extracorporeal circulation times with regard to age.ConclusionsFour atrial myxoma resections are performed in our unit per year, with an estimated prevalence of 0.44%. The tumor characteristics described coincide with the previous literature. A relationship between embolisms and recurrences cannot be ruled out. Wide surgical resection of the pedicle and base of tumor implantation may influence tumor recurrence, although further studies are needed. (AU)
Introducción Los mixomas cardíacos representan el 50% de los tumores cardíacos benignos. La presentación clínica varía desde embolismos hasta fiebre. El objetivo fue describir la experiencia quirúrgica en la resección de mixomas cardíacos durante 8 años.MétodosEstudio retrospectivo, descriptivo, de serie de casos de mixomas cardíacos diagnosticados entre 2014 y 2022 en un centro de tercer nivel. Se utilizó estadística descriptiva para definir las características poblacionales y quirúrgicas. Mediante la correlación de Pearson se estudió la relación entre las complicaciones postoperatorias y la edad, el tamaño del tumor y la cavidad cardiaca afectada.ResultadosSe incluyeron 31 pacientes, predominantemente mujeres (1:2). La prevalencia fue 0.44%, calculada en base a las cirugías cardíacas realizadas en nuestra unidad durante 8 años. La principal manifestación fue disnea (85%, n = 23), seguida de EVC (18%, n = 5). Se realizó atriotomía y resección del pedículo con preservación del tabique interauricular. La mortalidad fue del 3.2%. La evolución posquirúrgica fue adecuada en el 77%. La recidiva ocurrió en 2 pacientes (7%), debutando ambos con embolismos. No se observó asociación entre las complicaciones postoperatorias o recurrencia y el tamaño tumoral; ni en pinzamiento aórtico y los tiempos de circulación extracorpórea con respecto a la edad.ConclusionesEn nuestra unidad se realizan cuatro resecciones de mixoma auricular anuales (prevalencia de 0.44%). Las características tumorales descritas coinciden con la literatura previa. No se descarta relación entre embolismos y recurrencias. La resección amplia del pedículo y base del tumor puede influir en la recurrencia tumoral, aunque, se requieren más estudios. (AU)
Subject(s)
Humans , Male , Female , Myxoma , Thoracic Surgery , Embolism , Epidemiology, Descriptive , Retrospective Studies , Neoplasm Recurrence, LocalABSTRACT
En Colombia, el cáncer colorectal es reconocido como un importante problema de salud pública, con una tendencia general al incremento en ambos géneros; se ubica entre los cinco primeros lugares en relación con la mortalidad. Teniendo en cuenta los diagnósticos histopatológicos reunidos entre enero de 2000 y diciembre de 2007, se realizó un análisis descriptivo retrospectivo en 191 pacientes tolimenses con tumores colorrectales tipo adenocarcinoma; estos fueron seleccionados en cinco centros de patología de la ciudad de Ibagué, mediante pruebas descriptivas básicas empleando el método porcentual. Los datos más sobresalientes corresponden a la edad al momento del diagnóstico (promedio mayor de 60 años), localización en el recto (34,6%) y en el colon izquierdo (28,3%) y aumento de los adenomas tubulovelloso y velloso.
In Colombia, colorectal cancer is recognized as a major public health problem. Its general tendency is occur more frequently among both genders. It now ranks among the top five in terms of mortality. Using histopathological diagnoses collected from pathology laboratories in Ibagué, Tolima between January 2000 and December 2007, we conducted a retrospective analysis of 191 patients who had colorectal adenocarcinoma. The most important findings are that the average age of diagnosis was over 60 years, most common tumor locations were in the rectum (34.6%) and in the left colon (283%), and the greatest numbers of tumors were tubulovillous adenoma, or villous adenoma. Most of cases were tubular.