Description of a new quantitative method to assess mitochondrial distribution pattern in mature equine oocytes.

The Mitochondrial distribution pattern or MDP in mammalian oocytes serves as an indicator of their cytoplasmic maturity, with a heterogeneous pattern associated with mature cytoplasm. Currently, MDP assessment involves fluorescent labelling of mitochondria followed by visual evaluation, as no quantitative method exists. Our objective was to develop a quantitative approach to assess MDP in mature equine oocytes. Equine oocytes, obtained by ovum pick up (OPU) were matured in vitro, and only metaphase II oocytes were used in the study (n = 56). Following denudation, oocytes were fixed, stained with MitoTracker™ Red CMXRos (50 nM in TCM-199 with Hank´s salts and 10% FBS) for 15 min at 38 °C, and then incubated with 2.5 µg/ml Hoechst 33342 for 10 min at 38 °C. Confocal microscope images were acquired, and the oocyte's MDP was visually classified as either homogeneous (HoD; n = 17) or heterogeneous (HeD; n = 39). For quantitative analysis, Fiji-ImageJ software was employed. Background subtraction was performed, and a 1-pixel line along the diameter was drawn to calculate the intensity profile. Fluorescence intensities were normalized, and ratios of peripheral to central fluorescence intensity were determined. Student´s t-test was used for comparations; MDP ratio was (mean ± standard error of the mean): 0.8 ± 0.02 for HoD and 0.3 ± 0.02 for HeD (p < 0.001). These results demonstrate concordance between quantitative and qualitative MDP assessment in mature equine oocytes. Our study describes a new approach to quantify mitochondrial distribution pattern and cytoplasmic maturation in mature equine oocytes.

Use of Venetoclax in Patients with Relapsed or Refractory Acute Myeloid Leukemia: The PETHEMA Registry Experience.

The effectiveness of venetoclax (VEN) in relapsed or refractory acute myeloid leukemia (RR-AML) has not been well established. This retrospective, multicenter, observational database studied the effectiveness of VEN in a cohort of 51 RR-AML patients and evaluated for predictors of response and overall survival (OS). The median age was 68 years, most were at high risk, 61% received ≥2 therapies for AML, 49% had received hypomethylating agents, and ECOG was ≥2 in 52%. Complete remission (CR) rate, including CR with incomplete hematological recovery (CRi), was 12.4%. Additionally, 10.4% experienced partial response (PR). The CR/CRi was higher in combination with azacitidine (AZA; 17.9%) than with decitabine (DEC; 6.7%) and low-dose cytarabine (LDAC; 0%). Mutated NPM1 was associated with increased CR/CRi. Median OS was 104 days (95% CI: 56-151). For the combination with AZA, DEC, and LDAC, median OS was 120 days, 104 days, and 69 days, respectively; p = 0.875. Treatment response and ECOG 0 influenced OS in a multivariate model. A total of 28% of patients required interruption of VEN because of toxicity. Our real-life series describes a marginal probability of CR/CRi and poor OS after VEN-based salvage. Patients included had very poor-risk features and were heavily pretreated. The small percentage of responders did not reach the median OS.

Outcome of patients treated with palliative weekly paclitaxel plus cetuximab in recurrent head and neck cancer after failure of platinum-based therapy.

Few therapeutic options are available for recurrent/metastatic head and neck cancer when progression occurs after initial chemotherapy. We analyzed retrospectively the efficacy of weekly Paclitaxel plus Cetuximab as second line of palliative chemotherapy. Patients with squamous carcinoma of head and neck with documented progression after initial treatment were enrolled. Tumor response was evaluated through the response evaluation criteria in solid tumor criteria. The retrospective analysis focused on overall survival (OS) and progression-free survival (PFS). Between 2008 and 2011, 33 consecutive patients were treated. A response rate of 55% was observed, with median response duration of 5.0 months (95% CI 3.3-11.1). The median PFS was 4.0 months (95% CI 2.9-5.0) and the median OS time was 10.0 months (95% CI 7.9-12.0). Acne-like rash/Folliculitis and chronic anemia were the most common adverse events. A weekly schedule of Paclitaxel plus Cetuximab is a promising regimen for patients with advanced head and neck cancer after failure of platinum-based therapy. Good tolerance of this treatment suggests that would be used in fragile patients.

Dihydropyrimidine dehydrogenases and cytidine-deaminase gene polymorphisms as outcome predictors in resected gastric cancer patients treated with fluoropyrimidine adjuvant chemotherapy.

BACKGROUND AND OBJECTIVES: Single nucleotide polymorphisms of dihydropyrimidine dehydrogenases gene (DPYD) induces dihydropyrimidine dehydrogenase enzyme (DPD) deficiency resulting in increased activity of 5-fluorouracil derivatives. Cytidine-deaminase gene (CDA) polymorphisms have been involved in prognosis in experimental tumours. METHODS: Analysis of 50 consecutive resected gastric cancer patients who received adjuvant chemotherapy with Tegafur for polymorphisms of genes DPYD1 (A/G; Ile543Val), DPYD2 (C/T; Arg29Cys) and CDA (A/C; Lys27Gin). The status of alleles (wild-type or at least one polymorphism) was correlated with outcome and toxicity. RESULTS: Polymorphisms frequencies wild-type/non-wild-type were 36/14 in DPYD1 (A/G; Ile543Val); 26/24 in DPYD2 (C/T; Arg29Cys); and 17/23 in CDA (A/C; Lys27Gin) or between homozygous/heterozygous were 39/11 in DPYD1; 33/17 in DPYD2 and 26/24 in CDA respectively. After 77 months of median follow-up (SD = 26.3), 18 patients died of tumour relapse. Better survival was observed in DPYD1 patients only, for non-wild-type over wild-type (P = 0.0214); and in patients with one or more heterozygous polymorphisms in any of the three genes tested (P = 0.0017). In 10 pts (20%) total dose was reduced by toxicity, only 3 of them were homozygous. CONCLUSIONS: Gene polymorphisms of DPYD and CDA predict survival of gastric cancer patients treated with 5-fluorouracil-based adjuvant chemotherapy.

[Analysis of arrhythmias in immediate post-operative period of cardiovascular surgery]. / Análisis de las arritmias en el postoperatorio inmediato de cirugía cardiovascular.

Cardiac arrhythmias are one of the most frequent complications in the immediate post-operatory period of cardiac surgery with extracorporeal circulation, this occurring in between 35% and 50% of the patients subjected to this therapeutic intervention. Among the causal factors, electrolytic alterations, direct surgical aggression on the heart tissue and alterations secondary to ischemic cell damage that is produced in the myocardial during extracorporeal circulation are found. Due to the frequency of appearance of arrhythmias, we decided to study them and know them in depth. Thus, the objective of our study was to know the incidence and prevalence of arrhythmias during the immediate post-operatory period of cardiovascular surgery. Out of all those admitted to the unit, all the patients who had undergone valvular and coronary surgery with a stay in the intensive care unit of the University Hospital Marques de Valdecilla that did not exceed 7 days were selected. This means 258 patients, the most frequent alterations during the post-operative period being right branch blockage (16%), atrial fibrillation (12%), ventricular tachycardy (7%), atrial ventricular block (4%), among other rhythm and conduction alterations. As conclusions, we stress that the most frequent alterations during the immediate post-operative period were branch blocks, arrhythmia being more prevalent than atrial fibrillation. A total of 85% of the patients undergoing valvular replacement and 89% of those operated on for coronary derivation plus valvular replacement had more arrhythmia episodes than the rest.

Análisis de las arritmias en el postoperatorio inmediato de cirugía cardiovascular / Analysis of arhythmias in immediate post-operative period of cardiovascular surgery

Las arritmias cardíacas son una de las complicaciones más frecuentes en el postoperatorio inmediato de cirugía cardíaca con circulación extracorpórea, y se presentan entre el35 y el 50% de los pacientes sometidos a esta intervención terapéutica. Entre los factores causales se encuentran las alteraciones electrolíticas, la agresión quirúrgica directa sobre el tejido cardíaco y las alteraciones secundarias al daño celular isquémico que se produce en el miocardio durante la circulación extracorpórea. Debido a la frecuencia de aparición de las arritmias, decidimos estudiarlas y conocerlas a fondo, por ello el objetivo de nuestro estudio fue conocer la incidencia y prevalencia de las arritmias durante el postoperatorio inmediato de cirugía cardiovascular. Del total de ingresos en la unidad de cuidados intensivos (DCI) del Hospital Universitario Marqués de Valdecilla, se seleccionaron a todos los pacientes a los que se les había realizado cirugía valvular y coronaría con una estancia en la unidad no superior a 7 días. En total fueron 258 pacientes, y las alteraciones más frecuentes durante el postoperatorio fueron: bloqueo de rama derecha (16%), fibrilación auricular (12%), taquicardia ventricular (7%), bloqueo auriculoventricular (4%), entre otras alteraciones del ritmo y de la conducción. Destacamos como conclusiones que las alteraciones más frecuentes durante el postoperatorio inmediato fueron los bloqueos de rama, y la arritmia más prevalente fue la fibrilación auricular. El 85% de los pacientes sometidos a recambio valvular y el 89% de los intervenidos de cirugía de derivación coronaría más recambio valvular tuvieron más episodios de arritmias que el resto

Cardiac arhythmias are one of the most frequent complications in the immediate post-operatory period of cardiac surgery with extracorporeal circulation, this occurring in between 35% and 50% of the patients subjected to this therapeutic intervention. Among the causal factors, electrolytic alterations, direct surgical aggression on the heart tissue and alterations secondary to ischemic cell damage that is produced in the myocardial during extracorporeal circulation are found. Due to the frequency of appearance of arhythmias, we decided to study them and know them in depth. Thus, the objective of our study was to know the incidence and prevalence of arhythmias during the immediate post-operatory period of cardiovascular surgery. Out of all those admitted to the unit, all the patients who had undergone valvular and coronary surgery with a stay in the intensive care unit of the University Hospital Marques de Valdecilla that did not exceed 7 days were selected. This means 258 patients, the most frequent alterations during the post-operative period being right branch blockage (16%), atrial fibrillation (12%), ventricular tachycardy (7%), atrial ventricular block (4%), among other rhythm and conduction alterations. As conclusions, we stress that the most Irequent alterations during the immediate post-operative period were branch blocks, arhythmia being more prevalent than atrial fibrillation. A total 0185% of the patients undergoing valvular replacement and 89% of those operated on for coronary derivation plus valvular replacement had more arhythmia episodes than the rest