Vertical transmission of maternal DNA through extracellular vesicles associates with altered embryo bioenergetics during the periconception period.

The transmission of DNA through extracellular vesicles (EVs) represents a novel genetic material transfer mechanism that may impact genome evolution and tumorigenesis. We aimed to investigate the potential for vertical DNA transmission within maternal endometrial EVs to the pre-implantation embryo and describe any effect on embryo bioenergetics. We discovered that the human endometrium secretes all three general subtypes of EV - apoptotic bodies (ABs), microvesicles (MVs), and exosomes (EXOs) - into the human endometrial fluid (EF) within the uterine cavity. EVs become uniformly secreted into the EF during the menstrual cycle, with the proportion of different EV populations remaining constant; however, MVs contain significantly higher levels of mitochondrial (mt)DNA than ABs or EXOs. During the window of implantation, MVs contain an eleven-fold higher level of mtDNA when compared to cells-of-origin within the receptive endometrium, which possesses a lower mtDNA content and displays the upregulated expression of mitophagy-related genes. Furthermore, we demonstrate the internalization of EV-derived nuclear-encoded (n)DNA/mtDNA by trophoblast cells of murine embryos, which associates with a reduction in mitochondrial respiration and ATP production. These findings suggest that the maternal endometrium suffers a reduction in mtDNA content during the preconceptional period, that nDNA/mtDNA become packaged into secreted EVs that the embryo uptakes, and that the transfer of DNA to the embryo within EVs occurs alongside the modulation of bioenergetics during implantation.

Influencia de la edad en el pronóstico a corto y largo plazo del choque cardiogénico de origen isquémico / Influence of age in short and long term prognostic of ischemic cardiogenic shock

Objetivo: Comparar la evolución durante el ingreso y a largo plazo de pacientes con choque cardiogénico de origen isquémico. Método: Estudio observacional prospectivo unicéntrico llevado a cabo en la unidad coronaria de un hospital terciario manejada por cardiólogos. Se incluyen pacientes con choque cardiogénico de origen isquémico que recibieron revascularización coronaria precoz. Dividimos a los pacientes en 2 grupos: mayores de 75 anos (grupo A) y menores (grupo B), y comparamos la evolución durante el ingreso y en un seguimiento máximo de 4 años. El objetivo principal fue estimar la mortalidad a los 4 años. El objetivo secundario se definió como la mortalidad intrahospitalaria. Resultados: Incluimos a 97 pacientes, 44 del grupo A (45%). Los pacientes del grupo B eran con más frecuencia varones (81 vs. 57%, p = 0.014), diabéticos (49 vs. 21%, p: 0.006) y fumadores (39.6 vs. 4.5%, p < 0.05). La mortalidad hospitalaria fue superior en el grupo A (54.5 vs. 30.2%, p = 0.022). El objetivo principal ocurrió en 32 pacientes del grupo A frente a 20 del grupo B (73 vs. 38%, p = 0.007). Conclusión: El choque cardiogénico de origen isquémico en paciente mayores de 75 anos presenta una alta mortalidad durante la estancia hospitalaria y en el seguimiento a largo plazo.

Objective: To compare the prognosis during hospitalization and maximum follow-up of 4 years in patients with myocardial infarction complicated with cardiogenic shock. Method: Prospective observational study practiced in a coronary Care Unit managed by cardiologists. We included patients with myocardial infarction complicated with cardiogenic shock who received early coronary revascularization. Patients were divided into two groups: older than 75 years (group A) and lower (group B), and we compared the evolution during hospitalization and maximum follow-up of 4 years. Primary end point was mortality rate in the maximum follow-up of 4years. Secondary end point was mortality rate during hospitalization. Results: Ninety-seven patients were included, 45% Group A. Patients of Group B were mostly men (81% vs. 57%; P =.014), diabetics (48% vs. 21%; P = 0.006), and smokers (39.6% vs. 5%). Mortality rate during hospitalization was higher in Group A (54.5%) vs. 30.2% in Group B(P = .022). Mortality rate during follow-up (primary variable) was 73% in Group A vs. 38% in Group B (P =.007). Conclusions: Myocardial infarction complicated with cardiogenic shock in elderly patients is an entity with high mortality during hospitalization and continues to worsen during long term follow-up.

Analyzing SNOMED CT and HL7 terminology binding for semantic interoperability on post-genomic clinical trials.

Current post-genomic clinical trials in cancer involve the collaboration of several institutions. Multi-centric retrospective analysis requires advanced methods to ensure semantic interoperability. In this scenario, the objective of the EU funded INTEGRATE project, is to provide an infrastructure to share knowledge and data in post-genomic breast cancer clinical trials. This paper presents the process carried out in this project, to bind domain terminologies in the area, such as SNOMED CT, with the HL7 v3 Reference Information Model (RIM). The proposed terminology binding follow the HL7 recommendations, but should also consider important issues such as overlapping concepts and domain terminology coverage. Although there are limitations due to the large heterogeneity of the data in the area, the proposed process has been successfully applied within the context of the INTEGRATE project. An improvement in semantic interoperability of patient data from modern breast cancer clinical trials, aims to enhance the clinical practice in oncology.

[Clinical-pathological study of incidental renal cell carcinoma]. / Estudio clinico-patologico de los adenocarcinomas renales incidentales.

OBJECTIVES: To determine the percentage of renal cell carcinomas incidentally diagnosed (IRCC) and to compare their clinical and pathological characteristics with symptomatic or non-incidentally diagnosed tumors (SRCC). METHODS: We retrospectively study 189 patients who were diagnosed of renal carcinoma between 1990 and 1999. 166 underwent surgery (149 radical nephrectomy; 17 nephron-sparing surgery). We determine the percentage of IRCC detected by radiological tests and compare them with the SRCC diagnosed after presenting with some of the classic symptoms or metastasis, with special focus on tumor size, pathology stage, tumor recurrence, progression and evolution. RESULTS: 87 SRCC (46%); 102 SRCC (54%). There are not differences in terms of age, gender, side, and postoperative hospital stay. Tumor size was higher in the SRCC (mean 8.5 cm) than in the IRCC (6.3 cm). SRCC tumor stage was: pT1 27.3%, pT2 27.3%, pT3a 23.8%, pT3b 16.6%, pT3c 2.3%, and pT4 2.3%; IRCC stage was: pT1 51.3%, pT2 25.6%, pT3a 10.9%, pT3b 10.9%, pT3c 1.2%, and no pT4. The percentage of patients with lymph node involvement was higher (p = 0.02) in the SRCC (15%) than in the IRCC (4.8%). The percentage of patients with metastasis at the time of diagnosis was higher in the SRCC group (26%) than in the IRCC (9.2%). Recurrences were more frequent in the SRCC Group (8.3%) than in the IRCC (1.2%) (p = 0.07). Tumor progression was more frequent in the SRCC group (34%) than in the IRCC (7.3%) (p<0.01). 76% of the patients undergoing nephron sparing surgery were IRCC. CONCLUSIONS: Currently, there is a high percentage of IRCC (46% in our series from 1990-99). Renal tumors presenting as IRCC have better prognosis, since they have significantly smaller size, lower stage, less advanced disease, less recurrences, and less progression than SRCC.

[Cutaneous metastasis of a renal carcinoma: case report and review]. / Metastasis cutánea del cáncer renal: caso clínico y revisión.

OBJECTIVES: To report another rare case of skin metastasis from a renal adenocarcinoma, analyzing the prognostic significance, response to therapy, and clinical presentation after a bibliographic review. METHODS/RESULTS: We report the case of a 65-year-old male with a cutaneous metastasis in the root of his inferior left extremity one year after right nephrectomy for a clear cell adenocarcinoma. CONCLUSIONS: Skin metastases usually present as solitary cutaneous lesions of variable macroscopic features and rapid growing; the diagnosis is made by histological analysis, being excision the treatment of choice whenever possible. Prognosis is better for solitary lesions appearing asynchronously with the primary tumor, and among them the longer the time after diagnosis of initial lesion they appear the better the prognosis.

[Staging of infiltrating bladder cancer. Role of C.T. scan]. / Estadiaje del cáncer de vejiga infiltrante. Papel de la T.A.C.

OBJECTIVES: To analyse the role of CT-scan on preoperative determination of bladder and lymph node involvement of infiltrative bladder cancer, and its possible impact on the surgical management of these patients. METHODS: Retrospective study including 115 patients with the diagnosis of infiltrative bladder cancer between 1984 and 1999. The ability of CT-scan for bladder and lymph node staging was evaluated comparing results with the findings after radical surgery. Potential impact of this imaging technique on change of surgical attitudes was evaluated. RESULTS: Perivesical involvement estimation by CT-scan was right in 36.5%, underestimated in 49.6% and overestimated in 14%. The more advanced the perivesical involvement the lower the sensitivity for CT-scan in perivesical staging. The more locally advanced tumour the higher specificity, oscillating between 44% for pT2 and 94% for pT4. In reference to lymph node staging, it was correct in 71.3% of the cases, although this percentage depended almost exclusively on patients with negative nodes (N-). However, there was a 24.3% understaging rate which corresponded to the majority of N+ patients. These data offer a 28% sensitivity, 93% specificity, 68% positive predictive value, and 72% negative predictive value. Finally, the reliability of bladder staging in patients with lymph node involvement (N+) (39 patients) was established; it was correctly estimated in as low as 30% of the cases with a 70% understaging rate. CT-scan would have modified surgical attitudes in only 6 patients (5%), all of them with advanced tumours. CONCLUSIONS: The impact of CT-scan on infiltrative bladder cancer clinical staging is relatively low. The highest benefit is obtained in patients suspect of having advanced disease. Limitation to this group would result in significative cost reductions with low risk for unappropriate surgical management.

[Bladder choriocarcinoma: retrospective analysis of the de-differentiation of a transitional-cell papillary bladder carcinoma. Apropos of a case]. / Coriocarcinoma vesical; análisis retrospectivo de la desdiferenciación de un carcinoma vesical papilar de células transicionales a propósito de un caso.

OBJECTIVE: To report a case of choriocarcinoma of the bladder during the different periods of its evolution. The anatomopathological study showing dedifferentiation of a transitional cell tumor is presented and the histogenesis of this rare tumor is discussed. METHODS: A case of a rapidly progressing transitional cell tumor of the bladder that dedifferentiated into choriocarcinoma is presented. The pathological findings of the first resections of the transitional cell tumor that progressed to choriocarcinoma are presented and the histogenesis is discussed. RESULTS/CONCLUSIONS: Choriocarcinoma of the bladder is very rare, highly malignant and carries a poor prognosis. Its origin is widely accepted to be in the dedifferentiation of a transitional cell tumor. The use of immunohistochemistry and the positivity of HCG support the diagnosis.

[Ureteroplasty using the appendix: apropos of a case]. / Ureteroplastia con apéndice: a propósito de un caso.

OBJECTIVE: To report a case of ureteroplasty using the vermiform appendix. METHODS: Herein we describe a patient who underwent partial resection of the ureter due to a neoplasm. The ureteral defect was repaired using the vermiform appendix. The surgical technique and the results achieved are presented and the literature is briefly reviewed. RESULTS/CONCLUSIONS: The few cases reported in the literature and the case described herein show the utility of the vermiform appendix for ureteral substitution in specific cases where this procedure is indicated.